nature publishing group VOLUME 109 SUPPLEMENT 1 AUGUST 2014 S2 The American Journal ofGASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 |AUGUST 2014www.amjgastro.com see related editorial on page x Irritable bowel syndrome (IBS) and chronic idiopathic constipa- tion ((CIC) also reerred to as unctional constipation) are two othe most common unctional gastrointestinal disorders world- wide. IBS is a global problem, with anywhere rom 5 to 15 % othe general population experiencing symptoms that would satisy a denition oIBS (1,2). In a systematic review on the global preva- lence oIBS, Lovell and Ford ( 1) documented a po oled prevalence o11% with all regions othe world suffering rom this disorder at similar rates. Given its prevalence, the requency osymptoms, and their associated debility or many patients and the act that IBS typically occurs in younger adulthood, an important period or urthering education, embarking on careers, and /or raising amilies, the socioeconomic impact oIBS is considerable. Tese indirect medical costs are requently compounded by the direct medical costs related to additional medical tests and the use ovarious medi cal and nonmedical remedi es that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford (3) reported a pooled prevalence o14%, and also noted that constipation was more common in emales, in older subjects, and those olower socioeconomic status ( 3). Chronic constipation has also been linked to impaired quality olie ( 4), most notably among the elderly (5). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, thereore, on clinical grounds. Although a number oclinical denitions oboth IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, thereore, most relevant to any review othe literature on the management othese disorders. According to Rome III, IBS is dened on the basis othe pres- ence of:Recurrent abdominal pain or discomort at least 3 days /month in the past 3 months associated with two or more othe ollowing: Improvement with deecation Onset associated with a change in requency ostool Onset associated with a change in orm (appearance) ostool Tese criteria should be ullled or the past 3 months with symptom onset at least 6 months beore diagnosis ( 6). Rome III denes unctional constipation as: the presence otwo or more othe ollowing: Straining during at least 25 % odeecations Lumpy or hard stools in at least 25 % odeecations Sensation oincomplete evacuation or at least 25 % odeeca- tions Sensation oanorectal obstruction/blockage or at least 25% odeecations Manual maneuvers to acilitate at least 25 % odeecations (e.g., digital evacuation, suppo rt ot he pelvic oor) Fewer than three deecations per week Furthermore, loose stools are rarely present without the use olaxatives and there are insufficient criteria or IBS. Again, t hese criteria should be ullled or the past 3 months with symptom onset at least 6 months beore diagnosis ( 6). In Rome III, IBS is subtyped according to predominant bowel habit as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), and unclassied (IBS-U). Te denition o• • • • • • • • • American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation Alexander C. Ford, MB ChB, MD, FRCP 1 , 10 , Paul Moayyedi, BSc, MB ChB, PhD, MPH, FACG 2 , 11 , Brian E. Lacy, MD, PhD, FACG 3 , Anthony J. Lembo, MD 4 , Yuri A. Saito, MD, MPH 5 , Lawrence R. Schill er , MD, FACG 6 , Edy E. Soffer , MD, FACG 7 , Brennan M.R. Spiegel, MD, FACG 8 and Eamonn M.M. Quigley , MD, FACG 9 , for the Task Force on the Management of Functional Bowel Disorders Am J Gastr oenterol2014; 109:S2–S26; doi:10.1038/ajg.2014.187 1 Leeds Gastroenterology Institute, St James ’ s University Hospital, Leeds, UK; 2 Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada; 3 Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire, USA; 4 Harvard Medical School, Beth Israel Deaconess Medical Center , Boston, Massachusetts, USA; 5 Mayo Clinic, Rochester, Minnesota, USA; 6 Baylor University Medical Center, Digestive Health Associates of Texas, Dallas, Texas, USA; 7 Division of Gastroenterology, Keck School of Medicine, University of Southern California , Los Angeles, California, USA; 8 UCLA School of Medicine, UCLA /VA Center for Outcomes Research and Education (CORE) , Los Angeles, California, USA; 9 Division of Gastroenterology and Hepatology , Houston Methodist Hospital and Weill Cornell Medical College , Houston, Texas, USA; 10 First author on the monograph, but is not a member of the Task Force; 11 Conducted systematic reviews with the support of A.C. Ford, and carried out the technical analyses of the data independent of the Task Force . Correspondence: Eamonn M.M. Quigley, MD, FACG, Chief, Division of Gastroenterolog y & Hepatology , Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA. E-mail: e.quigley@ucc .ie CME
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
nature publishing groupVOLUME 109 SUPPLEMENT 1 AUGUST 2014S2
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
see related editorial on page x
Irritable bowel syndrome (IBS) and chronic idiopathic constipa-
tion ((CIC) also reerred to as unctional constipation) are two
o the most common unctional gastrointestinal disorders world-wide IBS is a global problem with anywhere rom 5 to 15 o the
general population experiencing symptoms that would satisy a
de1047297nition o IBS (12) In a systematic review on the global preva-
lence o IBS Lovell and Ford (1) documented a pooled prevalence
o 11 with all regions o the world suffering rom this disorder
at similar rates Given its prevalence the requency o symptoms
and their associated debility or many patients and the act that
IBS typically occurs in younger adulthood an important period
or urthering education embarking on careers andor raising
amilies the socioeconomic impact o IBS is considerable Tese
indirect medical costs are requently compounded by the direct
medical costs related to additional medical tests and the use o various medical and nonmedical remedies that may have limited
impact CIC is equally common in another systematic review
Suares and Ford (3) reported a pooled prevalence o 14 and also
noted that constipation was more common in emales in older
subjects and those o lower socioeconomic status (3) Chronic
constipation has also been linked to impaired quality o lie (4)
most notably among the elderly (5)
Neither IBS nor CIC are associated with abnormal radiologic
or endoscopic abnormalities nor are they associated with a
reliable biomarker diagnosis currently rests entirely thereore
on clinical grounds Although a number o clinical de1047297nitions
o both IBS and CIC have been proposed the criteria developed
through the Rome process currently in its third iteration havebeen those most widely employed in clinical trials and thereore
most relevant to any review o the literature on the management
o these disorders
According to Rome III IBS is de1047297ned on the basis o the pres-
ence of
Recurrent abdominal pain or discomort at least 3 daysmonthin the past 3 months associated with two or more o the ollowing
Improvement with deecation
Onset associated with a change in requency o stool
Onset associated with a change in orm (appearance) o stool
Tese criteria should be ul1047297lled or the past 3 months with
symptom onset at least 6 months beore diagnosis (6)
Rome III de1047297nes unctional constipation as the presence o
two or more o the ollowing
Straining during at least 25 o deecationsLumpy or hard stools in at least 25 o deecations
Sensation o incomplete evacuation or at least 25 o deeca-
tions
Sensation o anorectal obstructionblockage or at least 25
o deecations
Manual maneuvers to acilitate at least 25 o deecations
(eg digital evacuation support o the pelvic 1047298oor)
Fewer than three deecations per week
Furthermore loose stools are rarely present without the use
o laxatives and there are insuffi cient criteria or IBS Again these
criteria should be ul1047297lled or the past 3 months with symptom
onset at least 6 months beore diagnosis (6)In Rome III IBS is subtyped according to predominant bowel
habit as IBS with constipation (IBS-C) IBS with diarrhea (IBS-D)
mixed type (IBS-M) and unclassi1047297ed (IBS-U) Te de1047297nition o
bull
bull
bull
bullbull
bull
bull
bull
bull
American College of Gastroenterology Monograph on
the Management of Irritable Bowel Syndrome andChronic Idiopathic Constipation
Alexander C Ford MB ChB MD FRCP1 10 Paul Moayyedi BSc MB ChB PhD MPH FACG2 11 Brian E Lacy MD PhD FACG3 Anthony J Lembo MD4 Yuri A Saito MD MPH5 Lawrence R Schiller MD FACG6 Edy E Soffer MD FACG7 Brennan MR SpiegelMD FACG8 and Eamonn MM Quigley MD FACG9 for the Task Force on the Management of Functional Bowel Disorders
Am J Gastroenterol 2014 109S2ndashS26 doi101038ajg2014187
1 Leeds Gastroenterology Institute St Jamesrsquos University Hospital Leeds UK 2 Farncombe Family Digestive Health Research Institute Division of GastroenterologyMcMaster University Hamilton Ontario Canada 3 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire USA 4 Harvard Medical School BethIsrael Deaconess Medical Center Boston Massachusetts USA 5 Mayo Clinic Rochester Minnesota USA 6 Baylor University Medical Center Digestive HealthAssociates of Texas Dallas Texas USA 7 Division of Gastroenterology Keck School of Medicine University of Southern California Los Angeles California USA8 UCLA School of Medicine UCLA VA Center for Outcomes Research and Education (CORE) Los Angeles California USA 9 Division of Gastroenterology andHepatology Houston Methodist Hospital and Weill Cornell Medical College Houston Texas USA 10 First author on the monograph but is not a member of theTask Force 11 Conducted systematic reviews with the support of AC Ford and carried out the technical analyses of the data independent of the Task ForceCorrespondence Eamonn MM Quigley MD FACG Chief Division of Gastroenterology amp Hepatology Houston Methodist Hospital and Weill Cornell MedicalCollege Houston Texas USA E-mail equigleyuccie
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Lubiprostone is superior to placebofor the treatment of IBS-C
Strong Moderate 3 3 3 Expensive
There is no evidence that poly-ethylene glycol improves overall
symptoms and pain in patientswith IBS
Weak Very low Not clear whetherthis intervention is
effective
Not clear whether thisintervention is effective and
hence although adverseevents are rare cannotevaluate risks vs benefits
3 Can be moderatelyexpensive for
patients
GI gastrointestinal GRADE Grading of Recommendations Assessment Development and Evaluation 5-HT3 serotonin subtype 3 5-HT
4 serotonin subtype 4
IBS irritable bowel syndrome IBS-C IBS with constipation IBS-D IBS with diarrhea NNH number needed to harm SSRI selective serotonin reuptake inhibitorTCA tricyclic antidepressanta Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis ( 289) has shown there is lesscertainty that the drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those with milder
symptomsb Check marks indicate that the criterion was fulfilled not a concern
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
Linaclotide is effective in CIC 3 1582 084 (080ndash087) 6 (5ndash8) Strong High
Lubiprostone is effective in the treatment of CIC 4 651 067 (058ndash077) 4 (3ndash6) Strong High
Biofeedback is effective in CIC patients withdemonstrated evidence of pelvic floor dyssynergia
3 216 033 (022ndash050) 2 (16ndash4) Weak Low
CI confidence interval CIC chronic idiopathic constipation NNT number needed to treat PEG polyethylene glycol RR relative risk
Table 5 Reasons for quality of evidence of assessment of data on CIC according to GRADE criteria
Statement
Quality
assessment Study limitations Inconsistency
Indirectness
of evidence Imprecision Reporting bias
Some fiber supplementsincrease stool frequency in
patients with CIC
Low All trials were unclearrisk of bias but did
show a marked effect
End points different evenin the studies that could be
combined
3 a Only a smallnumber of patients
studied
Not evaluable
PEG is effective in increasingstool frequency and improv-ing stool consistency in CIC
High All RCTs low risk ofbias and demonstratedstrong treatment effect
Moderate heterogeneitybetween studies
3 3 Not evaluable
Lactulose is effective inincreasing stool frequencyand improving stoolconsistency in CIC
Low Both trials at high riskof bias but there was astrong treatment effect
Moderate heterogeneitybetween studies
3 Only a smallnumber of patientsstudied with wide95 CIs
Not evaluable
Sodium picosulfate andbisacodyl are effective inCIC
Moderate Both trials low risk ofbias and strong treat-ment effect
Significant heterogeneitybetween studies
3 Modest number ofpatients studied foreach intervention
Not evaluable
Prucalopride is moreeffective than placebo atimproving symptoms of CIC
Moderate 5 8 Trials were low riskof bias and these stud-ies were also positive
Significant heterogeneitybetween studies that wasunexplained
3 3 3
Linaclotide is effective inCIC
High 3 3 3 3 3
Lubiprostone is effective inthe treatment of CIC
High Two trials low risk ofbias strong treatmenteffect
3 3 3 Not evaluable
Biofeedback is effective inCIC patients with demon-strated evidence of pelvicfloor dyssynergia
Low All three trials werehigh risk of bias butthe treatment effectwas marked
End points different evenin the studies that could becombined and interventionslightly different betweenstudies
3 Very modestnumber of patientsstudied
Not evaluable
CI confidence interval CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG poly-ethylene glycol RCT randomized controlled triala Check marks indicate that the criterion was fulfilled not a concern
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
In the largest study to date 275 patients o whom 53ndash58 wereIBS-C and 19ndash29 were IBS-D were randomized to one o three
arms 10 g o the soluble 1047297ber psyllium 10 g o the insoluble 1047297ber
bran or 10 g o a placebo once daily or 12 weeks (57) During the
1047297rst month a signi1047297cantly greater proportion o patients receiv-
ing psyllium but not bran reported adequate symptom relie or
at least 2 weeks compared with placebo (57 vs 35 psyllium vs
placebo RR 160 95 CI 113ndash226) Bran was more effective than
placebo during the third month o treatment only (57 vs 32
170 112ndash257) Afer 3 months o treatment symptom severity
in the psyllium group was reduced by 90 points compared with
49 points in the placebo group (P = 003) and 58 points in the
bran group (P = 061 vs placebo) No differences were ound with
respect to quality o lie Dropout was most common in the brangroup most commonly because o exacerbation in IBS
Data on overall adverse events were only provided by six trials
(575860646569) Tese trials evaluated 566 patients but as
numbers o adverse events were so small in 5 o the trials pooling
o data was not carried out A total o 130 (388) o 335 patients
receiving 1047297ber reported adverse events compared with 63 (273)
o 231 in the placebo arms
Summary Although its use in the management o IBS is time
honored the status o 1047297ber in general in IBS is ar rom straight-
orward Insoluble 1047297bers may exacerbate symptoms and provide
little relie soluble 1047297bers and psyllium in particular provide relie
in IBS Tese latter effects appear to transcend expected bene1047297ts interms o relie o constipation
3 Interventions that modify the microbiota probiotics prebiotics
and antibiotics
Te suggestion that the gut bacteria could be relevant to IBS
1047297rst came rom the observation that a small although de1047297nite
proportion o individuals who suffer an episode o bacterial
gastroenteritis will go on to develop IBS de novo postinec-
tious IBS (70) Although bacterial ermentation has been linked
to bloating and 1047298atulence and changes in the microbiota have
been described in IBS the contribution o the microbiota to
these or other symptoms in IBS is unclear Tus although both
small intestinal bacterial overgrowth (SIBO) (71) and quantita-tive and qualitative changes in the ecal microbiota (72) have
also been linked to IBS (73) the overall contribution o SIBO to
IBS remains controversial (74) and 1047297ndings in relation to the
microbiota require con1047297rmation in larger patient populations
Prebiotics probiotics and prebioticndashprobiotic preparations
have been used or decades on an empirical basis by IBS suffer-
ers they have only recently been subjected to scrutiny in clini-
cal trials Te interpretation o probiotic studies in IBS remains
challenging as studies have employed different species strains
preparations and doses in various patient populations and ofen
in substandard trials
Table 6 Reasons for strength of recommendation for treatments of CIC according to GRADE criteria
Statement
Recommen-
dation
Quality of
evidence
All patient
groups Benefits vs risks Patient values Costa
Some fiber supplements increase stoolfrequency in patients with CIC
Strong Low 3 b Fiber can cause bloatingand abdominal discomfort
Some patients donot like taking fiber
supplements
3
PEG is effective in increasing stoolfrequency and improving stoolconsistency in CIC
Strong High 3 3 3 Can be expensiveto patients
Lactulose is effective in increasingstool frequency and improving stoolconsistency in CIC
Strong Low 3 Lactulose can causebloating
3 3
Sodium picosulfate and bisacodyl areeffective in CIC
Strong Moderate 3 3 3 3
Prucalopride is more effective thanplacebo at improving symptoms of CIC
Strong Moderate 3 3 3 Expensive
Linaclotide is effective in CIC Strong High 3 3 3 Expensive
Lubiprostone is effective in the treatmentof CIC
Strong High 3 3 3 Expensive
Biofeedback is effective in CIC patientswith demonstrated evidence of pelvicfloor dyssynergia
Weak Low 3 3 Some patients notreceptive to the ideaof biofeedback
Expensive
CIC chronic idiopathic constipation GRADE Grading of Recommendations Assessment Development and Evaluation PEG polyethylene glycola Cost was classified as expensive for the health service if the listed medication cost was gt $5 per day At this level an economic analysis (289) has shown thereis less certainty that drug is cost effective although it is important to emphasize that this will be cost effective for some patients but may not be for those withmilder symptomsb Check marks indicate that the criterion was fulfilled not a concern
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
20 Ford et al
We identi1047297ed 3 RCs o the bile acid transporter inhibitor A3309
in CIC involving 256 patients (283ndash285) All three trials were at
low risk o bias Varying doses o A3309 were employed ranging
rom as low as 01 mg to as high as 20 mg Responses were dose
dependent In the largest study to date (283) an increase o ge 1
complete spontaneous bowel movements per week over baseline
or 4 o the 8 weeks o the study was reported or 58 64 and 75
o those randomized to 5 10 and 15 mg o A3309 respectively
compared with 33 or placebo
Diarrhea was more common in the patients receiving A3309
compared with placebo (RR = 262 95 CI 072ndash956)
7 Probiotics in CIC
Tere is insuffi cient evidence to recommend probiotics in CIC
Recommendation weak Quality of evidence very low
We identi1047297ed three trials evaluating probiotics in 245 CIC patients
(286ndash288) None o the eligible trials stated the method o randomi-
zation or concealment and one was an open design In two trials(286288) the risk o bias was deemed to be unclear and one (287)
had a high risk o bias Tere were two trials (286287) that reported
on improvement in constipation in 110 CIC patients Although both
trials were positive in avor o probiotics improving constipation
the pooled data were not statistically signi1047297cant (RR = 029 95 CI
007ndash112) in a random effects model as there was signi1047297cant heter-
ogeneity between the two trials Tere were two trials (287288) that
reported on mean number o bowel movements per week in 165
patients Tere was a signi1047297cant improvement in the mean number
o bowel movements per week (mean increase in bowel movements
per week in the symbiotic group = 149 95 CI 102ndash196)
CONFLICT OF INTEREST
Guarantor of the article Eamonn MM Quigley MD FACG
Speci1047297c author contributions AC Ford and P Moayyedi perormed
the meta-analyses and participated in writing and reviewing the
manuscript EMM Quigley BE Lacy YA Saito LR Schiller EE
Soffer BMR Spiegel and AJ Lembo together with P Moayyedi
developed all grading and recommendations and contributed to writ-
ing the manuscript All authors reviewed all drafs o the manuscript
and agreed with the 1047297nal version AC Ford is 1047297rst author on the
monograph but is not a member o the ask Force P Moayyedi
conducted systematic reviews with support o AC Ford and carried
out the technical analyses o the data independent o the ask Force
Financial support Unrestricted grants have been provided to theAmerican College o Gastroenterology rom Forest Laboratories
Ironwood Pharmaceuticals Nestleacute Health Science and Prometheus
Laboratories Te analysis that supports this monograph and its
writing were conducted on behal o the American College o
Gastroenterology and the ACG Institute or Clinical Research amp
Education by the ACG Functional Bowel Disorders ask Force
which had complete scienti1047297c and editorial control o its content and
whose work was supported exclusively by the ACG Institute Readers
should note that the work o the systematic review was conducted
and the writing o the IBSCIC monograph was completed beore
unding was obtained
Potential competing interests AC Ford has received grantresearch
support rom Almirall and GE Healthcare and is a consultant
speaker or Almirall GE Healthcare Mayoly Spindler Merck Sharp
amp Dohme and Shire Pharmaceuticals BE Lacy has served on
scienti1047297c advisory boards or Ironwood Pharmaceuticals akeda
Salix and Prometheus is a consultant to Furiex and receives grant
support rom the NIH or the unctional dyspepsia treatment trial
YA Saito has received research unding rom P1047297zer and Ironwood
Pharmaceuticals and is on the advisory board o Salix LR Schiller
has served on the speakersrsquo bureau or Forest Laboratories Iron-
wood Pharmaceuticals AbbottAbbvie akeda Salix and Santarus
Pharmaceuticals EE Soffer has served as a consultant and share-
holder or EndoStim BMR Spiegel has received grant support rom
akeda Ironwood Pharmaceuticals Teravance Amgen Shire and
Nestleacute Health Sciences is an advisor to Astellas and received con-
sulting ees rom Ironwood Pharmaceuticals and lecture ees rom
akeda EMM Quigley has served as a consultant andor on the
advisory board or Salix Almirall Ironwood Pharmaceuticals For-
est Laboratories ShireMovetis Janssen Rhythm PharmaceuticalsVibrant and Alimentary Health has served as a speaker or Procter
amp Gamble Almirall Janssen Alimentary Health and Shire has
received research support rom Rhythm Alimentary Health Vibrant
Pharma and Norgine and has been a non-executive director share-
holder and patent holder or Alimentary Health P Moayyedi has
served as a speaker or AstraZeneca Shire and Forest Laboratories
Canada has served as consultant andor on the advisory board or
Forest Laboratories Canada and his Chair at McMaster University
is unded in part by an unrestricted donation rom AstraZeneca to
McMaster University AJ Lembo has served as a consultant andor
on the advisory board or Ironwood Pharmaceuticals Forest Labora-
tories Salix Prometheus AstraZeneca and Furiex and has receivedresearch support rom Prometheus and Furiex
REFERENCES1 Lovell RM Ford AC Global prevalence o and risk actors or irritable bowel
syndrome a meta-analysis Clin Gastroenterol Hepatol 201210712ndash212 Quigley EM Abdel-Hamid H Barbara G et al A global perspective on
irritable bowel syndrome a consensus statement o the World Gastro-enterology Organisation Summit ask Force on Irritable Bowel SyndromeJ Clin Gastroenterol 201246356ndash66
3 Suares NC Ford AC Prevalence o and risk actors or chronic idiopathicconstipation in the community systematic review and meta-analysisAm J Gastroenterol 20111061582ndash91
4 Belsey J Green1047297eld S Candy D et al Systematic review impact o constipa-tion on quality o lie in adults and children Aliment Pharmacol Ter201031938ndash49
5 Koloski NA Jones M Wai R et al Impact o persistent constipation onhealth-related quality o lie and mortality in older community-dwellingwomen Am J Gastroenterol 20131081152ndash8
6 Longstreth GF Tompson WG Chey WD et al Functional bowel disordersGastroenterology 20061301480ndash91
7 Lewis SJ Heaton KW Stool orm scale as a useul guide to intestinal transittime Scand J Gastroenterol 199732920ndash4
8 Whitehead WE Engel B Schuster MM Irritable bowel syndrome physio-logical and psychological differences between diarrhea-predominant andconstipation-predominant patients Dig Dis Sci 198025404ndash13
9 Wouters MM Lambrechts D Knapp M et al Genetic variants in CDC42and NXPH1 as susceptibility actors or constipation and diarrhoeapredominant irritable bowel syndrome Gut 2014631103ndash11
10 Hughes PA Harrington AM Castro J et al Sensory neuro-immune inter-actions differ between irritable bowel syndrome subtypes Gut 201362 1456ndash65
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
11 Olasdottir LB Gudjonsson H Jonsdottir HH et al Irritable bowel syn-drome physiciansrsquo awareness and patientsrsquo experience World J Gastroen-terol 2012183715ndash20
12 Brandt LJ Bjorkman D Fennerty MB et al Systematic review on the man-agement o irritable bowel syndrome in North America Am J Gastroen-terol 200297 (11 Suppl) S7ndashS26
13 Brandt LJ Prather CM Quigley EM et al Systematic review on the man-agement o chronic constipation in North America Am J Gastroenterol
2005100 (Suppl 1) S5ndashS2114 Shekhar C Monaghan PJ Morris J et al Rome III unctional constipation
and irritable bowel syndrome with constipation are similar disorders withina spectrum o sensitization regulated by serotonin Gastroenterology2013145749ndash57
15 Wong RK Palsson O urner MJ et al Inability o the Rome III criteria todistinguish unctional constipation rom constipation-subtype irritablebowel syndrome Am J Gastroenterol 20101052228ndash34
16 Zhao YF Ma XQ Wang R et al Epidemiology o unctional constipationand comparison with constipation-predominant irritable bowel syndromeTe Systematic Investigation o Gastrointestinal Diseases in China (SILC)Aliment Pharmacol Ter 2011341020ndash9
17 Brandt LJ Chey WD Foxx-Orenstein AE et al An evidence-basedsystematic review on the management o irritable bowel syndrome Am JGastroenterol 2009104 (Suppl I) S8ndashS35
18 Ford AC alley NJ Spiegel BMR et al Effect o 1047297bre antispasmodics andpeppermint oil in irritable bowel syndrome systematic review and meta-analysis BMJ 20083371388ndash92
19 Ford AC Brandt LJ Young C et al Effi cacy o 5-H3 antagonists and 5-H
4
agonists in irritable bowel syndrome systematic review and meta-analysisAm J Gastroenterol 20091041831ndash43
20 Ford AC alley NJ Schoeneld PS et al Effi cacy o antidepressants andpsychological therapies in irritable bowel syndrome systematic review andmeta-analysis Gut 200958367ndash78
21 Ford AC Suares NC Effect o laxatives and pharmacological therapies inchronic idiopathic constipation systematic review and meta-analysis Gut201160209ndash18
22 Moayyedi P Ford AC Brandt LJ et al Te effi cacy o probiotics in thetreatment o irritable bowel syndrome a systematic review Gut 201059325ndash32
23 Manning AP Tompson WG Heaton KW et al owards positive diagnosiso the irritable bowel BMJ 1978277653ndash4
24 Kruis W Tieme CH Weinzierl M et al A diagnostic score or the irritable
bowel syndrome Its value in the exclusion o organic disease Gastro-enterology 1984871ndash7
25 Drossman DA Tompson WG alley NJ Identi1047297cation o sub-groups ounctional gastrointestinal disorders Gastroenterology Intl 19903159ndash72
26 Tompson WG Longstreth GF Drossman DA et al Functional boweldisorders and unctional abdominal pain Gut 199945 (Suppl II) II43ndash7
27 Higgins JP Green S Cochrane handbook or systematic reviews ointerventions Version 502 wwwcochrane-handbookorg 2009
28 Dersimonian R Laird N Meta-analysis in clinical trials Control Clin rials19867177ndash88
29 Higgins JP Tompson SG Deeks JJ et al Measuring inconsistency inmeta-analyses BMJ 2003327557ndash60
30 Egger M Davey-Smith G Schneider M et al Bias in meta-analysis detectedby a simple graphical test BMJ 1997315629ndash34
31 Sterne JA Sutton AJ Ioannidis JP et al Recommendations or examiningand interpreting unnel plot asymmetry in meta-analyses o randomisedcontrolled trials BMJ 2011343d4002
32 Guyatt G Oxman AD Akl EA et al GRADE guidelines 1 Introduction-GRADE evidence pro1047297les and summary o 1047297ndings tables J Clin Epidemiol201164383ndash94
33 Balshem H Heland M Schunemann HJ et al GRADE guidelines 3 Rat-ing the quality o evidence J Clin Epidemiol 201164401ndash6
34 Simren M Mansson A Langkilde AM et al Food-related gastrointestinalsymptoms in the irritable bowel syndrome Digestion 200163108ndash15
35 Rona RJ Keil Summers C et al Te prevalence o ood allergy a meta-analysis J Allergy Clin Immunol 2007120638ndash46
36 Lack G Epidemiologic risks or ood allergy J Allergy Clin Immunol20081211331ndash6
37 Bhat K Harper A Gorard DA Perceived ood and drug allergies inunctional and organic gastrointestinal disorders Aliment Pharmacol Ter200216969ndash73
38 Young E Stoneham MD Petruckevitch A et al A population study o oodintolerance Lancet 19943431127ndash30
39 Heizer WD Southern S McGovern S Te role o diet in symptoms oirritable bowel syndrome in adults a narrative review J Am Diet Assoc20091091204ndash14
40 Monsbakken KW Vandvik PO Farup PG Perceived ood intolerance insubjects with irritable bowel syndrome--etiology prevalence and conse-quences Eur J Clin Nutr 200660667ndash72
41 Halpert A Dalton CB Palsson O et al What patients know about irritablebowel syndrome (IBS) and what they would like to know National Survey
on Patient Educational Needs in IBS and development and validation othe Patient Educational Needs Questionnaire (PEQ) Am J Gastroenterol20071021972ndash82
42 Hayes P Corish C OrsquoMahony E et al A dietary survey o patients with ir-ritable bowel syndrome J Hum Nutr Diet 201427 (Suppl 2) 36ndash47
43 Atkinson W Sheldon A Shaath N et al Food elimination based on IgGantibodies in irritable bowel syndrome a randomised controlled trial Gut2004531459ndash64
44 Biesiekierski JR Newnham ED Irving PM et al Gluten causes gastroin-testinal symptoms in subjects without celiac disease a double-blind rand-omized placebo-controlled trial Am J Gastroenterol 2011106508ndash14
45 King S Elia M Hunter JO Abnormal colonic ermentation in irritablebowel syndrome Lancet 19983521187ndash9
46 Ong DK Mitchell SB Barrett JS et al Manipulation o dietary short chaincarbohydrates alters the pattern o gas production and genesis o symptomsin irritable bowel syndrome J Gastroenterol Hepatol 2010251366ndash73
47 Staudacher HM Lomer MC Anderson JL et al Fermentable carbohydraterestriction reduces luminal bi1047297dobacteria and gastrointestinal symptomsin patients with irritable bowel syndrome J Nutr 20121421510ndash8
48 Bentley SJ Pearson DJ Rix KJ Food hypersensitivity in irritable bowelsyndrome Lancet 19832295ndash7
49 Carroccio A Brusca I Mansueto P et al Fecal assays detect hypersensitivityto cowrsquos milk protein and gluten in adults with irritable bowel syndromeClin Gastroenterol Hepatol 20119965ndash71
50 Shepherd SJ Parker FC Muir JG et al Dietary triggers o abdominalsymptoms in patients with irritable bowel syndrome randomizedplacebo-controlled evidence Clin Gastroenterol Hepatol 20086765ndash71
51 Vazquez Roque MI Camilleri M Smyrk et al A controlled trial ogluten-ree diet in patients with irritable bowel syndrome-diarrhea effectson bowel requency and intestinal unction Gastroenterology 2013144903ndash11
52 Halmos EP Power VA Shepherd SJ et al A diet low in FODMAPs reducessymptoms o irritable bowel syndrome Gastroenterology 201414667ndash75
53 Biesiekierski JR Peters SL Newnham ED et al No effects o gluten inpatients with sel-reported non-celiac gluten sensitivity afer dietaryreduction o ermentable poorly absorbed short-chain carbohydratesGastroenterology 2013145320ndash8
54 Berg LK Fagerli E Martinussen M et al Effect o ructose-reduced diet inpatients with irritable bowel syndrome and its correlation to a standardructose breath test Scand J Gastroenterol 201348936ndash43
55 Moayyedi P Quigley EM Lacy BE et al Te effect o 1047297ber supplementationon irritable bowel syndrome A systematic review and meta-analysisAm J Gastroenterol 2014 (in press)
56 Arthurs Y Fielding JF Double blind trial o ispaghulapoloxamer in theirritable bowel syndrome Ir Med J 198376253
57 Bijkerk CJ de Wit NJ Muris JW et al Soluble or insoluble 1047297bre in irritablebowel syndrome in primary care Randomised placebo controlled trialBMJ 2009339b3154
58 Fowlie S Eastwood MA Prescott R Irritable bowel syndrome assessmento psychological disturbance and its in1047298uence on the response to 1047297bresupplementation J Psychosom Res 199236175ndash80
59 Jalihal A Kurian G Ispaghula therapy in irritable bowel syndromeimprovement in overall well-being is related to reduction in boweldissatisaction J Gastroenterol Hepatol 19905507ndash13
60 Kruis W Weinzierl M Schussler P et al Comparison o the therapeuticeffects o wheat bran mebeverine and placebo in patients with the irritablebowel syndrome Digestion 198634196ndash201
61 Longstreth GF Fox DD Youkeles L et al Psyllium therapy in the irritablebowel syndrome a double-blind trial Ann Intern Med 19819553ndash6
62 Lucey MR Clark ML Lowndes JO et al Is bran effi cacious in irritablebowel syndrome A double blind placebo controlled crossover study Gut198728221ndash5
63 Manning AP Heaton KW Harvey RF et al Wheat 1047297bre and irritable bowelsyndrome a controlled trial Lancet 1977310417ndash8
64 Nigam P Kapoor KK Rastog CK et al Different therapeutic regimens inirritable bowel syndrome J Assoc Physicians India 1984321041ndash4
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
22 Ford et al
65 Prior A Whorwell P Double blind study o ispaghula in irritable bowelsyndrome Gut 1987281510ndash3
66 Rees G Davies J Tompson R et al Randomised-controlled trial o a 1047297bresupplement on the symptoms o irritable bowel syndrome J R Soc Health200512530ndash4
67 Ritchie JA ruelove SC reatment o irritable bowel syndrome withlorazepam hyoscine butylbromide and ispaghula husk BMJ 1979278376ndash8
68 Soltof J Krag B Gudmand-Hoyer E et al A double-blind trial o theeffect o wheat bran on symptoms o irritable bowel syndrome Lancet1976307270ndash2
69 Cockerell KM Watkins AS Reeves LB et al Effects o linseeds on thesymptoms o irritable bowel syndrome a pilot randomised controlledtrial J Hum Nutr Diet 201225435ndash43
70 Halvorson HA Schlett CD Riddle MS Postinectious irritable bowelsyndrome--a meta-analysis Am J Gastroenterol 20061011894ndash9
71 Lin HC Small intestinal bacterial overgrowth a ramework or under-standing irritable bowel syndrome JAMA 2004292852ndash8
72 Jeffrey IB Quigley EM Ohman L et al Te microbiota link to irritablebowel syndrome an emerging story Gut Microbes 20123572ndash6
73 Spiegel BM Questioning the bacterial overgrowth hypothesis in irritablebowel syndrome an epidemiologic and evolutionary perspective ClinGastroenterol Hepatol 20119461ndash9
74 Ford AC Spiegel BMR alley NJ et al Small intestinal bacterial over-growth in irritable bowel syndrome systematic review and meta-analysisClin Gastroenterol Hepatol 200971279ndash86
75 Pimentel M Chow EJ Lin HC Eradication o small intestinal bacterialovergrowth reduces symptoms o irritable bowel syndrome Am J Gastro-enterol 2000953503ndash6
76 Menees SB Maneerattanaporn M Kim HM et al Te effi cacy and saety oriaximin or the irritable bowel syndrome a systematic review and meta-analysis Am J Gastroenterol 201210728ndash35
77 Silk DB Davis A Vulevic J et al Clinical trial the effects o a trans-galac-tooligosaccharide prebiotic on aecal microbiota and symptoms in irritablebowel syndrome Aliment Pharmacol Ter 200929508ndash18
78 Min YW Park SU Jang YS et al Effect o composite yogurt enrichedwith acacia 1047297ber and Bi1047297dobacterium lactis World J Gastroenterol2012184563ndash9
79 suchiya J Barreto R Okura R et al Single-blind ollow up study on theeffectiveness o a symbiotic preparation in irritable bowel syndromeChin J Dig Dis 20045169ndash74
80 Bittner AC Croffut RM Stranahan MC Prescript-Assist probiotic-prebi-otic treatment or irritable bowel syndrome a methodologically oriented2-week randomized placebo-controlled double-blind clinical studyClin Ter 200527755ndash61
81 Andriulli A Neri M Loguercio C et al Clinical trial on the effi cacy oa new symbiotic ormulation Flortec in patients with irritable bowelsyndrome a multicenter randomized study J Clin Gastroenterol 200842(Suppl 3) S218ndash23
82 Ford AC Quigley EM Lacy BE et al Effect o prebiotics probiotics andsynbiotics in irritable bowel syndrome and chronic idiopathic constipationsystematic review and meta-analysis Am J Gastroenterol 2014 (in press)
83 Enck P Zimmerman K Menke G et al A mixture o Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) or treatment o theirritable bowel syndrome - a randomized controlled trial with primarycare physicians Neurogastroenterol Motil 2008201103ndash9
84 Zeng J Li Y-Q Zuo X-L et al Clinical trial effect o active lactic acid bac-teria on mucosal barrier unction in patients with diarrhoea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200828994ndash1002
85 Agrawal A Houghton LA Morris J et al Clinical trial the effects o aermented milk product containing Bi1047297dobacterium lactis DN-173 010on abdominal distension and gastrointestinal transit in irritable bowelsyndrome with constipation Aliment Pharmacol Ter 201329104ndash14
86 Enck P Zimmerman K Menke G et al Randomized controlled treatmenttrial o irritable bowel syndrome with a probiotic E-coli preparation(DSM17252) compared to placebo Z Gastroenterol 200947209ndash14
87 Hong KS Kang HW Im JP et al Effect o probiotics on symptoms inKorean adults with irritable bowel syndrome Gut Liver 20093101ndash7
88 Williams EA Stimpson J Wang D et al Clinical trial a multistrainprobiotic preparation signi1047297cantly reduces symptoms o irritable bowelsyndrome in a double-blind placebo-controlled study Aliment PharmacolTer 20092997ndash103
89 Simren M Ohman L Olsson J et al Clinical trial the effects o aermented milk containing three probiotic bacteria in patients with
irritable bowel syndrome - A randomized double-blind controlled studyAliment Pharmacol Ter 201031218ndash27
90 Choi CH Jo SY Park HJ et al A randomized double-blind placebo-controlled multicenter trial o Saccharomyces boulardii in irritable bowelsyndrome effect on quality o lie J Clin Gastroenterol 201145679ndash83
91 Guglielmetti S Mora D Gschwender M et al Randomised clinical trialBi1047297dobacterium bi1047297dum MIMBb75 signi1047297cantly alleviates irritable bowelsyndrome and improves quality o lie - a double-blind placebo-controlled
study Aliment Pharmacol Ter 2011331123ndash3292 Michail S Kenche H Gut microbiota is not modi1047297ed by randomized
double-blind placebo-controlled trial o VSL3 in diarrhea-predominantirritable bowel syndrome Probiotics Antimicrob Proteins 201131ndash7
93 Sondergaard B Olsson J Ohlson K et al Effects o probiotic ermentedmilk on symptoms and intestinal 1047298ora in patients with irritable bowelsyndrome a randomized placebo-controlled trial Scand J Gastroenterol201146663ndash72
94 Cha BK Jung SM Choi CH et al Te effect o a multispecies probioticmixture on the symptoms and ecal microbiota in diarrhea-dominantirritable bowel syndrome a randomized double-blind placebo-controlledtrial J Clin Gastroenterol 201246220ndash7
95 Cui S Hu Y Multistrain probiotic preparation signi1047297cantly reduces symp-toms o irritable bowel syndrome in a double-blind placebo-controlledstudy Int J Clin Exp Med 20125238ndash44
96 Dapoigny M Piche Ducrotte P et al Effi cacy and saety pro1047297le oLCR35 complete reeze-dried culture in irritable bowel syndromea randomized double-blind study World J Gastroenterol 2012182067ndash75
97 Ducrotte P Sawant P Jayanthi V Clinical trial Lactobacillus plantarum 299v (DSM 9843) improves symptoms o irritable bowel syndrome WorldJ Gastroenterol 2012184012ndash8
98 Farup PG Jacobsen M Ligaarden SC et al Probiotics symptoms andgut microbiota what are the relations A randomized controlled trialin subjects with irritable bowel syndrome Gastroenterol Res Pract20122012214102
99 Kruis W Chrubasik S Boehm S et al A double-blind placebo-controlledtrial to study therapeutic effects o probiotic Escherichia coli Nissle 1917 insubgroups o patients with irritable bowel syndrome Int J Colorectal Dis201227467ndash74
100 Ringel-Kulka Palsson OS Maier D et al Probiotic bacteria Lactobacillusacidophilus NCFM and Bi1047297dobacterium lactis Bi-07 versus placebo orthe symptoms o bloating in patients with unctional bowel disorders
a double-blind study J Clin Gastroenterol 201145518ndash25101 Begtrup LM de Muckadell OB Kjeldsen J et al Long-term treatment
with probiotics in primary care patients with irritable bowel syndrome - arandomised double-blind placebo controlled trial Scand J Gastroenterol2013481127ndash35
102 Roberts LM McCahon D Holder R et al A randomised controlled trialo a probiotic lsquounctional oodrsquo in the management o irritable bowelsyndrome BMC Gastroenterol 20131345
103 Simren M Lindh A Samuelsson L et al Effect o yoghurt containingthree probiotic bacteria in patients with irritable bowel syndrome (IBS)- a randomized double-blind controlled trial Gastroenterology 2007132(Suppl 1) A210
104 Long ZR Yu CH Yang Y et al [Clinical observation on acupuncturecombined with microorganism pharmaceutical preparations or treatmento irritable bowel syndrome o constipation type] Zhongguo Zhen Jiu200626403ndash5
105 Drouault-Holowacz S Bieuvelet S Burckel A et al A double blind rand-omized controlled trial o a probiotic combination in 100 patients withirritable bowel syndrome Gastroenterol Clin Biol 200832147ndash52
106 Gade J Torn P Paraghurt or patients with irritable bowel syndromeScand J Prim Health Care 1989723ndash6
107 Guyonnet D Chassany O Ducrotte P et al Effect o a ermented milk con-taining Bi1047297dobacterium animalis DN-173 010 on the health-related qualityo lie and symptoms in irritable bowel syndrome in adults in primarycare a multicentre randomized double blind controlled trial AlimentPharmacol Ter 200726475ndash86
108 Kajander K Hatakka K Poussa et al A probiotic mixture alleviatessymptoms in irritable bowel syndrome patients a controlled 6-monthintervention Aliment Pharmacol Ter 200522387ndash94
109 Kajander K Myllyluoma E Rajilic-Stojanovic M et al Clinical trial multi-species probiotic supplementation alleviates the symptoms o irritablebowel syndrome and stabilizes intestinal microbiota Aliment PharmacolTer 20082748ndash57
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
110 Kim HJ Camilleri M McKinzie S et al A randomized controlled trial o aprobiotic VSL3 on gut transit and symptoms in diarrhea-predominantirritable bowel syndrome Aliment Pharmacol Ter 200317895ndash904
111 Kim HJ Vazquez Roque MI Camilleri M et al A randomized control-led trial o a probiotic combination VSL3 and placebo in irritable bowelsyndrome with bloating Neurogastroenterol Motil 200517687ndash96
112 Kim YG Moon J Lee KM et al Te effects o probiotics on symptoms oirritable bowel syndrome Korean J Gastroenterol 200647413ndash9
113 Niedzielin K Kordecki H Birkeneld B A controlled double blind rand-omized study on the effi cacy o Lactobacillus plantarum 299V in patientswith irritable bowel syndrome Eur J Gastroenterol Hepatol 2001131143
114 Niv E Nafali Hallak R et al Te effi cacy o Lactobacillus reuteri ACC55730 in the treatment o patients with irritable bowel syndrome ndasha double blind placebo-controlled randomized study Clin Nutr 200524 925ndash31
115 Nobaek S Johansson M-L Molin G et al Alteration o intestinal micro1047298o-ra is associated with reduction in abdominal bloating and pain in patientswith irritable bowel syndrome Am J Gastroenterol 2000951231ndash8
116 OrsquoMahony L McCarthy J Kelly P et al Lactobacillus and bi1047297dobacterium in irritable bowel syndrome symptom responses and relationship tocytokine pro1047297les Gastroenterology 2005128541ndash51
117 Simren M Syrous A Lindh A et al Effects o Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowelsyndrome (IBS) ndash a randomized double blind controlled trial Gastroen-
terology 2006130 (Suppl 1) A600118 Sinn DH Song JH Kim HJ et al Terapeutic effect o Lactobacillus acido-
philus -SDC 2012 2013 in patients with irritable bowel syndrome Dig DisSci 2008532714ndash8
119 Whorwell PJ Altringer L Morel J et al Effi cacy o an encapsulatedprobiotic Bi1047297dobacterium infantis 35624 in women with irritable bowelsyndrome Am J Gastroenterol 20061011581ndash90
120 Lembo A Zakko SF Ferreira NL et al Riaximin or the treatment odiarrhea-associated irritable bowel syndrome short term treatment lead-ing to long term sustained response Gastroenterology 2008134 (Suppl 1)545
121 Pimentel M Park S Mirocha J et al Te effect o a nonabsorbed oralantibiotic (riaximin) on the symptoms o the irritable bowel syndrome arandomized trial Ann Intern Med 2006145557ndash63
122 Pimentel M Lembo A Chey WD et al Riaximin therapy or patientswith irritable bowel syndrome without constipation N Engl J Med201136422ndash32
123 Sharara AI Aoun E Abdul-Baki H et al A randomized double-blindplacebo-controlled trial o riaximin in patients with abdominal bloatingand 1047298atulence Am J Gastroenterol 2006101326ndash33
124 Pimentel M Chow EJ Lin HC Normalization o lactulose breath testingcorrelates with symptom improvement in irritable bowel syndrome Adouble-blind randomized placebo-controlled study Am J Gastroenterol200398412ndash9
125 Nayak AK Karnad DR Abraham P et al Metronidazole relieves symp-toms in irritable bowel syndrome the conusion with so-called lsquochronicamebiasisrsquo Indian J Gastroenterol 199716137ndash9
126 Di Steano M ana P Mengoli C et al Colonic hypersensitivity is a majordeterminant o the effi cacy o bloating treatment in constipation-predomi-nant irritable bowel syndrome Intern Emerg Med 20116403ndash11
127 Moayyedi P Duffett S Mason S et al Te in1047298uence o antibiotics onirritable bowel syndrome a randomised controlled trial Gastroenterology2002122 (Suppl 4) A465
128 Baldi F Corinaldesi R Ferrarini F et al Clinical and unctional evaluationo octilonium bromide in the treatment o irritable bowel syndrome adouble-blind controlled trial Clin rials J 19832077ndash88
129 Castiglione F Daniele B Mazzacca G Terapeutic strategy or the irritablebowel syndrome Ital J Gastroenterol 199123 (Suppl 1) 53ndash5
130 Centonze V Imbibo BP Campanozzi F et al Oral cimetropium bromidea new antimuscarinic drug or long-term treatment o irritable bowelsyndrome Am J Gastroenterol 1988831262ndash6
131 Clave P Acalovschi M rianta1047297llidis JK et al Randomised clinical trialotilonium bromide improves requency o abdominal pain severity odistention and time to relapse in patients with irritable bowel syndromeAliment Pharmacol Ter 201134432ndash42
132 DrsquoArienzo A DrsquoAgostino L Lrsquoottilonio bromuro nel trattamento dellasiacutendrome del colon irritabile Rass Int Clin er 198060649ndash56
133 Delmont J Interet de lrsquoadjonction drsquoun antispasmodique musculotrope autraitement des constipations douloureuses des colopathies onctionnellespar le son Med Chir Dig 198110365ndash70
134 Dobrilla G Imbibo BP Piazzi L et al Long term treatment o irritablebowel syndrome with cimetropium bromide a double blind placebocontrolled clinical trial Gut 199031355ndash8
135 Fielding JF Double blind trial o trimebutine in the irritable bowel syn-drome Ir Med J 198073377ndash9
136 Ghidini O Saponati G Intrieri L Single drug treatment or irritablecolon rociverine versus trimebutine maleate Curr Ter Res Clin Exp198639541ndash8
137 Gilvarry J Kenny A Fielding JF Te non-effect o pirenzipine in dietaryresistant irritable bowel syndrome Ir J Med Sci 1989158262
138 Glende M Morselli-Labate AM Battaglia G et al Extended analysis o adouble blind placebo-controlled 15-week study with otilinium bromidein irritable bowel syndrome Eur J Gastroenterol Hepatol 2002141331ndash8
139 Levy C Charbonnier A Cachin M Pinaverium bromide and unctionalcolonic disease (double-blind study) Sem Hop Ter 197753372ndash4
140 Mitchell SA Mee AS Smith GD et al Alverine citrate ails to relievethe symptoms o irritable bowel syndrome results o a double-blindrandomized placebo-controlled trial Aliment Pharmacol Ter 2002161187ndash95
141 Moshal MG Herron M A clinical trial o trimebutine (Mebutin) in spasticcolon J Int Med Res 19797231ndash4
142 Page JG Dirnberger GM reatment o the irritable bowel syndromewith Bentyl (dicyclomine hydrochloride) J Clin Gastroenterol 19813153ndash6
143 Passaretti S Guslandi M Imbibo BP et al Effects o cimetropium bromideon gastrointestinal transit time in patients with irritable bowel syndromeAliment Pharmacol Ter 19893267ndash76
144 Piai G Mazzacca G Pri1047297nium bromide in the treatment o the irritablecolon syndrome Gastroenterology 197977500ndash2
145 Pulpeiro A Marti ML De Los Santos AR et al Propinox en sindrome deintestino irritable Prensa Med Argent 200087299ndash307
146 Schaer VE Ewe K Te treatment o irritable colon Effi cacy and toleranceo buscopan plus buscopan paracetamol and placebo in ambulatorypatients with irritable colon Fortschr Med 1990108488ndash92
147 Virat J Hueber D Colopathy pain and dicetel Prat Med 19874332ndash4148 Capanni M Surrenti E Biagini M et al Effi cacy o peppermint oil in the
treatment o irritable bowel syndrome a randomized controlled trialGazz Med Ital 2005164119ndash26
149 Cappello G Spezzaerro M Grossi L et al Peppermint oil (Mintoil) inthe treatment o irritable bowel syndrome a prospective double blindplacebo-controlled randomized trial Dig Liver Dis 200739530ndash6
150 Lech Y Olesen KM Hey H et al reatment o irritable bowel syndromewith peppermint oil A double-blind investigation with a placebo UgeskrLaeger 19881502388ndash9
151 Liu J-H Chen G-H Yeh H-Z et al Enteric-coated peppermint-oil capsulesin the treatment o irritable bowel syndrome a prospective randomizedtrial J Gastroenterol 199732765ndash8
152 Merat S Khalili S Mostajabi P et al Te effect o enteric-coated delayed-release peppermint oil on irr itable bowel syndrome Dig Dis Sci 2010551385ndash90
153 Hovdenak N Loperamide treatment o the irritable bowel syndromeScand J Gastroenterol 198713081ndash4
154 Lavo B Stenstam M Nielsen A-L Loperamide in treatment o irritablebowel syndrome - a double-blind placebo controlled study Scand JGastroenterol 198713077ndash80
155 Ford AC Quigley EM Lacy BE et al Effect o antidepressants and psycho-logical therapies including hypnotherapy in irritable bowel syndrome
systematic review and meta-analysis Am J Gastroenterol 2014 (in press)156 Bergmann M Heddergott A Schlosser Die therapie des colon irritabile
mit trimipramin (Herphonal) - Eine kontrollierte studie Z Klin Med1991461621ndash8
157 Boerner D Eberhardt R Metz K et al Wirksamkeit und vertraglichkeiteines antidepressivuns beim colon irritabile Terapiewoche 198838 201ndash8
158 Heener JD Wilder RM Wilson ID Irritable colon and depressionPsychosomatics 197819540ndash7
159 Kuiken SD ytgat GNJ Boeckxstaens GEE Te selective serotoninreuptake inhibitor 1047298uoxetine does not change rectal sensitivity andsymptoms in patients with irritable bowel syndrome a double-blindrandomized placebo-controlled study Clin Gastroenterol Hepatol20031219ndash28
160 Myren J Groth H Larssen SE et al Te effect o trimipramine in patientswith the irritable bowel syndrome a double-blind study Scand J Gastro-enterol 198217871ndash5
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
The American Journal of GASTROENTEROLOGY VOLUME 109 | SUPPLEMENT 1 | AUGUST 2014 wwwamjgastrocom
24 Ford et al
161 abas G Beaves M Wang J et al Paroxetine to treat irritable bowelsyndrome not responding to high 1047297ber diet a double-blind placebo-controlled trial Am J Gastroenterol 200499914ndash20
162 ack J Broekaert D Fischler B et al A controlled crossover study o theselective serotonin reuptake inhibitor citalopram in irritable bowel syn-drome Gut 2006551095ndash103
163 alley NJ Kellow JE Boyce P et al Antidepressant therapy (imipramineand citalopram) or irritable bowel syndrome a double-blind rand-omized placebo-controlled trial Dig Dis Sci 200853108ndash15
164 Vahedi H Merat S Rashidioon A et al Te effect o 1047298uoxetine in patientswith pain and constipation-predominant irritable bowel syndrome a double-blind randomized-controlled study Aliment Pharmacol Ter 200522381ndash5
165 Vahedi H Merat S Momtahen S et al Clinical trial the effect o amitripty-line in patients with diarrhea-predominant irritable bowel syndromeAliment Pharmacol Ter 200827678ndash84
166 Vij JC Jiloha RC Kumar N et al Effect o antidepressant drug (doxepin)on irritable bowel syndrome patients Indian J Psychiatry 199133243ndash6
167 Drossman DA oner BB Whitehead WE et al Cognitive-behavioraltherapy versus education and desipramine versus placebo or moderate tosevere unctional bowel disorders Gastroenterology 200312519ndash31
168 Abdul-Baki H El Hajj ElZahabi L et al A randomized controlled trialo imipramine in patients with irritable bowel syndrome World J Gastro-enterol 2009153636ndash42
169 Ghadir MR Habibinejad H Heidari A et al Doxepin is more effective
than nortriptyline and placebo or the treatment o diarrhea-predominantirritable bowel syndrome a randomized triple-blind placebo-controlledtrial ehran Univ Med J 201169352ndash8
170 Ladabaum U Sharabidze A Levin R et al Citalopram is not effectivetherapy or nondepressed patients with irritable bowel syndrome ClinGastroenterol Hepatol 2010842ndash8
171 Masand PS Pae C-U Krulewicz S et al A double-blind randomizedplacebo-controlled trial o paroxetine controlled-release in irritable bowelsyndrome Psychosomatics 20095078ndash86
172 Blanchard EB Schwarz SP Suls JM et al wo controlled evaluations omulticomponent psychological treatment o irr itable bowel syndromeBehav Res Ter 199230175ndash89
173 Blanchard EB Greene B Scharff L et al Relaxation training as a treatmentor irritable bowel syndrome Bioeedback Sel Regul 199318125ndash31
174 Boyce PM alley NJ Balaam B et al A randomized controlled trial ocognitive behavior therapy relaxation training and routine clinical careor the irritable bowel syndrome Am J Gastroenterol 2003982209ndash18
175 Creed F Fernandes L Guthrie E et al Te cost-effectiveness o psycho-therapy and paroxetine or severe irritable bowel syndrome Gastro-enterology 2003124303ndash17
176 Galovski E Blanchard EB Te treatment o irritable bowel syndromewith hypnotherapy Appl Psychophysiol Bioeedback 199823219ndash32
177 Greene B Blanchard EB Cognitive therapy or irritable bowel syndromeJ Consult Clin Psychol 199462576ndash82
178 Guthrie E Creed F Dawson D et al A controlled trial o psycho-logical treatment or the irritable bowel syndrome Gastroenterology1991100450ndash7
179 Heitkemper M Jarrett ME Levy RL et al Sel-management or womenwith irritable bowel syndrome Clin Gastroenterol Hepatol 20042585ndash96
180 Keeer L Blanchard EB Te effects o relaxation response meditation onthe symptoms o irritable bowel syndrome results o a controlled treat-ment study Behav Res Ter 200139801ndash11
181 Kennedy Jones R Darnley S et al Cognitive behaviour therapy in addi-
tion to antispasmodic treatment or irritable bowel syndrome in primarycare randomised controlled trial BMJ 2005331435ndash7
182 Lynch PM Zamble E A controlled behavioral treatment study o irritablebowel syndrome Behav Ter 198920509ndash23
183 Neff DF Blanchard EB A multi-component treatment or irritable bowelsyndrome Behav Ter 19871870ndash83
184 Payne A Blanchard EB A controlled comparison o cognitive therapyand sel-help support groups in the treatment o irr itable bowel syndromeJ Consult Clin Psychol 199563779ndash86
185 Sanders KA Blanchard EB Sykes MA Preliminary study o a sel-admin-istered treatment or irritable bowel syndrome comparison to a wait listcontrol group Appl Psychophysiol Bioeedback 200732111ndash9
186 Shaw G Srivastava ED Sadlier M et al Stress management or irritablebowel syndrome a controlled trial Digestion 19915036ndash42
187 Simren M Ringstrom G Bjornsson ES et al reatment with hypnotherapyreduces the sensory and motor component o the gastrocolonic responsein irritable bowel syndrome Psychosom Med 200466233ndash8
188 kachuk GA Graff LA Martin GL et al Randomized controlled trialo cognitive-behavioral group therapy or irritable bowel syndrome in amedical setting J Clin Psychol Med Settings 20031057ndash69
189 van der Veek PPJ van Rood YR Masclee AAM Clinical trial short- andlong-term bene1047297t o relaxation training or irritable bowel syndromeAliment Pharmacol Ter 200726943ndash52
190 Vollmer A Blanchard EB Controlled comparison o individual versusgroup cognitive therapy or irritable bowel syndrome Behav Ter19982919ndash33
191 Craske MG Wolitzky-aylor KB Labus J et al A cognitive-behavioraltreatment or irritable bowel syndrome using interoceptive exposure to visceral sensations Behav Res Ter 201149413ndash21
192 Gaylord SA Palsson OS Garland EL et al Mindulness training reducesthe severity o irr itable bowel syndrome in women results o a rand-omized controlled trial Am J Gastroenterol 20111061678ndash88
193 Hunt MG Moshier S Milonova M Brie cognitive-behavioral internettherapy or irritable bowel syndrome Behav Res Ter 200947797ndash802
194 Jarrett ME Cain KC Burr RL et al Comprehensive sel-managementor irritable bowel syndrome randomized trial o in-person vs combinedin-person and telephone sessions Am J Gastroenterol 20091043004ndash14
195 Lackner JM Jaccard J Krasner SS et al Sel-administered cognitivebehavior therapy or moderate to severe irr itable bowel syndromeclinical effi cacy tolerability easibility Clin Gastroenterol Hepatol 20086 899ndash906
196 Lindors P Unge P Arvidsson P et al Effects o gut-directed hypnotherapyon IBS in different clinical settings - results rom two randomizedcontrolled trials Am J Gastroenterol 2012107276ndash85
197 Ljotsson B Falk L Wibron Vesterlund A et al Internet-delivered exposureand mindulness based therapy or irritable bowel syndrome - a rand-omized controlled trial Behav Res Ter 201048531ndash9
198 Moser G ragner S Elwira Gajowniczek E et al Long-term successo GU-directed group hypnosis or patients with reractory irritablebowel syndrome a randomized controlled trial Am J Gastroenterol2013108602ndash9
199 Moss-Morris R McAlpine L Didsbury LP et al A randomized control-led trial o a cognitive behavioural therapy-based sel-managementintervention or irritable bowel syndrome in primary care Psychol Med20104085ndash94
200 Shinozaki M Kanazawa M Kano M et al Effect o autogenic training ongeneral improvement in patients with irritable bowel syndrome a rand-omized controlled trial Appl Psychophysiol Bioeedback 201035189ndash98
201 Gershon MD Review article serotonin receptors and transporters -- rolesin normal and abnormal gastrointestinal motility Aliment PharmacolTer 200420 (Suppl 7) 3ndash14
202 Spiller R Serotonergic modulating drugs or unctional gastrointestinaldiseases Br J Clin Pharmacol 20025411ndash20
203 Goldberg PA Kamm MA Setti-Carraro P et al Modi1047297cation o visceralsensitivity and pain in irritable bowel syndrome by 5-H3 antagonism(ondansetron) Digestion 199657478ndash83
204 Houghton LA Foster JM Whorwell PJ Alosetron a 5-H3 receptorantagonist delays colonic transit in patients with irritable bowel syndromeand healthy volunteers Aliment Pharmacol Ter 200014775ndash82
205 Miller DP Alredson Cook SF et al Incidence o colonic ischemiahospitalized complications o constipation and bowel surgery in relationto use o alosetron hydrochloride Am J Gastroenterol 2003981117ndash22
206 Grider JR Foxx-Orenstein AE Jin JG 5-Hydroxytryptamine4 receptoragonists initiate the peristaltic re1047298ex in human rat and guinea pig
intestine Gastroenterology 1998115370ndash80207 Prather CM Camilleri M Zinsmeister AR et al egaserod accelerates
orocecal transit in patients with constipation-predominant irritable bowelsyndrome Gastroenterology 2000118463ndash8
208 Bardhan KD Bodemar G Geldo H et al A double-blind randomizedplacebo-controlled dose-ranging study to evaluate the effi cacy o alosetronin the treatment o irritable bowel syndrome Aliment Pharmacol Ter20001423ndash34
209 Bradette M Moennikes H Carter F et al Cilansetron in irritable bowelsyndrome with diarrhea predominance (IBS-D) effi cacy and saety ina 6 month global study Gastroenterology 2004126 (Suppl 2) A42
210 Camilleri M Mayer EA Drossman DA et al Improvement in pain andbowel unction in emale irritable bowel patients with alosetron a 5-H
3
receptor antagonist Aliment Pharmacol Ter 1999131149ndash59211 Camilleri M Northcutt AR Kong S et al Effi cacy and saety o alosetron
in women with irritable bowel syndrome a randomised placebo-controlled trial Lancet 20003551035ndash40
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
copy 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
SACG Monograph on IBS and CIC
212 Camilleri M Chey WY Mayer EA et al A randomized controlled clinical trialo the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome Arch Intern Med 20011611733ndash40
213 Chang L Ameen VZ Dukes GE et al A dose-ranging phase II study othe effi cacy and saety o alosetron in men with diarrhea-predominantIBS Am J Gastroenterol 2005100115ndash23
214 Chey WD Chey WY Heath A et al Long-term saety and effi cacy oalosetron in women with severe diarrhea-predominant irritable bowelsyndrome Am J Gastroenterol 2004992195ndash203
215 Francisconi CF Drossman DA Mayer EA et al Interruption o daily acti- vities in cilansetron-treated patients with irritable bowel syndrome withdiarrhea-predominance (IBS-D) results rom a 16-week placebo-control-led rerandomization trial Gastroenterology 2006130 (Suppl 2) A600
216 Krause R Ameen V Gordon SH et al A randomized double-blindplacebo-controlled study to assess effi cacy and saety o 05 mg and 1 mgalosetron in women with severe diarrhea-predominant IBS Am J Gastro-enterol 20071021709ndash19
217 Lembo Wright RA Lotronex Investigator eam et al Alosetron controlsbowel urgency and provides global symptom improvement in womenwith diarrhea-predominant irritable bowel syndrome Am J Gastroenterol2001962662ndash70
218 Matsueda K Harasawa S Hongo M et al A phase II trial o the novel sero-tonin type 3 receptor antagonist ramosetron in Japanese male and emalepatients with diarrhea-predominant irritable bowel syndrome Digestion
200877225ndash35219 Matsueda K Harasawa S Hongo M et al A randomized double-blind
placebo-controlled clinical trial o the effectiveness o the novel serotonintype 3 receptor antagonist ramosetron in both male and emale Japanesepatients with diarrhea-predominant irritable bowel syndrome Scand JGastroenterol 2008431202ndash11
220 Miner P Stanton D Carter F et al Cilansetron in irritable bowel syndromewith diarrhea predominance (IBS-D) effi cacy and saety in a 3 month USstudy Am J Gastroenterol 200499 (Suppl) S277
221 httpwwwdagovdownloadsDrugsDrugSaetyPostmarketDrugSaety InormationorPatientsandProvidersUCM227960pd (accessed June 10th2014)
222 Camilleri M McKinzie S Fox J et al Effect o renzapride on transit inconstipation-predominant irritable bowel syndrome Clin GastroenterolHepatol 20042895ndash904
223 Farup PG Hovdenak N Wetterhus S et al Te symptomatic effect ocisapride in patients with irritable bowel syndrome and constipationScand J Gastroenterol 199833128ndash31
224 George AM Meyers NL Hickling RI Clinical trial renzapride therapyor constipation-predominant irritable bowel syndrome - multicentrerandomized placebo-controlled double-blind study in primary healthcaresetting Aliment Pharmacol Ter 200827830ndash7
225 Schutze K Brandstatter G Dragosics B et al Double-blind study othe effect o cisapride on constipation and abdominal discomort ascomponents o the irritable bowel syndrome Aliment Pharmacol Ter199711387ndash94
226 Spiller RC Meyers NL Hickling RI Identi1047297cation o patients with non-D non-C irritable bowel syndrome and treatment with renzapride anexploratory multicenter randomized double-blind placebo-controlledclinical trial Dig Dis Sci 2008533191ndash200
227 Van Outryve M Milo R oussaint J et al ldquoProkineticrdquo treatment o consti-pation-predominant irritable bowel syndrome a placebo-controlled studyo cisapride J Clin Gastroenterol 19911349ndash57
228 Ziegenhagen DJ Kruis W Cisapride treatment o constipation-predomi-nant irritable bowel syndrome is not superior to placebo J GastroenterolHepatol 200419744ndash9
229 Lembo AJ Cremonini F Meyers N et al Clinical trial renzapride treat-ment o women with irritable bowel syndrome and constipation - adouble-blind randomized placebo-controlled study Aliment PharmacolTer 201031979ndash90
230 Mansour NM Ghaith O El-Halabi M et al A prospective randomizedtrial o mosapride vs placebo in constipation-predominant irritable bowelsyndrome Am J Gastroenterol 2012107792ndash3
231 Forte LR Guanylin regulatory peptides structures biological activitiesmediated by cyclic GMP and pathobiology Regulat Pept 19998125ndash39
232 Chey WD Lembo AJ Lavins BJ et al Linaclotide or irritable bowel syndromewith constipation a 26-week randomized double-blind placebo-controlledtrial to evaluate effi cacy and saety Am J Gastroenterol 20121071702ndash12
233 Johnston JM Kurtz CB MacDougall JE et al Linaclotide improvesabdominal pain and bowel habits in a phase IIb study o patients with
irritable bowel syndrome and constipation Gastroenterology 20101391877ndash86
234 Rao S Lembo AJ Shiff SJ et al 12-week randomized controlled trialwith a 4-week randomized withdrawal period to evaluate the effi cacyand saety o linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol 20121071714ndash24
235 Drossman DA Chey WD Johanson JF et al Clinical trial lubiprostone inpatients with constipation-associated irritable bowel syndrome - resultso two randomized placebo-controlled studies Aliment Pharmacol Ter200929329ndash41
236 Fukudo S Hongo M Kaneko H et al Effi cacy o lubiprostone in patientswith constipation with or without irritable bowel syndrome in Japanrandomized placebo-controlled and dose-1047297nding study Gastroenterology2010130 (Suppl 1) 1435ndash6
237 Johanson JF Drossman DA Panas R et al Clinical trial phase 2 studyo lubiprostone or irritable bowel syndrome with constipation AlimentPharmacol Ter 200827685ndash96
238 Khoshoo V Armstead C Landry L Effect o a laxative with and withouttegaserod in adolescents with constipation predominant irritable bowelsyndrome Aliment Pharmacol Ter 200623191ndash6
239 Awad RA Camacho S A randomized double-blind placebo-controlledtrial o polyethylene glycol effects on asting and postprandial rectal sensi-tivity and symptoms in hypersensitive constipation-predominant irritablebowel syndrome Colorectal Dis 2010121131ndash8
240 Chapman RW Stanghellini V Geraint M et al Randomized clinicaltrial macrogolPEG 3350 plus electrolytes or treatment o patients withconstipation associated with irritable bowel syndrome Am J Gastroenterol20131081508ndash15
241 Ashra W Park F Lo J et al Effects o psyllium therapy on stool character-istics colon transit and anorectal unction in chronic idiopathic constipa-tion Aliment Pharmacol Ter 19959639ndash47
242 Badiali D Corazziari E Habib FI et al Effect o wheat bran in treatment ochronic non-organic constipation A double-blind controlled trial Dig DisSci 199540349ndash56
243 Fenn GC Wilkinson PD Lee CE et al A general practice study o the effi -cacy o Regulan in unctional constipation Br J Gen Pract 198640192ndash7
244 Hongisto S-M Paajanen L Saxelin M et al A combination o 1047297bre-richrye bread and yoghurt containing Lactobacillus GG improves bowel unc-tion in women with sel-reported constipation Eur J Clin Nutr 200660 319ndash24
245 Lopez Roman J Martinez Gonzalvez AB Luque A et al Eecto de laingesta de un preparado lacteo con 1047297bra dietetica sobre el estrenimientocronic primario idiopatico] Nutr Hosp 20082312ndash9
246 Nunes FP Nunes CP Levis E et al A double-blind trial o a celandinaloevera and psyllium laxative preparation in adult patients with constipa-tion Rev Bras Med 200562352ndash7
247 Corazziari E Badiali D Habib FI et al Small volume isosmotic polyethyl-ene glycol electrolyte balanced solution (PMF-100) in treatment o chronicnonorganic constipation Dig Dis Sci 1996411636ndash42
248 Corazziari E Badiali D Bazzocchi G et al Long term effi cacy saety andtolerability o low daily doses o isosmotic polyethylene glycol electrolytebalanced solution (PMF-100) in the treatment o unctional chronic con-stipation Gut 200046522ndash6
249 DiPalma JA DeRidder PH Orlando RC et al A randomized placebo-controlled multicenter study o the saety and effi cacy o a new polyethyl-ene glycol laxative Am J Gastroenterol 200095446ndash50
250 DiPalma JA Cleveland MV McGowan J et al A randomized multicenter
placebo-controlled trial o polyethylene glycol laxative or chronic treat-ment o chronic constipation Am J Gastroenterol 20071021436ndash41
251 Baldonedo YC Lugo E Uzcategui AA et al Evaluation and use o polyeth-ylene glycol in constipated patients] G E N 199145294ndash7
252 Wesselius-De Casparis A Braadbaart S Bergh-Bohlken GE et al reat-ment o chronic constipation with lactulose syrup results o a double-blind study Gut 1968984ndash6
253 Sander JF Lactulose syrup assessed in a double-blind study in elderlyconstipated patients J Am Geriatr Soc 197826236ndash9
254 Kamm MA Mueller-Lissner S Wald A et al Oral bisacodyl is effective andwell-tolerated in patients with chronic constipation Clin GastroenterolHepatol 20119577ndash83
255 Mueller-Lissner S Kamm MA Wald A et al Multicenter 4-week double-blind randomized placebo-controlled trial o sodium picosulate inpatients with chronic constipation Am J Gastroenterol 2010105897ndash903
256 Kim DY Camilleri M Serotonin a mediator o the brain-gut connectionAm J Gastroenterol 2000952698ndash709
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46
257 Camilleri M Kerstens R Rykx A et al A placebo-controlled trial o pruca-lopride or severe chronic constipation N Engl J Med 20083582344ndash54
258 Coremans G Kerstens R De Pauw M et al Prucalopride is effective inpatients with severe chronic constipation in whom laxatives ail to provideadequate relie Digestion 20036782ndash9
259 Emmanuel AV Roy AJ Nicholls J et al Prucalopride a systemic enterokineticor the treatment o constipation Aliment Pharmacol Ter 2002161347ndash56
260 Goldberg M Li Y-P Johanson JF et al Clinical trial the effi cacy and tolerabilityo velusetrag a selective 5-H
4 agonist with high intrinsic activity in chronic
idiopathic constipation ndash a 4-week randomized double-blind placebo-controlled dosendashresponse study Aliment Pharmacol Ter 2010321102ndash12
261 Miner PB Nichols Silvers DR et al Te effi cacy and saety o prucalo-pride in patients with chronic constipation Gastroenterology 1999116(Suppl) A1043
262 Muller-Lissner S Rykx A Kerstens R et al A double-blind placebo-controlled study o prucalopride in elderly patients with chronicconstipation Neurogastroenterol Motil 201022991ndash8
263 Quigley EMM Vandeplassche L Kerstens R et al Clinical trial theeffi cacy impact on quality o lie and saety and tolerability o prucalo-pride in severe chronic constipation - a 12-week randomized double-blind placebo-controlled study Aliment Pharmacol Ter 200929315ndash28
264 ack J Van Outryve M Beyens M et al Prucalopride (Resolor) in thetreatment o severe chronic constipation in patients dissatis1047297ed withlaxatives Gut 200958357ndash65
265 Ke M Zou D Yuan Y et al Prucalopride in the treatment o chronicconstipation in patients rom the Asia-Paci1047297c region a randomizeddouble-blind placebo-controlled study Neurogastroenterol Motil201224999ndashe541
266 Lembo AJ Kurtz CB MacDougall JE et al Effi cacy o l inaclotide orpatients with chronic constipation Gastroenterology 2010138886ndash95
267 Lembo AJ Schneier HA Shiff SJ et al wo randomized trials o linaclotideor chronic constipation N Engl J Med 2011365527ndash36
268 Barish CF Drossman D Johanson JF et al Effi cacy and saety o lubiprostonein patients with chronic constipation Dig Dis Sci 2010551090ndash7
269 Johanson JF Ueno R Lubiprostone a local ly acting chloride channelactivator in adult patients with chronic constipation a double-blindplacebo-controlled dose-ranging study to evaluate effi cacy and saetyAliment Pharmacol Ter 2007251351ndash61
270 Johanson JF Morton D Geene J et al Multicenter 4-week double-blindrandomized placebo-controlled trial o lubiprostone a locally-actingtype-2 chloride channel activator in patients with chronic constipationAm J Gastroenterol 2008103170ndash7
271 Rao S Meduri K uteja A et al Effects o lubiprostone on gastrointestinalsymptoms bowel unction and bowel satisaction in patients with metha-nogenic 1047298ora and chronic constipation Am J Gastroenterol 2012107(Suppl 1s) S712ndash3
272 Bharucha AE Pelvic 1047298oor anatomy and unction NeurogastroenterolMotil 200618507ndash19
273 Faubion SS Schuster L Bharucha AE Recognition and management ononrelaxing pelvic 1047298oor dysunction Mayo Clin Proc 201287187ndash93
274 Chiarioni G Whitehead WE Pezza V et al Bioeedback is superior tolaxatives or normal transit constipation due to pelvic 1047298oor dyssynergiaGastroenterology 2006130657ndash64
275 Heymen S Scarlett Y Jones K et al Randomized controlled trial showsbioeedback to be superior to alternative treatments or patients withpelvic 1047298oor dyssynergia-type constipation Dis Colon Rectum 200750428ndash41
276 Rao SS Seaton K Miller M et al Randomized controlled trial o bioeed-back sham eedback and standard therapy or dyssynergic deecationClin Gastroenterol Hepatol 20075331ndash8
277 Hart SL Lee JW Berian J et al A randomized controlled trial o anorectalbioeedback or constipation Int J Colorectal Dis 201227459ndash66
278 Simon MA Bueno AM Behavioural treatment o the dyssynergic deeca-tion in chronically constipated elderly patients a randomized controlledtrial Appl Psychophysiol Bioeedback 200934273ndash7
279 Glia A Gylin M Gullberg K et al Bioeedback retraining in patientswith unctional constipation and paradoxical puborectalis contractioncomparison o anal manometry and sphincter electromyography or eed-back Dis Colon Rectum 199740889ndash95
280 Koutsomanis D Lennard-Jones JE Roy AJ et al Controlled randomisedtrial o visual bioeedback versus muscle training without a visual displayor intractable constipation Gut 19953795ndash9
281 Heymen S Wexner SD Vickers D et al Prospective randomized trialcomparing our bioeedback techniques or patients with constipation
Dis Colon Rectum 1999421388ndash93282 Pourmomeny AA Emami MH Amooshahi M et al Comparing the
effi cacy o bioeedback and balloon-assisted training in the treatment odyssynergic deecation Can J Gastroenterol 20112589ndash92
283 Chey WD Camilleri M Chang L et al A randomized placebo-controlledphase IIb trial o a3309 a bile acid transporter inhibitor or chronicidiopathic constipation Am J Gastroenterol 20111061803ndash12
284 Simren M Bajor A Gillberg PG et al Randomised clinical trial the ilealbile acid transporter inhibitor A3309 vs placebo in patients with chronicidiopathic constipation--a double-blind study Aliment Pharmacol Ter20113441ndash50
285 Wong BS Camilleri M McKinzie S et al Effects o A3309 an ileal bileacid transporter inhibitor on colonic transit and symptoms in emaleswith unctional constipation Am J Gastroenterol 20111062154ndash64
286 Koebnick C Wagner I Leitzmann P et al Probiotic beverage containingLactobacillus casei Shirota improves gastrointestinal symptoms in patientswith chronic constipation Can J Gastroenterol 200317655ndash9
287 Sakai Makino H Ishikawa E et al Fermented milk containing Lacto-bacillus casei strain Shirota reduces incidence o hard or lumpy stools inhealthy population Int J Food Sci Nutr 201162423ndash30
288 Yang YX He M Hu G et al Effect o a ermented milk containingBi1047297dobacterium lactis DN-173010 on Chinese constipated womenWorld J Gastroenterol 2008146237ndash43
289 Bracco A Jonsson B Ricci J-F et al Economic evaluation o tegaserod vs placebo in the treatment o patients with irritable bowel syndrome ananalysis o the ENOR study Value in Health 200710238ndash46