Seminars in Arthritis and Rheumatism 51 (2021) 166 174

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Seminars in Arthritis and Rheumatism

journal homepage: www.elsevier.com/locate/semarthrit

The Prevalence of Psychiatric and Chronic Pain Comorbidities in

Fibromyalgia: an ACTTION systematic review
Bethea A. Kleykampa,*,1, McKenzie C. Fergusonb,6, Ewan McNicolc, Ida Bixhoc,d,
Lesley M. Arnolde,2, Robert R. Edwardsf, Roger Fillingimg,3, Hanna Grol-Prokopczykh,
Dennis C. Turki,4, Robert H. Dworkina,5
a
University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
b
Southern Illinois University Edwardsville, School of Pharmacy, Edwardsville, IL, USA
c
MCPHS University, Boston, MA, USA
d
Sanofi Genzyme, Cambridge, MA, USA
e
University of Cincinnati College of Medicine, Cincinnati, OH, USA
f
Harvard Medical School, Boston, MA, USA
g
University of Florida, College of Dentistry, and Pain Research and Intervention Center of Excellence, Gainesville, FL, USA
h
University at Buffalo, SUNY, Buffalo, NY, USA
i
University of Washington, Seattle, WA, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Fibromyalgia (FM) is a chronic widespread pain condition that overlaps with multiple comorbid health con-
Central Sensitization ditions and contributes to considerable patient distress. The aim of this review was to provide a systematic
Co-morbidities overview of psychiatric and chronic pain comorbidities among patients diagnosed with FM and to inform the
Clinical Trial Design development of recommendations for the design of clinical trials. Thirty-one, cross-sectional, clinical epide-
Fibromyalgia
miology studies that evaluated patients diagnosed with FM were included for review. None of the reviewed
Psychiatric Disorders
studies reported on the incidence of these comorbidities. Sample size-weighted prevalence estimates were
calculated when prevalence data were reported in 2 or more studies for the same comorbid condition. The
most prevalent comorbidity across all studies reviewed was depression/major depressive disorder (MDD)
with over half of the patients included having this diagnosis in their lifetime (weighted prevalence up to
63%). In addition, nearly one-third of FM patients examined had current or lifetime bipolar disorder, panic
disorder, or post-traumatic stress disorder. Less common psychiatric disorders reported included generalized
anxiety disorder, obsessive compulsive disorder, and specific phobias (agoraphobia, social phobia). There
were fewer studies that examined chronic pain comorbidities among FM patients, but when evaluated, prev-
alence was also high ranging from 39% to 76% (i.e., chronic tension-type or migraine headache, irritable
bowel syndrome, myofascial pain syndrome, and temporomandibular disorders). The results of the review

Financial Support and DisclosuresPreparation of this systematic review was supported by ACTTION. ACTTION has received contracts, grants, or other revenue from the US Food
and Drug Administration (FDA), multiple pharmaceutical and device companies, philanthropy, and other sources. The views expressed in this article are those of the authors and no
official endorsement by the FDA or the pharmaceutical and device companies that provided unrestricted grants to support the activities of the ACTTION public-private partnership
should be inferred. Disclosures and conflict of interest statements by individual authors are as follows:
* Corresponding author. Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY, 14642, USA
E-mail address: bethea_kleykamp@urmc.rochester.edu (B.A. Kleykamp).
1
Bethea A. Kleykamp has received compensation in the past 36 months from Hayes, Inc./TractManager, Palladian Associates, and PinneyAssociates for contract or full-time medi-
cal writing on topics unrelated to the present review.
6
McKenzie Ferguson, Ewan McNicol, Ida Bixho, Robert Edwards, and Hanna Grol-Prokopczyk have no disclosures.
2
Lesley M. Arnold has received in the past 36 months support from research grants from Pfizer, Eli Lilly, Daiichi Sankyo, Teva, Allergan, Aptinyx, Axsome, and Tonix, and compen-
sation for consulting on clinical trials from Pfizer, Eli Lilly, Daiichi Sankyo, Zynerba, Astellas, Cinrx, Prismic, Teva, and Allergan.
3
Roger B. Fillingim has received in the past 36 months research support from the National Institutes of Health.
4
Dennis C. Turk has received in the past 36 months support from research grants and contracts from US Food and Drug Administration, US National Institutes of Health, and the
Patient Centered Outcomes Research Institute, and compensation for consulting on research methods and reporting from AccelRx, Eli Lilly, Flexion, GlaxoSmithKline, Novartis, and
Pfizer.
5
Robert H. Dworkin, PhD, has received in the past 5 years research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health, and
compensation for serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Astra-
Zeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Concert, Coronado, Daiichi Sankyo, Decibel, Dong-A, Editas, Eli Lilly, Eupraxia, Glen-
mark, Grace, Hope, Hydra, Immune, Johnson & Johnson, Lotus Clinical Research, Mainstay, Medavante, Merck, Neumentum, Neurana, NeuroBo, Novaremed, Novartis, NSGene,
Olatec, Periphagen, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy (also equity), Relmada, Sanifit, Scilex, Semnur, SK Life Sciences, Sollis, Spinifex, Syntrix, Teva, Thar,
Theranexus, Trevena, Vertex, and Vizuri.

https://doi.org/10.1016/j.semarthrit.2020.10.006
0049-0172/© 2020 Elsevier Inc. All rights reserved.
 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174
suggest that depression and chronic pain conditions involving head/jaw pain and IBS were elevated among
FM patients compared to other conditions in the clinic-based studies. In contrast, anxiety-related disorders
were much less common. Addressing the presence of these comorbid health conditions in clinical trials of
treatments for FM would increase the generalizability and real-world applicability of FM research.
1. Introduction
Fibromyalgia (FM) is a chronic widespread pain condition that over-
laps with multiple comorbid health conditions and contributes to con-
siderable patient distress [1 6]. Understanding the distribution of
comorbid health conditions among patients with FM can guide existing
diagnostic and treatment approaches, support the coordination of care
across medical specialties, and inform the development of recommen-
dations for the design of clinical trials [5,7,8]. For example, the gener-
alizability of clinical trial findings can be influenced by the degree to
which common comorbidities experienced by FM patients are
addressed in study eligibility criteria, data analyses, and interpretation
of results [9]. However, recent reviews cataloging the presence of
comorbid health conditions among FM patient populations have largely
not been systematic [5,7,10 12] or have focused on single disorders,
such as bipolar disorder, depression, and irritable bowel syndrome
(IBS), rather than considering multiple, overlapping comorbidities
[13 17]. Thus, there is a gap in our knowledge regarding the distribu-
tion of different types of comorbid diagnoses among patients diagnosed
with FM. The impetus for this systematic review was to provide an
evaluation of the types of psychiatric and chronic pain comorbid health
conditions commonly reported in clinical studies of FM patients in
order to provide a foundation for the design of clinical trials.
2. Methods
This review was prospectively registered through the PROSPERO
database (July 11, 2019) and designed to examine both FM and Temporo-
mandibular Disorders (TMD) (#CRD42019133249). The preliminary find-
ings associated with the review were presented at an Initiative on
Methods, Measurement, and Pain Assessment in Clinical Trials
(IMMPACT; www.immpact.org) meeting held in July 2019 and were
intended to provide an evidence base for the development of recommen-
dations for the design of clinical trials involving chronic pain conditions
in which central sensitization is considered a prominent mechanism. In
this article, we present the results of the systematic review for chronic
pain and psychiatric comorbidities in patients with FM.
2.1. Literature search strategy
PubMed, PsychInfo, and Embase databases were searched from
database inception (1966, 1967, and 1946, respectively) through
April 27, 2019 (Appendix A). The search strategy was confirmed with
a medical librarian at the University of Rochester School of Medicine
and Dentistry and adapted for the various databases. As noted, the
original literature search string was designed to include both FM and
TMD, as detailed in Appendix A, and the generic search string used
across databases included the following: ((comorbidity or comorbid)
AND (incidence or prevalence or cross-sectional or cohort) AND (psy-
chiatric or mental health disorder or chronic pain)). After identifying
unique citations, two investigators screened and extracted data for
references, and then resolved conflicts through discussion with a
third researcher (BK, MF, or EM).
2.2. Study inclusion criteria
Included studies assessed FM patients diagnosed using established
guidelines from the American College of Rheumatology (ACR) [1 4].
Cohort (prospective or retrospective) and cross-sectional studies were
167
© 2020 Elsevier Inc. All rights reserved.
included for review if they reported original data describing incidence
or prevalence of psychiatric disorders (mood, anxiety, or personality)
or any chronic pain conditions, and were published in English. Confer-
ence abstracts, dissertations, case studies, review papers, and com-
mentaries and editorials were excluded. Studies that assessed
psychiatric disorders were included if diagnoses were made through
in-person assessments by a psychiatrist or other mental health profes-
sional using standardized criteria (e.g., Diagnostic and Statistical Man-
ual of Mental Disorders (DSM) or by interviewers trained to use
standardized assessment tools (e.g., Structured Clinical Interview for
DSM, SCID) [18, 19]. An initial inspection of reviewed papers revealed
that diagnostic details regarding chronic pain conditions were often
described in less detail compared to psychiatric studies. Thus, to be as
inclusive as possible, chronic pain studies were included for review if
the conditions had lasted longer than three months and were either
self-reported, diagnosed by a clinician, and/or if chronicity was inher-
ent to the definition or diagnosis of the disorder [20,21].
2.3. Data extraction
Data extraction forms were developed through an iterative pro-
cess among three reviewers (BK, MF, EM) after pilot data extraction
across five eligible studies. Data captured in extraction forms
included general study information, characteristics of the study pop-
ulation, criteria used to define FM, case definition used for the comor-
bidity, methodological information, and prevalence (Appendix B).
Current and lifetime prevalence estimates were defined as the pro-
portion of FM patients who had been diagnosed with psychiatric dis-
order(s) and/or chronic pain conditions.
2.4. Study quality assessments
The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for
Prevalence Studies was used to evaluate the quality/risk of bias of the
studies included for review and modified slightly to address the
unique attributes of the present review (Appendix C) [22]. Data
extraction using the tool resulted in 16 discrepancies (4.9%) among
reviewers and all were resolved by consensus (BK, MF, EM, or IB).The
final quality assessment tool included seven items and a final total
sum score and a ratio score (sum/total possible) were calculated for
each study, as described in Appendix C. Instructions for the JBI Check-
list do not provide guidance on whether particular scores are indica-
tive of low or high quality [22]. Ratings on this scale are summarized
at the beginning of the Results section without using the qualifiers of
‘high’ or ‘low’.
2.5. Data synthesis
Data were summarized as weighted current and lifetime preva-
lence estimates. If there were not two or more studies to calculate a
weighted prevalence rate, then unweighted prevalence estimates
were reported and are also presented in Figs. 2, 3, and 4. For each
figure, an individual bar represents an unweighted, current, and/or
lifetime prevalence estimate (%) from a single dataset, with the num-
ber of cases associated with each estimate listed to the right of the
bar. In addition, given the wide range of sample sizes across studies,
prevalence estimates weighted by sample size were calculated when
two or more prevalence rates were available for a particular comor-
bid outcome. Weighted prevalence rates were calculated by taking
168 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174
each unweighted prevalence for a given index disorder and comor-
bidity and multiplying it by the total sample size for the associated
study. These weighted values were then summed and divided by the
sum of sample sizes to calculate the weighted average prevalence
rate across studies.
3. Results
3.1. Overview of studies
A total of 683 articles were reviewed for inclusion at the title
and abstract level, of which 514 were deemed ineligible (Fig. 1).
The remaining 169 articles were reviewed at the full text level of
which 138 were primarily excluded for the following reasons
Fig. 1. PRISMA Flow Diagram.
Overview of systematic review results and final study count.
(from most to least common): index disorder diagnosis was not
based on standardized diagnostic criteria (n = 50), psychiatric
outcomes were not based on standardized diagnostic criteria
(n = 48), study did not report prevalence or incidence data
(n = 18), chronic pain and/or psychiatric comorbidities were not
assessed (n = 10), index disorder was TMD, not FM (n = 7) and
article not published in English (n = 2). In addition, three publica-
tions were excluded [23 25] for review because they had over-
lapping data or results with other studies [26 28]. Thirty-one
publications were included for review representing 32 unique
data sets (one publication included two data sets) [29]. Reviewer
extractions across all included studies yielded 184 discrepancies
(4.2% of total extractions) and all were resolved by consensus
among the reviewers (BK, MF, EM, or IB).
 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174 169

All studies were cross-sectional, clinic-based studies reporting
prevalence data and published between 1992 and 2018
[27 43,59 72] (median year of publication = 2010; Appendices D
and E). None of the studies that met inclusion criteria included inci-
dence data. Sample sizes ranged from 22 to 509 (median = 94) and
female participants comprised 80% or more of the each study sample
with the exception of one study [28]. As represented in Appendix D,
all psychiatric diagnoses were based on the DSM-IV with the excep-
tion of six studies that utilized the DSM-III [30 33], Version 2 of The
Schedules for Clinical Assessment in Neuropsychiatry (SCAN) by psy-
chiatrist [34], or the Mini-International Neuropsychiatric Interview
[35]. Chronic pain diagnoses were determined by means of clinical
interview, expert consultation, and/or review of medical records for
most studies. Of these, four studies reported the specific criteria used
to establish a chronic pain diagnosis (in parentheses): the Interna-
tional Headache Society criteria (various types of headache including
migraine), Criteria of Thompson and Associates (IBS), Rome I and
Rome II symptom questionnaires (IBS), and the Research Diagnostic
Criteria (TMD) [36 39]. Specific details on how a chronic pain diag-
nosis was confirmed were not provided in four studies [29,40 42].
The median study quality ratings across all included data sets, repre-
sented in Appendix E, were four out of seven total points with an
overall ratio score of 0.57.
Prevalence data for chronic pain and psychiatric comorbidities
among individuals diagnosed with FM are presented in Figs. 2 4 and
discussed in greater detail below. In some instances, current

Fig. 2. Prevalence of Anxiety Disorders Among Individuals with Fibromyalgia.

Each bar represents the prevalence (%) for 1 study/publication, and values at the end of bars represent patient counts associated with each percent prevalence estimate. Some
publications assessed multiple comorbidities within the same study design and therefore were represented across more than one bar. Abbreviations: Generalized Anxiety Disorder
(GAD); Obsessive Compulsive Disorder (OCD); Posttraumatic Stress Disorder (PTSD). Bars are color-coded as follows: Red anxiety/GAD; Orange PTSD; Yellow Panic disorder;
Green -OCD; Purple Phobic disorders.
170 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174

Fig. 3. Prevalence of Mood Disorders Among Individuals with Fibromyalgia.

Each bar represents the prevalence (%) for 1 study/publication, and values at the end of bars represent patient counts associated with each percent prevalence estimate. Some
publications assessed multiple comorbidities within the same study design and therefore were represented across more than one bar. Abbreviation: Major Depressive Disorder
(MDD). Bars are color-coded in variations of blue to represent different types of mood disorder classifications.

prevalence estimates are larger than lifetime prevalence estimates for
the same outcome/comorbid health condition given that estimates
are collapsed across different studies and participant populations,
resulting in greater current prevalence estimates in some cases.
3.2. Psychiatric disorders
The majority of the studies reviewed [21] examined psychiatric
disorders among FM patients (Appendices D and E). Studies were
conducted across seven countries with the majority in Italy [8] and
the United States (US) [6], and sample sizes ranged from 33 to 509.
Sixteen studies examined anxiety disorders and 14 examined mood
disorders (Figs. 2 and 3; top and bottom panels represent unweighted
current and lifetime prevalence, respectively). Only two studies
examined personality disorders (labeled as ‘general’ or borderline)
[32,43] (Table 1). As presented in Table 1, weighted prevalence rates
were higher for mood disorders relative to anxiety disorders. For
example, current prevalence for depression (not otherwise specified)
and major depressive disorder (MDD) were 43.0% and 32.0%, respec-
tively, and lifetime prevalence for the same disorders were even
 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174 171

Fig. 4. Prevalence of Chronic Pain Comorbidities Among Individuals with Fibromyalgia.

Each bar represents the prevalence (%) for 1 study/publication, and values at the end of bars represent patient counts associated with each percent prevalence estimate. Some
publications assessed multiple comorbidities within the same study design and therefore were represented across more than one bar. Abbreviations: Irritable Bowel Syndrome
(IBS); Osteoarthritis (OA); Rheumatoid Arthritis (RA); Temporomandibular Disorders (TMD). Bars are color-coded as follows: Yellow stomach/pelvic/genital pain; Gray back
pain; Blue FM or TMD; Red Headache; Green IBS; Purple Arthritis; Orange Myofascial syndrome

higher at 63.0% and 52.3%, respectively. In contrast, current preva-
lence for anxiety (not otherwise specified) and generalized anxiety
disorder (GAD) were slightly lower at 30% and 8.4%, respectively. Life-
time prevalence of GAD was only 9.1% (lifetime prevalence rates for
anxiety, not otherwise specified, were not available). Other notable
findings included relatively high lifetime prevalence rates of bipolar
disorder (26.2%) and panic disorder (33.0%), both of which were the
most commonly assessed psychiatric conditions across all categories.
Lastly, current (39.1%) and lifetime (16.1%) weighted prevalence rates
for PTSD, and current personality disorder (19.3%), were lower com-
pared to depression/MDD. Rates of obsessive-compulsive disorder
(OCD) (current, 2%; and lifetime: 4.3%) and phobic disorders (e.g.,
social phobia: current, 17.7%, and lifetime, 14.0%) were relatively low
compared to other psychiatric diagnoses. Dysthymic disorder was
the only psychiatric disorder that was evaluated in a single study and
not represented among weighted prevalence estimates (lifetime
prevalence: 53%; Fig. 3, bottom panel).
3.2. Chronic pain conditions
Thirteen studies examined 10 chronic pain comorbidities among
people diagnosed with FM (Fig. 4; top and bottom panels represent
unweighted current and lifetime prevalence, respectively). The stud-
ies were conducted across 5 countries (from most to least frequent):
United States [6], Spain [3], Italy [2], Turkey [2], and Canada [1]. Pub-
lication years ranged from 1992-2018, and samples ranged in size
from 22 to 536. As presented in Table 1, current weighted prevalence
estimates among cases with FM were high for both myofascial syn-
drome (76.0%) and IBS (45.0%). Interestingly, weighted prevalence for
current chronic migraine headache was relatively low compared to
172 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174

other chronic pain comorbidities (10.0%), while weighted prevalence
across studies for lifetime migraine headaches was relatively high
(56%; note that these current and lifetime prevalence estimates were
not derived from the same studies or patient populations). Overall,
lifetime prevalence for a variety of chronic pain conditions (head-
ache/chronic tension-type, IBS, lower back pain, and TMD) was high
and ranged from 39% to 57% across patient populations. Pain condi-
tions that were assessed in 1 study each tended to provide lower esti-
mates compared to the weighted prevalence found in Table 1. These
data included the current prevalence estimates for analgesic overuse
headache (6%), trauma-related headache (4%), tension-type headache
(18%), combined migraine/tension headache (16%), pelvic pain (16%),
and rheumatoid arthritis (5.9%), as well as the following lifetime
prevalence estimates for osteoarthritis (40%), pelvic pain (18%), rheu-
matoid arthritis (12.1%), and interstitial cystitis (8%) (all data repre-
sented in Fig. 4).
4. Discussion
This systematic review identified 32 unique data sets across 31
published studies that included prevalence estimates for psychiatric
and/or chronic pain comorbidities among individuals diagnosed with
FM. All of the studies included for review were conducted in health-
care clinic settings and the majority addressed psychiatric comorbid-
ities (21 studies). None of the reviewed studies reported on the
incidence of chronic pain, which could be explained by the tendency
of many FM-related symptoms to alter in intensity, remit, or recur,
making the precise timing of the condition difficult to determine
[44]. The most prevalent comorbidity across all studies reviewed was
depression/MDD, with over half of the patients having this diagnosis
in their lifetime in the studies reviewed (weighted prevalence
ranging from 52% to 63%). This finding confirms the results of a recent
meta-analysis that focused only on MDD [15]. Other psychiatric dis-
orders were also quite prevalent across studies, with nearly one-third
of FM patients examined having current or lifetime bipolar disorder,
panic disorder, anxiety disorder (not otherwise specified), or PTSD.
These values are striking given that current rates of depression and
anxiety in the general population are estimated to range from 3 to
10% [45 47]. Less prevalent psychiatric disorders across studies
included GAD, OCD, and specific phobias (agoraphobia, social pho-
bia).
Weighted- current and lifetime prevalence rates for several
chronic pain comorbidities were also high and ranged between 39%
and 76% (i.e., chronic tension-type or migraine headache, IBS, lower
back pain, myofascial pain syndrome, and TMD) (Table 1). By compar-
ison, general population-based estimates for these conditions are
much lower and range from about 5% to 11% for lifetime prevalence
[48 50]. These high rates of chronic pain comorbidities reported
across studies reviewed provides some support for the idea that FM
has attributes of centrally mediated pain [51]. Despite the connection
between FM and pain, the present review found that chronic pain
comorbidities were less commonly assessed in studies of FM relative
to psychiatric comorbidities. This, in turn, made it impossible to pro-
vide collapsed, weighted prevalence estimates across studies for sev-
eral pain conditions because they were each only represented in a
single study (e.g., osteoarthritis, rheumatoid arthritis).
There are several key limitations of the present review that should
be noted. First, the reliability of the prevalence estimates reported are
limited by the small sample sizes (N < 100) and convenience sam-
pling associated with clinic-based studies. For example, the majority
of studies were primarily comprised of women (>80%) and this could
be due to a reliance on ACR 1990 criteria for the classification of FM,

Table 1
Prevalence Estimates Weighted by Sample Size.

Comorbidity Prevalence Type Number of studies Weighted Prevalence Rate

FM Psychiatric - Anxiety Disorders Anxiety* Current 6 30.0%

GAD Lifetime 3 9.10%
GAD Current 5 8.40%
OCD Lifetime 4 4.30%
OCD Current 3 2.0%
Panic Disorder Lifetime 10 33.0%
Panic Disorder Current 9 11.6%
Phobia* Current 2 19.6%
Phobia (Agoraphobia) Lifetime 3 12.0%
Phobia (Social) Lifetime 3 14.0%
Phobia (Social) Current 4 17.7%
PTSD Lifetime 2 16.1%
PTSD Current 3 39.1%
FM Psychiatric - Mood Disorders Bipolar Disorder Lifetime 7 26.2%
Bipolar Disorder Current 4 4.2%
Depression* Lifetime 3 63.0%
Depression* Current 3 43.0%
Dysthymic Disorder Current 2 3.9%
MDD Lifetime 7 52.3%
MDD Current 7 32.0%
Mood disorder* Current 6 30.4%
FM Psychiatric Personality Disorder Personality Disorder Current 2 19.3%
FM Chronic Pain Headache (chronic tension-type) Lifetime 3 48.0%
Headache (migraine) Lifetime 2 56.0%
Headache (migraine) Current 3 10.0%
IBS Lifetime 5 44.0%
IBS Current 6 45.0%
Lower back pain Lifetime 2 39.0%
Myofascial Syndrome Current 2 76.0%
TMD Lifetime 3 57.0%
*Specific type of comorbidity not reported. Note that post-traumatic stress disorder (PTSD) was considered an anxiety disorder in the current review given
that most of the studies reviewed were conducted prior to its new designation as a ‘Trauma and Stressor-Related Disorder’ separate from anxiety disorders.
One study (37) reported two types of IBS diagnostic criteria (Rome I and Rome II); scores for the more recently endorsed Rome II criteria were analyzed in
the present review.
 B.A. Kleykamp et al. / Seminars in Arthritis and Rheumatism 51 (2021) 166 174
which tends to under diagnose the condition in male populations
[52 54]. The majority of FM studies in our review included ACR 1990
criteria rather than more recent diagnostic criteria, which could
explain why more females were represented across studies. An addi-
tional limitation of the present review is the reality that prevalence
estimates are likely to vary across the clinic sites and patient samples,
and these differences can contribute to variation in prevalence esti-
mates across studies (e.g., Figures 2 through 4) [55]. Lastly, each of
the conditions evaluated in the present review exist on a spectrum of
symptoms and signs that likely vary between patients, and this vari-
ance is not fully captured by the dichotomous diagnostic categories
we utilized in our review.
4.1. Conclusions
The present review confirms that FM patients have elevated rates
of specific psychiatric, especially for depression/MDD. There were far
fewer studies that examined chronic pain comorbidities among FM
patients, but when evaluated, rates tended to be highest and most
frequently reported for migraine headaches and IBS. These findings
highlight the importance of accounting for the comorbidity status of
FM patients enrolled in clinical trials including the representation of
comorbidities within inclusion and exclusion criteria. In addition,
comorbid conditions likely influence treatment response, tolerability,
and the safety of interventions and these potential effects should be
examined in study data analyses and interpretation of results. The
results of the review also highlight knowledge gaps in the literature
regarding comorbidities among FM patients including a lack of inci-
dence data for the comorbid conditions a wide range of prevalence
estimates across published studies. Future research that can link clin-
ical data, such as those presented in the present review, with admin-
istrative claims data might allow for a more complete evaluation of
multimorbidity among FM patients [56 58]. Overall, this review
adds to a growing body of work confirming the inordinate disease
burden shared among individuals diagnosed with FM and the need
to account for these comorbidities in clinical trials of FM to ensure
the generalizability and real-world applicability of study findings.
Acknowledgements
The authors wish to thank Linda Hasman at the University of
Rochester School of Medicine and Dentistry for her assistance in
building the search strategy.
Supplementary materials
Supplementary material associated with this article can be found,
in the online version, at doi:10.1016/j.semarthrit.2020.10.006.
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