Ellen Frank, Ph.D. Ellen Frank, Ph.D. Jessica Levenson, M.S. Jessica Levenson, M.S. Yu Cheng, Ph.D. Yu Cheng, Ph.D. University of Pittsburgh School of University of Pittsburgh School of Medicine Medicine Pittsburgh, PA USA Pittsburgh, PA USA
Jan 17, 2018
Ellen Frank, Ph.D.Ellen Frank, Ph.D.Jessica Levenson, M.S.Jessica Levenson, M.S.
Yu Cheng, Ph.D.Yu Cheng, Ph.D.University of Pittsburgh School of MedicineUniversity of Pittsburgh School of Medicine
Pittsburgh, PA USAPittsburgh, PA USA
DisclosuresDisclosuresEllen Frank, Ph.DEllen Frank, Ph.D..
• Advisory Board – Servier InternationalAdvisory Board – Servier International• Royalties – Guilford Press; American Royalties – Guilford Press; American
Psychological AssociationPsychological Association
Advantages and Disadvantages of Advantages and Disadvantages of Pharmacotherapy ComparatorsPharmacotherapy Comparators
• Answers an important question:Answers an important question:• “ “How does IPT compare to the most commonly How does IPT compare to the most commonly
used treatment for depression?”used treatment for depression?”• Ecological validity? – tension between ‘real Ecological validity? – tension between ‘real
world’ and ‘equating’ treatments for time world’ and ‘equating’ treatments for time and attentionand attention• Represents a choice with which clinicians are Represents a choice with which clinicians are
often facedoften faced• Rarely provides pharmacotherapy as it is likely Rarely provides pharmacotherapy as it is likely
to be done in actual practice settingsto be done in actual practice settings
Issues to Consider - IIssues to Consider - I• What drug(s)?What drug(s)?• At what dose(s)?At what dose(s)?• Who provides the pharmacotherapy?Who provides the pharmacotherapy?• How often are pharmacotherapy visits How often are pharmacotherapy visits
scheduled?scheduled?• How long do pharmacotherapy visits last?How long do pharmacotherapy visits last?
Issues to Consider - IIIssues to Consider - II• Do pharmacotherapists follow a manual?Do pharmacotherapists follow a manual?• Are pharmacotherapy sessions monitored Are pharmacotherapy sessions monitored
via audio or video tape?via audio or video tape?• Are other interventions allowed?Are other interventions allowed?• Are patient preferences assessed?Are patient preferences assessed?
Representative Depression Representative Depression Studies with Pharmacotherapy Studies with Pharmacotherapy ComparatorsComparators• Klerman et al, 1974 (maintenance of acute Klerman et al, 1974 (maintenance of acute
response)response)• Weissman et al, 1979 (acute depression)Weissman et al, 1979 (acute depression)• Elkin et al, 1988 (acute depression)Elkin et al, 1988 (acute depression)• Frank et al, 1990 (maintenance of remission)Frank et al, 1990 (maintenance of remission)• Markowitz et al, 2005 (dysthymia)Markowitz et al, 2005 (dysthymia)• Blom et al, 2007 (acute depression)Blom et al, 2007 (acute depression)• Frank et al, 2011 (acute depression)Frank et al, 2011 (acute depression)
Klerman et al , 1974 - IKlerman et al , 1974 - I• Drug – amitriptyline Drug – amitriptyline • Dose – 100-200mgDose – 100-200mg• Pharmacotherapists – psychiatrists?Pharmacotherapists – psychiatrists?• Frequency of visits – 1/monthFrequency of visits – 1/month• Length of visits- 15 minutes (including Length of visits- 15 minutes (including
completion of rating scales)completion of rating scales)
Klerman et al, 1974 - IIKlerman et al, 1974 - II• Pharmacotherapy manual – apparently notPharmacotherapy manual – apparently not• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – unclearaudio or video tape – unclear• Other interventions allowed – not Other interventions allowed – not
discusseddiscussed• Patient preferences assessed – not Patient preferences assessed – not
discusseddiscussed
Weissman et al , 1979 - IWeissman et al , 1979 - I• Drug – amitriptyline Drug – amitriptyline • Dose – 100-200mgDose – 100-200mg• Pharmacotherapists – psychiatrists?Pharmacotherapists – psychiatrists?• Frequency of visits – not describedFrequency of visits – not described• Length of visits – not describedLength of visits – not described
Weissman et al, 1979 - IIWeissman et al, 1979 - II• Pharmacotherapy manual – apparently notPharmacotherapy manual – apparently not• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – unclearaudio or video tape – unclear• Other interventions allowed – not Other interventions allowed – not
discusseddiscussed• Patient preferences assessed – not Patient preferences assessed – not
discusseddiscussed
Elkin et al , 1988 - IElkin et al , 1988 - I• Drug – imipramine Drug – imipramine • Dose – flexible; mean=185mgDose – flexible; mean=185mg• Pharmacotherapists – psychiatristsPharmacotherapists – psychiatrists• Frequency of visits – 1/weekFrequency of visits – 1/week• Length of visits- 1Length of visits- 1stst visit, 45-60min; visit, 45-60min;
subsequent visits, 20-30minsubsequent visits, 20-30min
Elkin et al, 1974 - IIElkin et al, 1974 - II• Pharmacotherapy manual – yes (Fawcett, Pharmacotherapy manual – yes (Fawcett,
et al)et al)• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – yesaudio or video tape – yes• Other interventions allowed – noOther interventions allowed – no• Patient preferences assessed – not Patient preferences assessed – not
discusseddiscussed
Frank et al , 1990 - IFrank et al , 1990 - I• Drug – imipramine Drug – imipramine • Dose – flexible; mean = 216mgDose – flexible; mean = 216mg• Pharmacotherapists – non-MD mental Pharmacotherapists – non-MD mental
health clinicianshealth clinicians• Frequency of visits – 1/monthFrequency of visits – 1/month• Length of visits- ~20 minutesLength of visits- ~20 minutes
Frank et al, 1990 - IIFrank et al, 1990 - II• Pharmacotherapy manual – yes (adapted Pharmacotherapy manual – yes (adapted
from Fawcett, et al.)from Fawcett, et al.)• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – yesaudio or video tape – yes• Other interventions allowed – noOther interventions allowed – no• Patient preferences assessed – not Patient preferences assessed – not
discusseddiscussed
Markowitz et al , 2005 - IMarkowitz et al , 2005 - I• Drug – sertraline Drug – sertraline • Dose – 112mg Dose – 112mg • Pharmacotherapists – psychiatrists?Pharmacotherapists – psychiatrists?• Frequency of visits – weekly, then Frequency of visits – weekly, then
biweekly (total of 10)biweekly (total of 10)• Length of visits - initial visit 45-60min; Length of visits - initial visit 45-60min;
subsequent visits 20-30minsubsequent visits 20-30min
Markowitz et al, 2005 - IIMarkowitz et al, 2005 - II• Pharmacotherapy manual – yes (Fawcett Pharmacotherapy manual – yes (Fawcett
et al)et al)• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – yesaudio or video tape – yes• Other interventions allowed – not Other interventions allowed – not
discusseddiscussed• Patient preferences assessed – not Patient preferences assessed – not
discusseddiscussed
Blom et al , 2007 - IBlom et al , 2007 - I• Drug – nefazodone Drug – nefazodone • Dose – mean=490mgDose – mean=490mg• Pharmacotherapists – psychiatrists or Pharmacotherapists – psychiatrists or
psychiatric residentspsychiatric residents• Frequency of visits – weekly?Frequency of visits – weekly?• Length of visits- initial visit 30min; Length of visits- initial visit 30min;
subsequent visits 15minsubsequent visits 15min
Blom et al, 2007 - IIBlom et al, 2007 - II• Pharmacotherapy manual – yes (adapted Pharmacotherapy manual – yes (adapted
from Fawcett et al)from Fawcett et al)• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – yesaudio or video tape – yes• Other interventions allowed – oxazepamOther interventions allowed – oxazepam• Patient preferences assessed – not Patient preferences assessed – not
discusseddiscussed
Frank et al , 2011 - IFrank et al , 2011 - I• Drug – escitalopram Drug – escitalopram • Dose – mean=490mgDose – mean=490mg• Pharmacotherapists – psychiatrists at Pharmacotherapists – psychiatrists at
Pisa; non-MD MH professionals at Pisa; non-MD MH professionals at PittsburghPittsburgh
• Frequency of visits – weeklyFrequency of visits – weekly• Length of visits- 20-30minLength of visits- 20-30min
Frank et al, 2011 - IIFrank et al, 2011 - II• Pharmacotherapy manual – yes (adapted Pharmacotherapy manual – yes (adapted
from Fawcett et al)from Fawcett et al)• Pharmacotherapy sessions monitored via Pharmacotherapy sessions monitored via
audio or video tape – yesaudio or video tape – yes• Other interventions allowed – low-dose Other interventions allowed – low-dose
benzodiazepines for sleepbenzodiazepines for sleep• Patient preferences assessed – yesPatient preferences assessed – yes
IPT v. Pharmacotherapy ESs and NNTsIPT v. Pharmacotherapy ESs and NNTsAuthor Populatio
nDesign Duration Depression
MeasureEffect Size1
Klerman et al., 1974
150 women with ‘neurotic’ depression
6 ‘maintenance’ tx conditions: drug, PBO or no pill crossed with ‘low contact’ v.‘high contact’ (IPT precursor)
8 months Cumulative chance of relapse
ES= -.12NNT= -25
Weissman et al., 1979
Acute depression
IPT (n=17) v. IPT+AMI (n=23) v. NST (n=21) v. AMI (n=20)
16 weeks Time to sx failure (Raskin > 9)
ES =.33NNT=7.1
Elkin et al., 1988
Acute depression
IPT (n=61) v. CBT (n=69) v. IMI-CM (n=57 ) v. PBO-CM (n=62)
16 weeks BDI, HSCL-90HRSD-17, GASRecovery: yes/noRecovery: yes/no by severity
ES=.02NNT=100
1ES calculated comparing IPT alone to pharmacotherapy alone based on arcsin transformations of two proportions, NNT the inverse of the difference in two proportions
IPT v. Pharmacotherapy ESs and NNTsIPT v. Pharmacotherapy ESs and NNTsAuthor Population Design Duration Depression
MeasureEffect Size1
Frank et al., 1990
Recurrent depression
5 maintenance tx conditions: IPT-M (n=26) , IPT-M +PBO (n=26),IPT-M+IMI (n=25), CM+PBO (n=23), CM+IMI (n=28)
3 years Time to recurrence
ES= -.77NNT = -2.7
Markowitz et al., 2005
Dysthymia IPT (n=23) v. BSP (n=26) v. SERT (n=24) v. IPT+SERT (n=21)
16 weeks HRSD-24, BDI,CDRS,IIP, SAS
ES = -.47NNT= -4.3
Blom et al., 2007
Acute depression
IPT (n=50) v. IPT+PBO (n=47)NEF (n=47) v. IPT+NEF (n=49 )
16 weeks HRSD-17*, MADRS, CGI
ES2=.09
1ES calculated comparing IPT alone to pharmacotherapy alone based on arcsin transformations of two proportions, NNT the inverse of the difference in two proportions 2ES calculated comparing IPT alone to pharmacotherapy alone based on the t statistic
IPT v. Pharmacotherapy ESs and NNTsIPT v. Pharmacotherapy ESs and NNTs
Author Population Design Duration Depression Measure
Effect Size1
Frank et al., 2011
Acute depression
IPT (n=160) v.ESCIT (n=158 )
Note: treatment preference had no effect on outcome
12 weeks Time to remission
ES= -.14NNT=-14.3
1ES calculated comparing IPT alone to pharmacotherapy alone based on arcsin transformations of two proportions, NNT the inverse of the difference in two proportions
SummarySummary• IPT has generally fared reasonably well in IPT has generally fared reasonably well in
comparison to pharmacotherapy of acute comparison to pharmacotherapy of acute depressiondepression
• More chronic conditions (recurrent depression More chronic conditions (recurrent depression and dysthymia) generally had somewhat and dysthymia) generally had somewhat better outcomes with pharmacotherapybetter outcomes with pharmacotherapy
• Study designs have shown increasing Study designs have shown increasing sophistication over the 30+ years of research sophistication over the 30+ years of research on IPT and pharmacotherapy, but no perfect on IPT and pharmacotherapy, but no perfect design existsdesign exists
• Clear tensions exist between ecological Clear tensions exist between ecological validity and research design rigorvalidity and research design rigor