Co-occurring pain syndromes.

1. Brief Communication
Frequency of Migraine Headaches in Patients
With Fibromyalgia
Brinder Vij, MD, FACP; Mary O. Whipple, BSN, RN, CCRP; Stewart J. Tepper, MD;
Arya B. Mohabbat, MD; Mark Stillman, MD; Ann Vincent, MD
Objective.—The purpose of this study was to evaluate the frequency of migraine headache in a large cohort of patients with
fibromyalgia using a brief migraine headache-screening tool.
Background.—Several studies report a high prevalence of fibromyalgia among patients with migraine headaches, but there
is a dearth of research evaluating the frequency of migraine headaches in patients with fibromyalgia, despite clinical observa-
tions suggesting that migraine headaches are common in patients with fibromyalgia.
Design and Methods.—This was a cross-sectional survey study. Patients (N = 3717) with a previous diagnosis of
fibromyalgia who were members of the Mayo Clinic Fibromyalgia Registry were contacted by electronic survey and asked to
complete a brief demographic and medical history questionnaire and the validated ID-Migraine screener.
Results.—A total of 1730 patients (46.5%) completed the electronic survey. The majority of participants were white
(97.2%), female (92.5%), with a mean age of 56.2 (±13.1) years. Of the respondents, 966 (55.8%) met criteria for migraine
headaches. Hypertension (309 [32.3%] vs 294 [40.1%], P = .004), asthma (312 [32.5%] vs 189 [25.9%], P = .011), irritable bowel
syndrome (520 [54.6%] vs 348 [47.6], P = .017), chronic fatigue syndrome (486 [50.7%] vs 271 [37.1], P < .0001), depression (634
[66.5%] vs 413 [56.7%], P = .0002), anxiety (415 [43.5%] vs 252 [34.7%], P = .0011), and post-traumatic stress disorder (172
[18.0%] vs 96 [13.2%], P = .006) were all significantly more common in those who met criteria for migraine headaches than
those who did not.
Conclusion.—The results of this study suggest that migraine headaches are common in patients with fibromyalgia.
Clinicians who care for either population must be aware that these conditions commonly overlap and can significantly increase
a patient’s cumulative disease burden.
Key words: migraine, headache, fibromyalgia, ID-Migraine, chronic pain, central sensitization
(Headache 2015;55:860-865)
From the Headache Center, Neurology Institute, Cleveland Clinic, Cleveland, OH, USA (B. Vij, S.J. Tepper, and M. Stillman);
Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA (M.O. Whipple, A.B. Mohabbat, and A. Vincent).
Address all correspondence to B. Vij, Headache Center, Neurology Institute, Cleveland Clinic, C-21, 9500 Euclid Avenue, Cleve-
land, OH 44195, USA.
Accepted for publication April 12, 2015.
Conflict of Interest: Drs. Vij, Mohabbat, Stillman, and Vincent, and Ms. Whipple have no conflicts of interest to disclose. Dr. Tepper
received grants/research support from Allergan, Amgen, ATI, Avanir, BristolMyerSquibb, ElectroCore, GSK, Labrys, MAP/
Allergan, Merck, NuPathe, Optinose, and Zogenix. These grants do not go to him personally and do not count toward his salary at
Cleveland Clinic. All amounts received are <$10,000/year per Cleveland Clinic Policy and are listed on the Cleveland Clinic Web
site. In the last 12 months, he has served as a consultant for Allergan, Amgen, ATI, Avanir, Civitas, Depomed, Dr. Reddy, Impax,
Labrys, MAP, Nautilus, NuPathe, Pfizer, Teva, and Zogenix. In the last 12 months, he has served on the Speakers Bureau for
Allergan, Depomed, and Zogenix. In the last 12 months, he served on Advisory Boards for Allergan, Amgen, ATI, Avanir,
Depomed, Labrys, MAP, Nautilus, NuPathe, Teva, and Zogenix. He receives royalties for books published by Peoples Medical
Publishing House of Peking, University of Mississippi Press, and Springer. He has stock options in ATI.
ISSN 0017-8748
doi: 10.1111/head.12590
Published by Wiley Periodicals, Inc.
Headache
© 2015 American Headache Society
860

2. Headache and migraine are common and costly
public health problems.1
Previous research has esti-
mated that worldwide, 46% of the adult population
has an active headache disorder, 42% have tension-
type headache, and 11% have migraine.2,3
Women are
two to three times more likely than men to experi-
ence migraine headache, and women who experience
migraine headache have significantly greater impair-
ment and health-care utilization than men with
migraine.4
Several studies reported that a high propor-
tion (20–31%) of patients with migraine have
fibromyalgia.5-8
In a study by Ifergane et al, the
researchers found that in a sample of 92 patients with
migraine headaches, 22.2% of the females met the
criteria for fibromyalgia.6
In another large study,
researchers found 24.3% of patients with migraine
met criteria for fibromyalgia.8
Despite a few studies
using samples of patients with migraines, research
on the frequency of migraine in patients with
fibromyalgia is minimal, despite clinical observations
suggesting that migraine is common in patients with
fibromyalgia. In one small study comparing patients
with fibromyalgia with those with arthritis and
healthy controls, self-report of migraine was signifi-
cantly higher in patients with fibromyalgia (72%)
than in patients with arthritis (43%) or healthy con-
trols (13%).9
The explanation for the high degree of
comorbidity between migraine and fibromyalgia is
unclear; altered pain control mechanisms and neuro-
endocrine dysfunction associated with both disorders
may be responsible.10,11
Research also suggests that the presence of both
headache and fibromyalgia have a substantial impact
on disease burden.6,12
Given this, and the purported
high degree of comorbidity between fibromyalgia
and migraine, assessment of migraine in patients with
fibromyalgia is paramount. The purpose of this study
was to evaluate the frequency of migraine headache
in a large cohort of patients with fibromyalgia using a
brief, three-item migraine headache-screening tool.
METHODS
In order to evaluate the extent of the problem of
migraine headaches in patients with fibromyalgia,
patients with a previous diagnosis of fibromyalgia
were contacted by electronic survey. This study was
reviewed and approved by the Mayo Clinic and
Cleveland Clinic Institutional Review Boards.
Participants.—Study participants were identified
from the Mayo Clinic Fibromyalgia Registry.13
This is
a national fibromyalgia registry consisting of over
6000 patients who have been seen at Mayo Clinic
between January 1, 2000 and December 31, 2013 and
have a diagnosis or history of fibromyalgia docu-
mented in their medical record.At the time of enroll-
ment into the registry, medical record review was
conducted to confirm a diagnosis of fibromyalgia.
All participants also completed a basic demographic
questionnaire (age, sex, height, weight) and the
Fibromyalgia Research Survey14
at the time of enroll-
ment into the registry.
Procedure.—An electronic survey was sent
between August 2014 and October 2014 using
Research Electronic Data Capture (REDCap;
Vanderbilt University, Nashville, TN, USA) to all
patients in the fibromyalgia registry who agreed to be
contacted for future research, and provided an e-mail
address by which to contact them (n = 4421). Patients
who did not respond to the initial request were sent
up to three reminders at weekly intervals.
Measures.—Participants completed a brief demo-
graphic and medical history questionnaire and the
validated ID-Migraine screener.15,16
Demographic and Medical History
Questionnaire.—The demographic questionnaire
included questions regarding race, ethnicity, educa-
tion, marital status, and employment status. The
medical history questionnaire asked participants to
indicate whether they had a current or past diagnosis
of hypertension, coronary artery disease, myocardial
infarction, mitral valve prolapse, epilepsy, stroke,
asthma, irritable bowel syndrome, gastrointestinal
disorder, glaucoma, Raynaud’s phenomenon, chronic
fatigue syndrome, depression, anxiety disorder,
bipolar disorder, and post-traumatic stress disorder.
ID-Migraine Screener.—The three-item ID-
Migraine screener is a valid and reliable screening
instrument for migraine headache.15,16
The three items
assess the presence or absence of associated nausea
and photosensitivity, as well as headache disability or
impact on work, study, home, recreational activities,
Headache 861

3. nausea, and photosensitivity. It has a sensitivity of
0.81 and specificity of 0.75, and a positive predictive
value 0.93 for the diagnosis of migraine.
Statistical Analyses.—Descriptive statistics (mean,
standard deviation [SD], and percent) were used to
characterize the sample.Chi-square tests were used to
compare the presence of medical and psychiatric
comorbidities between those who did and those who
did not meet the criteria for migraine headache.
Analyses were conducted with JMP Statistical Soft-
ware (Version 10, SAS Institute Inc, Cary, NC, USA).
P values < .05 were considered significant.
RESULTS
A total of 4421 patients in the Mayo Clinic
Fibromyalgia Registry13
who had previously agreed to
be contacted regarding fibromyalgia research were
sent the electronic survey.Of those,704 were returned
not deliverable;thus,3717 patients were contacted.Of
the 3717 contacted,137 declined participation,leaving
a total of 1730 (46.5%) completed surveys.
Descriptive characteristics of the surveyed cohort
are summarized in Table 1. The majority of partici-
pants were white (97.2%) and non-Hispanic (98.1%).
Ninety-two percent were female, with a mean age of
56.2 (±13.1) years.
In order to determine if those who responded to
the survey may differ from those who did not, demo-
graphic characteristics (age, race, and gender) were
compared between respondents and nonrespondents.
There were no differences between the two groups in
regard to gender (92.5% of respondents and 91.2% of
nonrespondents were female, P = .11) or race (97.2%
of respondents and 96.9% of nonrespondents were
non-Hispanic white, P = .30), but nonrespondents
were older than respondents (mean age of 57.5 [SD
13.1] years compared with a mean age of the respon-
dent group of 56.2 [SD 13.1] years, P = .0009).
Of the respondents, 966 (55.8%) met the criteria
for migraine headaches (at least two of the three
ID-Migraine symptoms – sensitivity to light, nausea,
and effect of headache on activity).A number of self-
reported medical and psychiatric comorbidities were
significantly more common in patients who met crite-
ria for migraine than those who did not, including
hypertension (P = .004), asthma (P = .011), irritable
bowel syndrome (P = .017), chronic fatigue syndrome
(P < .0001), depression (P = .0002), anxiety (P =
.0011), and post-traumatic stress disorder (P = .006)
(summarized in Table 2).
DISCUSSION
This cross-sectional study demonstrates that
migraine headache, when defined using the ID-
Migraine screening questionnaire, is very common
among patients with fibromyalgia. Additionally, of
significant statistical and clinical relevance, patients
with both migraine and fibromyalgia report a greater
number of medical and psychiatric comorbidities
than those with fibromyalgia alone. While previous
Table 1.—Sample Characteristics
Variable
Mean (SD)
or n [%]
Age 56.2 (13.1)
Gender
Female 1726 [92.5]
Male 139 [7.5]
Race
White 1681 [97.2]
Other 49 [2.8]
Ethnicity
Hispanic 33 [1.9]
Non-Hispanic 1676 [98.1]
Marital Status
Married 1228 [71.5]
Divorced 188 [10.9]
Separated 16 [0.9]
Single 152 [8.9]
Widowed 66 [3.8]
Committed relationship 63 [3.7]
Other 4 [0.2]
Education
Eight grade or less 3 [0.2]
Some high school but did not graduate 8 [0.5]
High school diploma 227 [13.1]
Some college/associate degree 684 [39.6]
Four-year college graduate 358 [20.7]
Postgraduate 447 [25.9]
Employment
Employed 523 [30.4]
Unemployed 75 [4.4]
Work disabled 330 [19.2]
Student 22 [1.3]
Retired 496 [28.8]
Self-employed 112 [6.5]
Full-time homemaker 106 [6.2]
Other 59 [3.4]
862 June 2015

4. studies demonstrated a high frequency of fibromyal-
gia in patients with migraine, this study is one of the
first to estimate the frequency of migraine in a well-
characterized sample of patients with fibromyalgia.
The high concomitance of fibromyalgia and
migraine suggests that these pain disorders may
share some degree of common pathophysiology. In
fibromyalgia, as in migraine headache, the underlying
etiology appears to be multifactorial. Several of these
factors include alterations in neuroendocrine func-
tion, vascular changes, immunomodulation, neuronal
plasticity, central and peripheral modulation of noci-
ceptive neurons, hormonal influences, and neuro-
chemical alterations.17,18
Separate studies utilizing
functional magnetic resonance imaging in migraine
and fibromyalgia have demonstrated a similar pattern
of cortical hyperactivation to experimentally induced
painful stimuli.19,20
Although this shared pattern of
activation requires further exploration, both disor-
ders seem to share some component of central
sensitization.
A few studies have suggested a high prevalence
of various medical and psychiatric comorbidities
in patients with fibromyalgia.21-26
The comorbidities
include: irritable bowel syndrome, chronic fatigue
syndrome, rheumatoid arthritis, systemic lupus ery-
thematosus, osteoarthritis, sleep disorders, hyperten-
sion, type 2 diabetes, depression, and anxiety. Our
results are similar to those previously reported,
although the explanation for this high degree of
comorbidity is currently unclear.
Given the high comorbid rate of migraine head-
ache and fibromyalgia, further research is needed to
evaluate how each condition influences the other.
Further studies should focus on the impact that
migraine headache may have on other fibromyalgia
symptoms, the cumulative symptomatic burden for
the patient who has both disorders, and investigate
possible overlapping treatment strategies to help
address both conditions concomitantly. From a clini-
cal perspective, our findings highlight the need for
proper evaluation and management of both migraine
headache and fibromyalgia (when either condition
is present) in order to provide symptomatic improve-
ment.27
Clinicians who frequently interact with
patients with either fibromyalgia or migraine must be
cognizant of the coexistence of these two conditions.
Strengths of our study include the large sample
size and utilization of validated and reliable screening
and assessment tools. Nevertheless, our study has
several limitations. First, it is important to consider
participation bias when interpreting our results.There
were differences between those who participated
and those who did not in regard to age. Despite this
Table 2.—Comparison of Frequency of Comorbidities Between Those Fibromyalgia Patients Meeting and Not Meeting Criteria
for Migraine
Variable
Migraine
(N = 966) [%]
No migraine
(N = 764) [%] P value
Missing
N [%]
Epilepsy 25 [2.6] 18 [2.4] .9267 11 [0.6]
Stroke 38 [4.0] 30 [4.1] .3018 17 [1.0]
Hypertension 309 [32.3] 294 [40.1] .0040 18 [1.0]
Mitral valve prolapse 75 [7.9] 80 [11.0[ .0891 29 [1.7]
Coronary artery disease/myocardial infarction 57 [6.0] 46 [6.3] .6224 22 [1.3]
Asthma 312 [32.5] 189 [25.9] .0114 17 [1.0]
Irritable bowel syndrome 520 [54.6] 348 [47.6] .0173 23 [1.3]
Gastrointestinal disorder 404 [42.1] 281 [38.5] .2720 20 [1.2]
Glaucoma 42 [4.4] 41 [5.7] .5083 41 [2.4]
Raynaud’s 169 [17.7] 117 [16.0] .2321 25 [1.4]
Chronic fatigue syndrome 486 [50.7] 271 [37.1] <.0001 19 [1.1]
Depression 634 [66.5] 413 [56.7] .0002 24 [1.4]
Anxiety 415 [43.5] 252 [34.7] .0011 28 [1.6]
Bipolar disorder 41 [4.3] 20 [2.8] .1595 31 [1.8]
Post-traumatic stress disorder 172 [18.0] 96 [13.2] .0057 27 [1.6]
Headache 863

5. statistically significant difference (likely because of
high N), the difference in age (57.5 years vs 56.2
years) between nonresponders and responders is
probably clinically irrelevant. There may be further
differences in regard to symptoms or other character-
istics (eg, education), which limit the generalizability
of our findings. Second, given the electronic, self-
report nature of this survey, it is possible that our
study resulted in a different estimate of the fre-
quency of migraine headache and comorbidities in
fibromyalgia than would have resulted from a clinical
evaluation. Additionally, because we did not include
an assessment of the frequency with which migraine
headaches occur and any associated disability, we are
limited in our ability to assess the impact of comorbid
migraine headaches and fibromyalgia. A third limita-
tion may be that patients who suffer from migraine
may have considered the survey more personally rel-
evant and therefore may have been more willing to
view and complete the survey, thus artificially raising
the comorbidity percentage despite communication
and reminders that all patients with fibromyalgia
were eligible to participate.A fourth limitation is that
given that the magnitude of the gender discrepancy
in fibromyalgia is greater than it is in migraine, our
results are likely not generalizable to all patients with
migraine. Finally, the nonmigraine group is likely not
the ideal comparison group; future studies that
include nonheadache individuals will allow for better
comparisons.
CONCLUSIONS
The results of our study suggest that migraine
headache is common in patients with fibromyalgia.
Clinicians who care for either population must be
aware that these conditions commonly overlap and
can significantly increase a patient’s cumulative
disease burden. As such, it is imperative to screen for
and treat each condition accordingly.
Acknowledgments: Study data were collected and
managed using REDCap electronic data capture tools
hosted at Mayo Clinic. REDCap 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 pack-
ages; and (4) procedures for importing data from external
sources.
STATEMENT OF AUTHORSHIP
Category 1
(a) Conception and Design
Brinder Vij; Mary O. Whipple; Ann Vincent
(b) Acquisition of Data
Brinder Vij; Mary O. Whipple; Ann Vincent
(c) Analysis and Interpretation of Data
Brinder Vij; Mary O. Whipple; Stewart J. Tepper;
Arya B. Mohabbat; Mark Stillman; Ann Vincent
Category 2
(a) Drafting the Manuscript
Brinder Vij; Mary O.Whipple;Arya B. Mohabbat;
Ann Vincent
(b) Revising It for Intellectual Content
Brinder Vij; Mary O. Whipple; Stewart J. Tepper;
Arya B. Mohabbat; Mark Stillman; Ann Vincent
Category 3
(a) Final Approval of the Completed Manuscript
Brinder Vij; Mary O. Whipple; Stewart J. Tepper;
Arya B. Mohabbat; Mark Stillman; Ann Vincent
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