Special review article
A meta-analysis investigating the prevalence and moderators of migraines among people with bipolar disorder

https://doi.org/10.1016/j.jad.2015.02.032Get rights and content

Abstract

Background

Uncertainty exists regarding the prevalence and moderators of migraine comorbidity among people with bipolar disorder (BD). We conducted a meta-analysis and meta-regression to investigate the prevalence and moderators of migraine among people with BD.

Method

Two authors independently searched major electronic databases from inception till 02/2015. Articles were included that reported the prevalence of migraine in people with BD with or without a control group. A random effects meta-analysis and exploratory meta-regression were conducted.

Results

Fourteen studies were included encompassing 3976 individuals with BD (mean age 35.5 years, SD 7.6, 29% male). The overall pooled prevalence of migraine was 34.8% (95% CI=25.54–44.69). The prevalence of migraine was higher among people with BD-II (54.17%, 95% CI=31.52–75.95, n=742) compared to BD-I (32.7%, 95% CI=18.16–49.19, n=2138, z=3.97, p<0.0001). The prevalence of migraine was 33.9% (95% CI=26.02–42.44), 39.5% (95% CI=18.81–62.39) and 47.11% (95% CI=22.24–72.77) in North America, Europe and South America respectively. The prevalence of migraine was higher when classified according to recognized criteria at 47.91% (95% CI=32.51–63.5) compared to non-recognized criteria (20.0%, 95% CI=12.44–29.06, z=−8.40, p<0.0001). Meta regression suggests mean age may be a potential moderator.

Conclusion

Migraine is common and burdensome among people with BD. People with BD-II appear to be particularly affected. Nonetheless, future research is required to better understand these relationships, with a special emphasis toward the course specifiers of comorbid migraine cases of either BD-I vs. BD-II.

Introduction

Migraine is one the oldest ailments known to mankind (Mandal, 2014). Some of the earliest cases of painful headaches were recorded by the ancient Egyptians and date back as far as 1200 B.C. (Karenberg and Leitz, 2001). Much later, in around 400 B.C., Hippocrates referred to the visual disturbances that can precede a migraine such as flashing lights or blurred vision (“aura”) (Breitenfeld et al., 2014). However, the credit for migraine “discovery” was given to Aretaeus of Cappadocia who described in the second century the one sided or unilateral headaches that are typical of migraines as well as the associated vomiting and the windows of time between migraines that are symptom free (Koehler and van de Wiel, 2001). The word “migraine” itself derived from the Latin word “hemicrania” meaning “half” (hemi) “skull” (crania). This term was first used by Galenus of Pergamon to describe the pain felt across one side of the head during a migraine (Isler, 1992). Yet the documentation of “migraine” features, already documented even in course of “mood disturbances”, was not unique to Western cultures, as recorded by the Chinese surgeon Hua Tuo (late Han Dynasty, second century A.D.) who was the first to successfully use acupuncture needles to relieve the “recurrent” migraines complained by the “irritable, moody” and “tyrannical” founder of his kingdom (Fu, 2002). Similarly, the Islamic philospher Avicenna described migraine in his textbook on medicine “El Qanoon fel teb”, a treatise which is also nowadays considered one of the earliest texts on “melancholia and mania” (Omrani et al., 2012), documenting how eating, drinking, sounds and light all worsened the pain felt during a migraine (Abokrysha, 2009), a report that should nowadays appear clinically intriguing also considering that “hyperesthesia” (sensory over-sensitivity) has been recently linked even to anxious, irritable and mood disturbances (Sylvia et al., 2014). Avicenna described how these patients tended to rest alone in a dark room until the attack passed, but it was Abu Bakr Mohamed Ibn Zakariya Râzi who pointed to an association between migraine and hormones when he referred to how such headaches would occur during menopause, after childbirth or during dysmenorrhea (Mandal, 2014), all conditions that would nowadays potentially linked to the broad definition of bipolar spectrum when leading to “maternity blues”, “post-partum depression” or menstrual disturbances (Akiskal and Mallya, 1987, Di Florio et al., 2013, Fornaro and Perugi, 2010). Yet, it was not until the publication of the results from large studies in carried in Zurich (Merikangas et al., 1990) and Detroit (Breslau et al., 1994) that migraine was systematically documented to be more frequent in mood disorder patients, including bipolar disorder (BD) cases, than in controls.

According to the International Classification of Headache Disorders, 2nd edition (ICHD-2), migraine refers to different phenotypes having in common a low threshold to the development of headache among migraineurs, usually being characterized for a recurring pattern, frequent free-interval, and usually provoked by stereotyped triggers (Headache Classification Subcommittee of the International Headache Society, 2004). Nonetheless, while a conclusive definition of migraine remains elusive, especially due to the heterogeneity of some of the frequently associated neurological and psychiatric comorbidities, a three-fold increase in migraine prevalence in patients with BD has been ascertained (Merikangas et al., 1993), as outlined by a recent systematic review about the prevalence of migraine comorbidity among people with BD (Fornaro et al., 2015). This latter systematic review, first of its kind at writing time, whilst helpful, updated and informative, did not undertake a meta-analysis, nor was there any attempt to stratify the results according to diagnosis (BD-I vs. BD-II), setting or location. Information about how the prevalence of migraine may be influenced according to the classification of BD, geographical location and the criteria used to define a migraine are nonetheless clinically relevant, and conducting meta-analyses offers the potential to provide the most accurate effect size of an actual phenomenon and enable researchers to make wider conclusions than considering individual studies in isolation. Given the burden of migraine among people with BD, there is a need to better understand the prevalence and moderators of migraine. Therefore, to the best of our knowledge, we set out to conduct the first meta-analysis to investigate the prevalence and moderators of migraine comorbidity among people with BD.

Section snippets

Material and methods

The present meta-analysis adhered to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines (Stroup et al., 2000). The current paper followed the inclusion and exclusion criteria already adopted for our recent Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) systematic review (Fornaro et al., 2015), but extended the inclusion criteria to account also for contributes indexed in PubMed since inception. In addition, searches were updated on all

Study selection

The search in PubMed generated 134 papers, and 595 results in Scopus. Thirteen additional results were obtained through search either in Cochrane (n=7), PsycLit, PsycInfo or reference textbooks/manual search. Refer to Fig. 1 for a synthetic flow chart of the multi-step selection procedure which allowed to retain 14 final original studies accounted in our quantitative analysis.

Included study and participant characteristics

With the sole exception of three retrospective studies (Holland et al., 2011, Munoli et al., 2014, Saunders et al., 2014

Discussion

The current meta-analysis is to our knowledge a first and established that overall approximately one third of people with BD are affected by comorbid migraine (34.8%, 955% CI=25.54–44.69, n=3976). Of particular interest, we have established that higher prevalence of migraine exists among people with BD-II (54%) vs. those with BD-I (32.7%, p<0.0001). Interestingly, we also established for the first time that the prevalence of migraine is substantially higher in studies utilizing recognized

Role of funding source

The authors have no funding source to disclose in conjunction with the present work.

Conflict of interest

The authors have no conflict of interest, neither financial support to disclose in conjunction with the present work.

Acknowledgments

None to state.

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