Multiple Chronic Conditions in a Sample of Community- · For peer review only Multiple Chronic Conditions in a Sample of Community-Dwelling Adults with Fibromyalgia in Olmsted County,

For peer review only

Multiple Chronic Conditions in a Sample of Community-Dwelling Adults with Fibromyalgia in Olmsted County,

Minnesota

Journal: BMJ Open

Manuscript ID: bmjopen-2014-006681

Article Type: Research

Date Submitted by the Author: 19-Sep-2014

Complete List of Authors: Vincent, Ann; Mayo Clinic, Division of General Internal Medicine Whipple, Mary; Mayo Clinic, Division of General Internal Medicine McAllister, Samantha; Mayo Clinic, Division of General Internal Medicine

Aleman, Katherine; Mayo Clinic, Division of General Internal Medicine St Sauver, Jennifer; Mayo Clinic, Department of Health Sciences Research

<b>Primary Subject Heading</b>:

Rheumatology

Secondary Subject Heading: Epidemiology

Keywords: EPIDEMIOLOGY, INTERNAL MEDICINE, Rheumatology < INTERNAL MEDICINE

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Running Head: MULTIPLE CHRONIC CONDITIONS IN FIBROMYALGIA 1

Multiple Chronic Conditions in a Sample of Community-Dwelling Adults with

Fibromyalgia in Olmsted County, Minnesota

Ann Vincent, MD

Mary O. Whipple, BA, BSN, RN, CCRP

Samantha J. McAllister, BA

Katherine M. Aleman, BA

Jennifer L. St. Sauver, PhD

Affiliations: Division of General Internal Medicine (Dr. Vincent, Ms. Whipple, Ms. McAllister,

and Ms. Aleman), Department of Health Sciences Research (Dr. St. Sauver), Mayo Clinic, 200

First Street SW, Rochester, MN 55902

Correspondence: Ann Vincent, MD; 200 First Street SW, Rochester, MN 55902;

Phone: 507-284-8913; Fax: 507-284-5370; [email protected]

Keywords: fibromyalgia, chronic pain, multiple chronic conditions, epidemiology

Word count: 2335

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MULTIPLE CHRONIC CONDITIONS IN FIBROMYALGIA 2

Abstract

Objectives: The objective of this study was to evaluate the problem of multiple chronic

conditions and polypharmacy in patients with fibromyalgia.

Design: Retrospective medical record review.

Setting: Olmsted County, Minnesota.

Participants: 1111 adults with fibromyalgia.

Primary and Secondary Outcome Measures: Number and type of chronic medical and

psychiatric conditions, medication use

Results: Medical record review demonstrated that greater than 50% of the sample had seven or

more chronic conditions. Chronic joint pain/degenerative arthritis was the most frequent

comorbidity (88.7%), followed by depression (75.1%), migraines/chronic headaches (62.4%),

and anxiety (56.5%). Approximately 40% of patients were taking 3 or more medications for

symptoms of fibromyalgia. Sleep aids were the most commonly prescribed medications in our

sample (33.3%) followed by selective serotonin reuptake inhibitors (28.7%), opioids (22.4%)

and serotonin norepinephrine reuptake inhibitors (21.0%).

Conclusions: The results of our study highlight the problem of multiple chronic conditions and

high prevalence of polypharmacy in fibromyalgia. Clinicians who care for patients with

fibromyalgia should take into consideration the presence of multiple chronic conditions when

recommending medications.

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Article Summary

Strengths and limitations of this study:

- This is the first study to evaluate the presence of multiple chronic conditions in a large

sample of community-dwelling adults with fibromyalgia.

- Notably, greater than 50% of our sample had seven or more chronic conditions

- Given this was a community-sample in Olmsted County, Minnesota, the results of our

study may not be generalizable to other samples of patients.

- Additionally, we did not include all possible medical and psychiatric conditions in this

study.

- The results of our study highlight the problem of multiple chronic conditions in

fibromyalgia and indicate clinicians who care for patients with fibromyalgia should take

into consideration the presence of multiple chronic conditions.

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Introduction

The presence of multiple chronic conditions is increasingly recognized as a challenge in the

medical management of patients with chronic diseases including diabetes, heart disease, obesity,

and arthritis [1, 2]. Although most health care systems are excellent at managing individual

conditions, these systems are often ineffective in caring for patients with multiple chronic

conditions. This is because the care of patients with multiple chronic conditions must

simultaneously consider the interrelationship of different conditions and the implication of

medication choice on the patient’s other conditions. This complicates medical evaluation,

decision-making, and management [3, 4]. For example, the use of steroids to treat polymyalgia

rheumatica in a patient who also has type II diabetes, hypertension, and obesity requires more

complex decision-making than is guided by singular protocols that are currently in use. A

situation such as this is a common observation in clinical practice and is problematic as the

percentage of patients with multiple chronic conditions is steadily increasing [5].

Fibromyalgia is a chronic condition that is relatively common in clinical practice [6, 7] and is

associated with multiple chronic medical and psychiatric conditions. A small body of literature

has reported a high prevalence of headaches, irritable bowel syndrome, chronic fatigue,

rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, sleep disorders, hypertension,

type II diabetes, depression, and anxiety [8-12] in fibromyalgia, but the majority of these papers

focused on either medical or psychiatric conditions and/or disability. Furthermore, no

publications to date have considered the cumulative burden of multiple chronic conditions in

fibromyalgia. This is important because not only is fibromyalgia difficult to manage, but

fibromyalgia in combination with other chronic medical and psychiatric conditions substantially ,

amplifies a patient’s symptom burden and complicates the medical management for health care

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providers. This is further complicated by the use of multiple medications (with multiple side

effects) to manage pain and other symptoms in fibromyalgia, as many of the medications

employed frequently contribute to or exacerbate existing comorbidities [13-15].

Recognizing the presence of multiple chronic conditions and the potential for polypharmacy may

be one step towards improving the current, ineffective management of fibromyalgia. The

objective of this report is to describe the proportion of patients with multiple chronic conditions

and the proportion of patients using multiple medications related to fibromyalgia, in a cohort of

community-dwelling adults with fibromyalgia in Olmsted County, Minnesota.

Materials and Methods

This cross-sectional study utilized a sample of patients identified via the Rochester

Epidemiology Project and previously described [7]. Upon identification of eligible patients,

detailed medical record review was conducted to assess the presence of medical and psychiatric

conditions as outlined below.

The Rochester Epidemiology Project

The Rochester Epidemiology Project (REP) is a unique resource that indexes the medical records

of all residents who receive care in Olmsted County, Minnesota. In Olmsted County, all medical

care is provided by two medical facilities: Mayo Clinic and Olmsted Medical Center. Each

institution uses a unit (or dossier) medical record system, whereby data from an individual (e.g..

demographics, diagnoses, and billing records) are assembled in one place and are made available

for approved research studies under the umbrella of the REP [16, 17]. The majority of residents

receive care at more than one institution, resulting in multiple records to be reviewed for each

person. The REP maintains an index of the diagnostic codes obtained from all of the

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participating providers. The REP diagnostic index includes diagnostic codes from the

International Classification of Diseases (HICDA) for conditions identified by physicians during

office visits or hospital stays. This index can be searched to identify groups of patients with a

particular condition of interest in the Olmsted County population. This is a unique resource

captures virtually the entire Olmsted County population [18] and allows for comprehensive

medical record review.

Participants and Procedure

In this study, we utilized the REP to identify patients with fibromyalgia. To do so, we used the

REP diagnostic index to retrieve a list of all Olmsted County residents age 21 years and older

who had received a diagnosis of fibromyalgia (HICDA code 07893-21-3 or ICD-9 code 729.1

(myalgia, myositis, fibromyositis, or fibromyalgia)) between January 1, 2005, and December 31,

2009. Since these codes are not specific to fibromyalgia and include other diagnoses such as

myalgia and myositis, individual medical records of all of the patients retrieved (N=3410) in this

search were reviewed to confirm a diagnosis of fibromyalgia by a health care provider.

Additionally, medical records were reviewed to evaluate the presence of a number of medical

and psychiatric comorbidities most commonly reported in patients with fibromyalgia [8-12].

These included degenerative joint disease/arthritis, rheumatoid arthritis, systemic lupus

erythematosus, plantar fasciitis, migraines/chronic headaches, temporomandibular joint disorder,

chronic pelvic pain, endometriosis, irritable bowel, irritable bladder, anxiety, depression,

dysthymia, bipolar disorder, insomnia, restless legs syndrome, and metabolic syndrome. Given

the retrospective nature of this study and the limited variables available to define metabolic

syndrome, for the purpose of this study, metabolic syndrome was defined as the presence of two

of more of the following: body mass index (BMI) greater than 30, diabetes mellitus type 2,

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hypertension, and hyperlipidemia (REFS). Information regarding use of medications related to

fibromyalgia was also abstracted as of the reference date (December 31, 2012). These included

serotonin norepinephrine reuptake inhibitors (SNRI), alpha-2-delta ligands, tricyclic

antidepressants, selective serotonin reuptake inhibitors (SSRI), opioids, tramadol, skeletal

muscle relaxants, benzodiazepines, sleep aids, and other psychiatric medications. Sleep aids

included zolpidem, zaleplon, eszopiclone, trazodone, and melatonin. Other psychiatric

medications included lithium, monamine oxidase inhibitors, antipsychotics, bupropion,

lamotrigine, and tetracyclic antidepressants.

Statistical Analysis

Descriptive statistics were calculated from demographic variables and recorded as means and

standards deviations. The total number of patients with each chronic condition was determined

and reported as percent of the total sample. Similarly, the use of medications in each class as

documented in the medical record was reported as percent of the total sample. In order to

determine the number of patients with multiple conditions, a total number of chronic conditions

was determined for each patient. This process was repeated with medications.

This study was approved by the site’s Institutional Review Board and all participants provided

consent for use of their medical records for research.

Results

A total of 1111 patients had a diagnosis of fibromyalgia confirmed via medical record review.

Patients in this cohort had a mean age of 59.4 (standard deviation 14.2) and a mean BMI of 30.8

(standard deviation 7.7). As expected based on the prevalence of fibromyalgia in the general

population[6, 7], the majority of our sample was female (93.7%). The average duration of

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fibromyalgia, based on the date diagnosis first appeared in the medical record, was 11.1 years

(standard deviation 6.0).

Greater than 50% of the sample had seven or more chronic conditions (Fig. 1a). Chronic joint

pain/degenerative arthritis was the most frequent comorbidity (88.7%), followed by depression

(75.1%), migraines/chronic headaches (62.4%), and anxiety (56.5%). Of the sample, 50.5% met

criteria for metabolic syndrome. A list of all medical and psychiatric conditions abstracted are

reported in Table 1.

Table 1 Co-occurring medical conditions and prescription medications among fibromyalgia

patients

Characteristic N (%)

Medical Conditions

Chronic joint pain/Degenerative arthritis 986 [88.7]

Migraines/Chronic Headaches 693 [62.4]

Hyperlipidemia 562 [51.3]

Metabolic Syndrome (per criteria) 539 [50.5]

Obesity (BMI > 30) 519 [48.0]

Hypertension 508 [46.2]

Irritable Bowel 361 [32.5]

Plantar fasciitis 276 [24.8]

Diabetes Mellitus 196 [17.9]

Temporomandibular Joint Disorder 193 [17.4]

Chronic Pelvic Pain 170 [15.3]

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Endometriosis (confirmed, females only) 91 [8.7]

Rheumatoid Arthritis 59 [5.3]

Irritable Bladder 44 [4.0]

Systemic Lupus Erythematosus 17 [1.5]

Mental Health Conditions

Depression 834 [75.1]

Anxiety 628 [56.5]

Dysthymia 216 [19.4]

Bipolar Disorder 65 [5.9]

Sleep Conditions

Insomnia 562 [50.6]

Restless Legs Syndrome 225 [20.3]

Medications

Sleep aids 370 [33.3]

SSRI 319 [28.7]

Opioids 249 [22.4]

SNRI 233 [21.0]

Alpha-2-delta ligands 215 [19.4]

Benzodiazepines 214 [19.3]

aOther psychiatric medications 206 [18.5]

Tricyclic antidepressants 190 [17.1]

Tramadol 174 [15.7]

Skeletal muscle relaxants 167 [15.0]

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aOther psychiatric medications includes lithium, monamine oxidase inhibitors, antipsychotics,

bupropion, lamotrigine, and tetracyclic antidepressants.

Medication use is also reported in Table 1. Approximately 40% of patients were taking 3 or

more medications for symptoms of fibromyalgia (Fig. 1b). Sleep aids were the most commonly

prescribed medications in our sample (33.3%) followed by SSRIs (28.7%), opioids (22.4%) and

SNRIs (21.0%). Overall, 31.4% of our sample was taking either tramadol or an opioid.

We also evaluated conditions that co-occurred most frequently and medications that were used

most frequently together, as reported in Table 2.

Table 2 Most common combinations of conditions and medications in patients with fibromyalgia

Condition 1 Condition 2 N [%]

Chronic joint pain/Degenerative arthritis Depression 749 [67.4]

Chronic joint pain/Degenerative arthritis Chronic headaches/Migraines 628 [56.5]

Chronic joint pain/Degenerative arthritis Anxiety 569 [51.2]

Depression Anxiety 560 [50.4]

Depression Chronic headaches/Migraines 553 [49.8]

Chronic joint pain/Degenerative arthritis Insomnia 524 [47.2]

Chronic joint pain/Degenerative arthritis Obesity (BMI >30) 467 [43.2]

Chronic joint pain/Degenerative arthritis Hypertension 473 [43.0]

Medication 1 Medication 2

Sleep aids SSRI 130 [11.7]

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Sleep aids Opioids 103 [9.3]

Sleep aids aOther psychiatric medications 101 [9.1]

Sleep aids SNRI 97 [8.7]

Sleep aids Alpha-2-delta ligands 92 [8.3]

Opioids SSRI 88 [7.9]

Sleep aids Tramadol 85 [7.7]

Sleep aids Benzodiazepines 80 [7.2]



The conditions that most commonly occurred together were chronic joint pain/degenerative

arthritis and depression (67.4%), followed by chronic joint pain/degenerative arthritis and

migraines/chronic headaches (56.5%), and chronic joint pain/degenerative arthritis and anxiety

(51.2%). The medications that were used most frequently together were sleep aids and SSRI

(11.7%), sleep aids and opioids (9.3%), and sleep aids and other psychiatric medications (9.1%).

Discussion

The results of our study highlight the problem of multiple chronic conditions in fibromyalgia.

Notably, greater than 50% of our sample had seven or more chronic conditions and the most

frequent of those were other pain disorders (chronic joint pain/degenerative arthritis and

migraines/chronic headaches), depression, and anxiety. Given that the presence of unrefreshing

sleep is included in the 2010 fibromyalgia diagnostic criteria [19], it was not surprising that a

high percentage (over 50%) of our sample had a diagnosis of insomnia. While a high prevalence

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of obesity in fibromyalgia has been previously reported [20-22] and is present in our sample, we

did not expect to observe so many cases of hypertension, hyperlipidemia, and diabetes mellitus

that resulted in over 50% of our sample meeting criteria for metabolic syndrome. Our results add

to the growing body of evidence regarding the importance of considering the cumulative burden

of multiple chronic conditions in fibromyalgia.

The presence of other pain conditions and anxiety and depressive disorders can contribute to the

overall symptom burden in individual patients with fibromyalgia. Having fibromyalgia, in itself,

is challenging for patients, due to the lack of effective management modalities. When this

problem is exacerbated by the presence of other pain disorders, the burden of pain to a patient

with fibromyalgia is increased. Further complicating this is the high prevalence of depression

and anxiety in fibromyalgia, which can amplify fibromyalgia symptoms and make it difficult to

sort out causal relationships. For example, in order to effectively manage insomnia, it would be

useful to determine whether the insomnia is results from depression or sleep disturbance from

pain. If clinical management of fibromyalgia is to be most effective, evaluations should also take

into consideration the assessment and management of multiple chronic conditions that also

influence a patient’s overall symptom burden.

Another important finding in our study was the high prevalence of the use of multiple

medications in fibromyalgia. Although pain, anxiety, and depression were the most common

chronic conditions, sleep aids were the most commonly prescribed medications in our sample.

This may be reflective of the bidirectional relationship of sleep with pain, anxiety, and

depression. Additionally, greater than 40% of the sample was prescribed three or more

medications for fibromyalgia management, and interestingly, greater than 10% were prescribed 5

or more medications for symptom management. This is concerning in that although these

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medications may have therapeutic effects, the side effects of these medications could contribute

to worsening comorbidity. For example, SNRIs that are FDA-approved for fibromyalgia have

both weight gain and increased blood pressure as side effects [13, 15]. Although the use of these

medications to lower pain and improve mood in fibromyalgia may be appropriate, their use could

exacerbate other chronic conditions such as hypertension and obesity. Also, increased weight,

through its physical effects on joints, could worsen chronic joint pain/degenerative arthritis.

Interestingly, a large percentage of patients were using opioids (22.4%), despite the lack of

definitive data supporting their use in fibromyalgia. This indicates the challenge of effectively

managing chronic pain in this population. A large percentage of patients were also using

benzodiazepines (19.3%), although it was unclear whether they were prescribed for anxiety,

sleep, or both. The use sedating medications such as opioids and benzodiazepines in patients

with fibromyalgia with sleep disorders (e.g. sleep disordered breathing) could be problematic.

Therefore, the influence of a multiple medications on a patient’s multiple chronic conditions

should be considered prior to prescribing.

This study was unique in that use of the REP allowed us conduct exhaustive medical record

review in a large sample of community-dwelling adults with fibromyalgia. However, the results

of our study may not be generalizable to other samples of patients with very different

characteristics. Additionally, as we were primarily interested in evaluating the presence of

chronic medical conditions that were commonly observed in the clinical care of patients with

fibromyalgia, we did not include all possible medical and psychiatric conditions in this study.

Despite these potential limitations, this report of multiple chronic conditions and medication use

in a community-dwelling sample of patients with fibromyalgia adds substantially to the

literature.

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To conclude, multiple chronic conditions and the use of multiple medications are highly

prevalent in patients with fibromyalgia and pose a unique challenge to the management of this

condition. Clinicians who care for patients with fibromyalgia should take into consideration the

presence of multiple chronic conditions when recommending medications. Furthermore, properly

addressing these multiple chronic conditions may mitigate the patient’s overall illness burden.

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Acknowledgements

Study data were collected and managed using REDCap electronic data capture tools hosted at

Mayo Clinic REDCap (Research Electronic Data Capture) is a secure, web-based application

designed to support data capture for research studies, providing 1) an intuitive interface for

validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3)

automated export procedures for seamless data downloads to common statistical packages; and

4) procedures for importing data from external sources.

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Funding Statement

This study was made possible using the resources of the Rochester Epidemiology Project, which

is supported by the National Institute on Aging of the National Institutes of Health under Award

Number R01AG034676. The content is solely the responsibility of the authors and does not

necessarily represent the official views of the National Institutes of Health.

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Contributorship Statement

Conception and design (AV, MOW, JLS); acquisition, analysis or interpretation of data (AV,

MOW, SJM, KMA, JLS); drafting the work or revising it critically for important intellectual

content; final approval of the version to be published (AV, MOW, SJM, KMA, JLS); agreement

to accountable for all aspects of the work in ensuring that questions related to the accuracy or

integrity of any part of the work are appropriately investigated and resolved (AV, MOW, SJM,

KMA, JLS)

Competing Interests

The authors declare they have no conflict of interest.

Data Sharing Statement

There are no additional, unpublished data.

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17 St Sauver JL, Grossardt BR, Yawn BP, et al. Data resource profile: the Rochester

Epidemiology Project (REP) medical records-linkage system. Int J Epidemiol

2012;41(6):1614-1624.

18 St Sauver JL, Grossardt BR, Yawn BP, et al. Use of a medical records linkage system to

enumerate a dynamic population over time: the Rochester Epidemiology Project. Am J

Epidemiol 2011;173(9):1059-1068.

19 Wolfe F, Clauw DJ, Fitzcharles M-A, et al. Fibromyalgia criteria and severity scales for

clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic

Criteria for Fibromyalgia. J Rheumatol 2011;38(6):1113-1122.

20 Okifuji A, Donaldson GW, Barck L, et al. Relationship between fibromyalgia and obesity in

pain, function, mood, and sleep. J Pain 2010;11(12):1329-1337.

21 Ursini F, Naty S, Grembiale RD. Fibromyalgia and obesity: the hidden link. Rheumatol Int

2011;31(11):1403-1408.

22 Yunus MB, Arslan S, Aldag JC. Relationship between body mass index and fibromyalgia

features. Scand J Rheumatol 2002;31(1):27-31.

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Fig. 1 Pie charts demonstrating the proportion of patient with fibromyalgia that have multiple

comorbidities (panel a) and proportion of patients that are taking multiple medications (panel b)

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Author Contributions






KMA, JLS)

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254x93mm (96 x 96 DPI)

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STROBE 2007 (v4) Statement—Checklist of items that should be included in reports of cross-sectional studies

Section/Topic Item

# Recommendation Reported on page #

Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract 1

(b) Provide in the abstract an informative and balanced summary of what was done and what was found 2

Introduction

Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 6-7

Objectives 3 State specific objectives, including any prespecified hypotheses 7

Methods

Study design 4 Present key elements of study design early in the paper 7

Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data

collection

7-8

Participants

6

(a) Give the eligibility criteria, and the sources and methods of selection of participants 8

Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if

applicable

8-9

Data sources/

measurement

8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe

comparability of assessment methods if there is more than one group

8-9

Bias 9 Describe any efforts to address potential sources of bias NA since this was a

medical record

review

Study size 10 Explain how the study size was arrived at 8-9

Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and

why

Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 9

(b) Describe any methods used to examine subgroups and interactions 9

(c) Explain how missing data were addressed NA

(d) If applicable, describe analytical methods taking account of sampling strategy 7

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(e) Describe any sensitivity analyses NA

Results

Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility,

confirmed eligible, included in the study, completing follow-up, and analysed

8-9

(b) Give reasons for non-participation at each stage NA medical record

review

(c) Consider use of a flow diagram NA

Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential

confounders

9

(b) Indicate number of participants with missing data for each variable of interest NA

Outcome data 15* Report numbers of outcome events or summary measures 9-13

Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence

interval). Make clear which confounders were adjusted for and why they were included

NA

(b) Report category boundaries when continuous variables were categorized 10

(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period NA

Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses NA

Discussion

Key results 18 Summarise key results with reference to study objectives 13

Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and

magnitude of any potential bias

15

Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from

similar studies, and other relevant evidence

15

Generalisability 21 Discuss the generalisability (external validity) of the study results 15

Other information

Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on

which the present article is based

4

*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.

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Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE

checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at

http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.

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A Cross-Sectional Assessment of the Prevalence of Multiple Chronic Conditions and Medication Use in a Sample of

Community-Dwelling Adults with Fibromyalgia in Olmsted County, Minnesota

Journal: BMJ Open

Manuscript ID: bmjopen-2014-006681.R1

Article Type: Research

Date Submitted by the Author: 02-Jan-2015

Complete List of Authors: Vincent, Ann; Mayo Clinic, Division of General Internal Medicine Whipple, Mary; Mayo Clinic, Division of General Internal Medicine McAllister, Samantha; Mayo Clinic, Division of General Internal Medicine Aleman, Katherine; Mayo Clinic, Division of General Internal Medicine St Sauver, Jennifer; Mayo Clinic, Department of Health Sciences Research

<b>Primary Subject Heading</b>:

Rheumatology

Secondary Subject Heading: Epidemiology

Keywords: EPIDEMIOLOGY, INTERNAL MEDICINE, Rheumatology < INTERNAL MEDICINE


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Running Head: MULTIPLE CHRONIC CONDITIONS IN FIBROMYALGIA 1

A Cross-Sectional Assessment of the Prevalence of Multiple Chronic Conditions and

Medication Use in a Sample of Community-Dwelling Adults with Fibromyalgia in Olmsted

County, Minnesota

Ann Vincent, MD

Mary O. Whipple, BA, BSN, RN, CCRP

Samantha J. McAllister, BA

Katherine M. Aleman, BA

Jennifer L. St. Sauver, PhD

Affiliations: Division of General Internal Medicine (Dr. Vincent, Ms. Whipple, Ms. McAllister,

and Ms. Aleman), Department of Health Sciences Research (Dr. St. Sauver), Mayo Clinic, 200

First Street SW, Rochester, MN 55902

Correspondence: Ann Vincent, MD; 200 First Street SW, Rochester, MN 55902;

Phone: 507-284-8913; Fax: 507-284-5370; [email protected]

Keywords: fibromyalgia, chronic pain, multiple chronic conditions, epidemiology

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Word count: 24355

Abstract

Objectives: The objective of this study was to evaluate the problem of multiple chronic

conditions and polypharmacy in patients with fibromyalgia.

Design: Retrospective medical record review.

Setting: Olmsted County, Minnesota.

Participants: 1111 adults with fibromyalgia.

Primary and Secondary Outcome Measures: Number and type of chronic medical and

psychiatric conditions, medication use

Results: Medical record review demonstrated that greater than 50% of the sample had seven or

more chronic conditions. Chronic joint pain/degenerative arthritis was the most frequent

comorbidity (88.7%), followed by depression (75.1%), migraines/chronic headaches (62.4%),

and anxiety (56.5%). Approximately 40% of patients were taking 3 or more medications for

symptoms of fibromyalgia. Sleep aids were the most commonly prescribed medications in our

sample (33.3%) followed by selective serotonin reuptake inhibitors (28.7%), opioids (22.4%)

and serotonin norepinephrine reuptake inhibitors (21.0%).

Conclusions: The results of our study highlight the problem of multiple chronic conditions and

high prevalence of polypharmacy in fibromyalgia. Clinicians who care for patients with

fibromyalgia should take into consideration the presence of multiple chronic conditions when

recommending medications.

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Article Summary

Strengths and limitations of this study:

- This is the first study to evaluate the presence of multiple chronic conditions in a large

sample of community-dwelling adults with fibromyalgia.

- Notably, greater than 50% of our sample had seven or more chronic conditions

- Given this was a community-sample in Olmsted County, Minnesota, the results of our

study may not be generalizable to other samples of patients.

- Additionally, we did not include all possible medical and psychiatric conditions in this

study.

- The results of our study highlight the problem of multiple chronic conditions in

fibromyalgia and indicate clinicians who care for patients with fibromyalgia should take

into consideration the presence of multiple chronic conditions.

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Funding Statement

This study was made possible using the resources of the Rochester Epidemiology Project, which

is supported by the National Institute on Aging of the National Institutes of Health under Award

Number R01AG034676. The content is solely the responsibility of the authors and does not

necessarily represent the official views of the National Institutes of Health.

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Competing Interests

The authors declare they have no conflict of interest.

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Introduction

The presence of multiple chronic conditions is increasingly recognized as a challenge in the

medical management of patients with chronic diseases including diabetes, heart disease, obesity,

and arthritis [1, 2]. Although most health care systems are excellent at managing individual

conditions, these systems are often ineffective in caring for patients with multiple chronic

conditions. This is because the care of patients with multiple chronic conditions must

simultaneously consider the interrelationship of different conditions and the implication of

medication choice on the patient’s other conditions. This complicates medical evaluation,

decision-making, and management [3, 4]. For example, the use of steroids to treat polymyalgia

rheumatica in a patient who also has type II diabetes, hypertension, and obesity requires more

complex decision-making than is guided by singular protocols that are currently in use. A

situation such as this is a common observation in clinical practice and is problematic as the

percentage of patients with multiple chronic conditions is steadily increasing [5].

Fibromyalgia is a chronic condition that is relatively common in clinical practice [6, 7] and is

associated with multiple chronic medical and psychiatric conditions. A small body of literature

has reported a high prevalence of headaches, irritable bowel syndrome, chronic fatigue,

rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, sleep disorders, hypertension,

type II diabetes, depression, and anxiety [8-12] in fibromyalgia, but the majority of these papers

focused on either medical or psychiatric conditions and/or disability. Furthermore, no

publications to date have considered the cumulative burden of multiple chronic conditions in

fibromyalgia. This is important because not only is fibromyalgia difficult to manage, but

fibromyalgia in combination with other chronic medical and psychiatric conditions substantially ,

amplifies a patient’s symptom burden and complicates the medical management for health care

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providers. This is further complicated by the use of multiple medications (with multiple side

effects) to manage pain and other symptoms in fibromyalgia, as many of the medications

employed frequently contribute to or exacerbate existing comorbidities [13-15].

Recognizing the presence of multiple chronic conditions and the potential for polypharmacy may

be one step towards improving the current, ineffective management of fibromyalgia. The

objective of this report is to describe the proportion of patients with multiple chronic conditions

and the proportion of patients using multiple medications related to fibromyalgia, in a cohort of

community-dwelling adults with fibromyalgia in Olmsted County, Minnesota.

Materials and Methods

This cross-sectional study utilized a sample of patients identified via the Rochester

Epidemiology Project and previously described [7]. Upon identification of eligible patients,

detailed medical record review was conducted to assess the presence of medical and psychiatric

conditions as outlined below.

The Rochester Epidemiology Project

The Rochester Epidemiology Project (REP) is a unique resource that indexes the medical records

of all residents who receive care in Olmsted County, Minnesota. In Olmsted County, all medical

care is provided by two medical facilities: Mayo Clinic and Olmsted Medical Center. Each

institution uses a unit (or dossier) medical record system, whereby data from an individual (e.g..

demographics, diagnoses, and billing records) are assembled in one place and are made available

for approved research studies under the umbrella of the REP [16, 17]. The majority of residents

receive care at more than one institution, resulting in multiple records to be reviewed for each

person. The REP maintains an index of the diagnostic codes obtained from all of the

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participating providers. The REP diagnostic index includes diagnostic codes from the

International Classification of Diseases (HICDA) for conditions identified by physicians during

office visits or hospital stays. This index can be searched to identify groups of patients with a

particular condition of interest in the Olmsted County population. This is a unique resource

captures virtually the entire Olmsted County population [18] and allows for comprehensive

medical record review.

Participants and Procedure

In this study, we utilized the REP to identify patients with fibromyalgia. To do so, we used the

REP diagnostic index to retrieve a list of all Olmsted County residents age 21 years and older

who had received a diagnosis of fibromyalgia (HICDA code 07893-21-3 or ICD-9 code 729.1

(myalgia, myositis, fibromyositis, or fibromyalgia)) between January 1, 2005, and December 31,

2009. Since these codes are not specific to fibromyalgia and include other diagnoses such as

myalgia and myositis, individual medical records of all of the patients retrieved in this search

were reviewed to confirm a diagnosis of fibromyalgia by a health care provider. Of the 3410

patients identified, 86 declined authorization for medical record review. Medical records were

reviewed to evaluate the presence of a number of medical and psychiatric comorbidities most

commonly reported in patients with fibromyalgia [8-12]. These included degenerative joint

disease/arthritis, rheumatoid arthritis, systemic lupus erythematosus, plantar fasciitis,

migraines/chronic headaches, temporomandibular joint disorder, chronic pelvic pain,

endometriosis, irritable bowel, irritable bladder, anxiety, depression, dysthymia, bipolar disorder,

insomnia, restless legs syndrome, and metabolic syndrome. Given the retrospective nature of this

study and the limited variables available to define metabolic syndrome, for the purpose of this

study, metabolic syndrome was defined as the presence of two of more of the following: body

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mass index (BMI) greater than 30, diabetes mellitus type 2, hypertension, and hyperlipidemia

(REFS). Information regarding use of medications related to fibromyalgia was also abstracted as

of the reference date (December 31, 2012). These included serotonin norepinephrine reuptake

inhibitors (SNRI), alpha-2-delta ligands, tricyclic antidepressants, selective serotonin reuptake

inhibitors (SSRI), opioids, tramadol, skeletal muscle relaxants, benzodiazepines, sleep aids, and

other psychiatric medications. Sleep aids included zolpidem, zaleplon, eszopiclone, trazodone,

and melatonin. Other psychiatric medications included lithium, monamine oxidase inhibitors,

antipsychotics, bupropion, lamotrigine, and tetracyclic antidepressants.

Statistical Analysis

Descriptive statistics were calculated from demographic variables and recorded as means and

standards deviations. The total number of patients with each chronic condition was determined

and reported as percent of the total sample. Similarly, the use of medications in each class as

documented in the medical record was reported as percent of the total sample. In order to

determine the number of patients with multiple conditions, a total number of chronic conditions

was determined for each patient. This process was repeated with medications.

This study was approved by the site’s Institutional Review Board and all participants provided

consent for use of their medical records for research.

Results

A total of 1111 patients had a diagnosis of fibromyalgia confirmed via medical record review.

Patients in this cohort had a mean age of 59.4 (standard deviation 14.2) and a mean BMI of 30.8

(standard deviation 7.7). As expected based on the prevalence of fibromyalgia in the general

population[6, 7], the majority of our sample was female (93.7%). The average duration of

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fibromyalgia, based on the date diagnosis first appeared in the medical record, was 11.1 years

(standard deviation 6.0).

Greater than 50% of the sample had seven or more chronic conditions (Fig. 1a). Chronic joint

pain/degenerative arthritis was the most frequent comorbidity (88.7%), followed by depression

(75.1%), migraines/chronic headaches (62.4%), and anxiety (56.5%). Of the sample, 50.5% met

criteria for metabolic syndrome. A list of all medical and psychiatric conditions abstracted are

reported in Table 1.

Table 1 Co-occurring medical conditions and prescription medications among fibromyalgia

patients

Characteristic N (%)

Medical Conditions

Chronic joint pain/Degenerative arthritis 986 [88.7]

Migraines/Chronic Headaches 693 [62.4]

Hyperlipidemia 562 [51.3]

Obesity (BMI > 30) 519 [48.0]

Hypertension 508 [46.2]

Irritable Bowel 361 [32.5]

Plantar fasciitis 276 [24.8]

Diabetes Mellitus, type II 196 [17.9]

Temporomandibular Joint Disorder 193 [17.4]

Chronic Pelvic Pain 170 [15.3]

Endometriosis (confirmed, females only) 91 [8.2]

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Rheumatoid Arthritis 59 [5.3]

Irritable Bladder 44 [4.0]

Systemic Lupus Erythematosus 17 [1.5]

Mental Health Conditions

Depression 834 [75.1]

Anxiety 628 [56.5]

Dysthymia 216 [19.4]

Bipolar Disorder 65 [5.9]

Sleep Conditions

Insomnia 562 [50.6]

Restless Legs Syndrome 225 [20.3]

Medications

Sleep aids 370 [33.3]

SSRI 319 [28.7]

Opioids 249 [22.4]

SNRI 233 [21.0]

Alpha-2-delta ligands 215 [19.4]

Benzodiazepines 214 [19.3]

aOther psychiatric medications 206 [18.5]

Tricyclic antidepressants 190 [17.1]

Tramadol 174 [15.7]

Skeletal muscle relaxants 167 [15.0]

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Medication use is also reported in Table 1. Approximately 40% of patients were taking 3 or

more medications for symptoms of fibromyalgia (Fig. 1b). Sleep aids were the most commonly

prescribed medications in our sample (33.3%) followed by SSRIs (28.7%), opioids (22.4%) and

SNRIs (21.0%). Overall, 31.4% of our sample was taking either tramadol or an opioid.

We also evaluated conditions that co-occurred most frequently and medications that were used

most frequently together, as reported in Table 2.

Table 2 Most common combinations of conditions and medications in patients with fibromyalgia

Condition 1 Condition 2 N [%]

Chronic joint pain/Degenerative arthritis Depression 749 [67.4]

Chronic joint pain/Degenerative arthritis Chronic headaches/Migraines 628 [56.5]

Chronic joint pain/Degenerative arthritis Anxiety 569 [51.2]

Depression Anxiety 560 [50.4]

Depression Chronic headaches/Migraines 553 [49.8]

Chronic joint pain/Degenerative arthritis Insomnia 524 [47.2]

Chronic joint pain/Degenerative arthritis Obesity (BMI >30) 467 [43.2]

Chronic joint pain/Degenerative arthritis Hypertension 473 [43.0]

Medication 1 Medication 2

Sleep aids SSRI 130 [11.7]

Sleep aids Opioids 103 [9.3]

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Sleep aids aOther psychiatric medications 101 [9.1]

Sleep aids SNRI 97 [8.7]

Sleep aids Alpha-2-delta ligands 92 [8.3]

Opioids SSRI 88 [7.9]

Sleep aids Tramadol 85 [7.7]

Sleep aids Benzodiazepines 80 [7.2]



The conditions that most commonly occurred together were chronic joint pain/degenerative

arthritis and depression (67.4%), followed by chronic joint pain/degenerative arthritis and

migraines/chronic headaches (56.5%), and chronic joint pain/degenerative arthritis and anxiety

(51.2%). The medications that were used most frequently together were sleep aids and SSRI

(11.7%), sleep aids and opioids (9.3%), and sleep aids and other psychiatric medications (9.1%).

Discussion

The results of our study highlight the problem of multiple chronic conditions in fibromyalgia.

Notably, greater than 50% of our sample had seven or more chronic conditions and the most

frequent of those were other pain disorders (chronic joint pain/degenerative arthritis and

migraines/chronic headaches), depression, and anxiety. Given that the presence of unrefreshing

sleep is included in the 2010 fibromyalgia diagnostic criteria [19], it was not surprising that a

high percentage (over 50%) of our sample had a diagnosis of insomnia. While a high prevalence

of obesity in fibromyalgia has been previously reported [20-22] and is present in our sample, we

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did not expect to observe so many cases of hypertension, hyperlipidemia, and diabetes mellitus

that resulted in over 50% of our sample meeting criteria for metabolic syndrome. Our results add

to the growing body of evidence regarding the importance of considering the cumulative burden

of multiple chronic conditions in fibromyalgia.

The presence of other pain conditions and anxiety and depressive disorders can contribute to the

overall symptom burden in individual patients with fibromyalgia. Having fibromyalgia, in itself,

is challenging for patients, due to the lack of effective management modalities. When this

problem is exacerbated by the presence of other pain disorders, the burden of pain to a patient

with fibromyalgia is increased. Further complicating this is the high prevalence of depression

and anxiety in fibromyalgia, which can amplify fibromyalgia symptoms and make it difficult to

sort out causal relationships. For example, in order to effectively manage insomnia, it would be

useful to determine whether the insomnia is results from depression or sleep disturbance from

pain. If clinical management of fibromyalgia is to be most effective, evaluations should also take

into consideration the assessment and management of multiple chronic conditions that also

influence a patient’s overall symptom burden.

Another important finding in our study was the high prevalence of the use of multiple

medications in fibromyalgia. Although pain, anxiety, and depression were the most common

chronic conditions, sleep aids were the most commonly prescribed medications in our sample.

This may be reflective of the bidirectional relationship of sleep with pain, anxiety, and

depression. Additionally, greater than 40% of the sample was prescribed three or more

medications for fibromyalgia management, and interestingly, greater than 10% were prescribed 5

or more medications for symptom management. This is concerning in that although these

medications may have therapeutic effects, the side effects of these medications could contribute

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to worsening comorbidity. For example, SNRIs that are FDA-approved for fibromyalgia have

both weight gain and increased blood pressure as side effects [13, 15]. Although the use of these

medications to lower pain and improve mood in fibromyalgia may be appropriate, their use could

exacerbate other chronic conditions such as hypertension and obesity. Also, increased weight,

through its physical effects on joints, could worsen chronic joint pain/degenerative arthritis.

Interestingly, a large percentage of patients were using opioids (22.4%), despite the lack of

definitive data supporting their use in fibromyalgia. This indicates the challenge of effectively

managing chronic pain in this population. A large percentage of patients were also using

benzodiazepines (19.3%), although it was unclear whether they were prescribed for anxiety,

sleep, or both. The use sedating medications such as opioids and benzodiazepines in patients

with fibromyalgia with sleep disorders (e.g. sleep disordered breathing) could be problematic.

Therefore, the influence of a multiple medications on a patient’s multiple chronic conditions

should be considered prior to prescribing.

A recent paper by Rocca et al. provides estimates of the prevalence of five of the chronic

conditions also assessed in our study in general population of Olmsted County [23]. Among

those age 50-69 years in the general population, the prevalence of arthritis, hyperlipidemia,

hypertension, diabetes, and depression was 13.2-22.2%, 33.2-50.6%, 23.8-42.9%, 15.9-26.6%,

and 12.0-14.5%, respectively. Except for diabetes, these conditions appear to be more common

in our sample of patients with fibromyalgia.

This study was unique in that use of the REP allowed us conduct exhaustive medical record

review in a large sample of community-dwelling adults with fibromyalgia. However, the results

of our study may not be generalizable to other samples of patients with very different

characteristics. Additionally, as we were primarily interested in evaluating the presence of

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chronic medical conditions that were commonly observed in the clinical care of patients with

fibromyalgia, we did not include all possible medical and psychiatric conditions in this study.

Another limitation is that as 86 of the 3410 patients originally identified did not provide

authorization for researchers to use their medical records, and therefore could not be included in

the medical record review, which is a potential source of bias. Despite these potential limitations,

this report of multiple chronic conditions and medication use in a community-dwelling sample of

patients with fibromyalgia adds substantially to the literature.

To conclude, multiple chronic conditions and the use of multiple medications are highly

prevalent in patients with fibromyalgia and pose a unique challenge to the management of this

condition. Clinicians who care for patients with fibromyalgia should take into consideration the

presence of multiple chronic conditions when recommending medications. Furthermore, properly

addressing these multiple chronic conditions may mitigate the patient’s overall illness burden.

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Acknowledgements

Study data were collected and managed using REDCap electronic data capture tools hosted at

Mayo Clinic REDCap (Research Electronic Data Capture) is a secure, web-based application

designed to support data capture for research studies, providing 1) an intuitive interface for

validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3)

automated export procedures for seamless data downloads to common statistical packages; and

4) procedures for importing data from external sources.

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Fig. 1 Pie charts demonstrating the percentage of patients with fibromyalgia who have multiple

comorbidities (panel a) and the percentage of patients who are taking multiple medications

(panel b)

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Author Contributions






KMA, JLS)

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254x90mm (300 x 300 DPI)

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STROBE 2007 (v4) Statement—Checklist of items that should be included in reports of cross-sectional studies

Section/Topic Item

# Recommendation Reported on page #

Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract 1

(b) Provide in the abstract an informative and balanced summary of what was done and what was found 2

Introduction

Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 6-7

Objectives 3 State specific objectives, including any prespecified hypotheses 7

Methods

Study design 4 Present key elements of study design early in the paper 7

Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data

collection

7-8

Participants

6

(a) Give the eligibility criteria, and the sources and methods of selection of participants 8

Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if

applicable

8-9

Data sources/

measurement

8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe

comparability of assessment methods if there is more than one group

8-9

Bias 9 Describe any efforts to address potential sources of bias NA since this was a

medical record

review15

Study size 10 Explain how the study size was arrived at 8-9

Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and

why

Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 9

(b) Describe any methods used to examine subgroups and interactions 9

(c) Explain how missing data were addressed NA

(d) If applicable, describe analytical methods taking account of sampling strategy 7

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(e) Describe any sensitivity analyses NA

Results

Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility,

confirmed eligible, included in the study, completing follow-up, and analysed

8-9

(b) Give reasons for non-participation at each stage NA medical record

review8

(c) Consider use of a flow diagram NA

Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential

confounders

9

(b) Indicate number of participants with missing data for each variable of interest NA

Outcome data 15* Report numbers of outcome events or summary measures 9-13

Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence

interval). Make clear which confounders were adjusted for and why they were included

NA

(b) Report category boundaries when continuous variables were categorized 10

(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period NA

Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses NA

Discussion

Key results 18 Summarise key results with reference to study objectives 13

Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and

magnitude of any potential bias

15

Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from

similar studies, and other relevant evidence

15

Generalisability 21 Discuss the generalisability (external validity) of the study results 15

Other information

Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on

which the present article is based

4

*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.

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Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE

checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at

http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.

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Multiple Chronic Conditions in a Sample of Community- · For peer review only Multiple Chronic Conditions in a Sample of Community-Dwelling Adults with Fibromyalgia in Olmsted County,

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