The association between migraine and depression has been described in both clinic and community-based populations. Early studies established a cross-sectional association between the 2 disorders, while subsequent investigations examined the temporal sequence of the association. Persons with migraine were followed-up to determine if they developed depression at increased rates and persons with depression were followed-up to examine the incidence of migraine. To explain an association from migraine to depression, it has been hypothesized that unpredictable attacks of severe pain might lead to anxiety and depression, perhaps through mechanisms akin to those of learned helplessness (noncontingent punishment). Conversely, to explain a link from depression to pain, it has been postulated that headache could be a somatic manifestation of depression or impair the patients’ ability to cope with pain. If the association is bidirectional (if each disorder predisposes to the other), the association may arise from an underlying common vulnerability.
While a cross-sectional association between migraine and major depression has been reported in both clinical and population-based settings, herein we will focus on the studies in unselected populations because these studies support more robust causal inferences. Table 1 summarizes the association between migraine and depression in a number of large scale community studies.
In this table, estimates of the relative risk for the association between migraine and depression range from 2.2 to 4.0. In general, the cross-sectional studies measure strength of association using the Odds Ratio (OR), while most longitudinal studies measure association using the Hazard Ratio (HR).
Merikangas et al studied the association of psychiatric syndromes, including depression, and migraine headache in a prospective epidemiologic cohort of 27- and 28-year-olds in Zurich, Switzerland. In this study, 457 subjects (225 men and 232 women) were interviewed to assess presence of psychiatric syndromes and/or migraine headache. The criteria for classification of headache were based on the IHS criteria, but the diagnoses did not strictly adhere to the guidelines. Standardized psychiatric assessments were used to diagnose the psychiatric syndromes. Migraine was strongly associated with major depression (OR 2.2, 95% CI 1.1 to 4.8). This was the first study to demonstrate a strong association between migraine and major depression in an unselected sample.
Breslau et al conducted a population-based study of people 25 to 55 years of age with migraine or other severe headaches to examine the relationship between migraine and major depression. This study used Cox proportional hazards models to estimate the risk for the first occurrence of migraine associated with prior major depression and the risk for depression associated with prior migraine. Similar Cox proportional hazards models were used to estimate the risk for the first occurrence of severe headache associated with major depression and vice versa. In this study, migraine was strongly associated with major depression (Sex-adjusted OR 3.5, 95% CI 2.6 to 4.6). The association was higher in people with migraine with aura (Sex-adjusted OR 4.9, 95% CI 3.3 to 7.2) than in people with migraine without aura (Sex-adjusted OR 3.0, 95% CI 2.2 to 4.1). Interestingly, the association was also present for severe headache (Sex-adjusted OR 3.2, 95% CI 2.1 to 4.7).
In a prospective, population-based study, Swartz et al examined the relationship between specific psychiatric disorders and migraine. The study sample included 1,343 participants identified from the Baltimore, MD cohort of the Epidemiologic Catchment Area Study. In cross-sectional analyses, major depression was strongly associated with migraine (OR 3.1, 95% CI 2.0 to 4.8).
Zwart et al conducted a large, cross-sectional population-based study to examine the association between migraine, non-migrainous headache, and headache frequency. Data were derived from the Nord-Trondelag Health Study, conducted in Nord-Trondelag County, Norway. The study sample included more than 50,000 participants. Data were collected through questionnaires. Headache diagnoses were based on IHS criteria, and mental assessment was based on HADS, a 2-dimensional self-rating instrument for depression (HADS-D) and anxiety (HADS-A). In this study, the OR for depression was significantly higher in people with migraine and non-migrainous headache, compared to headache-free individuals (non-migrainous headache OR 2.2, 95% CI 2.0 to 2.5; migraine headache OR 1.9, 95% CI 1.6 to 2.3). In addition, there was a strong linear trend (P < .001) of higher prevalence OR of depression with increasing headache frequency.
A study reported by McWilliams et al used data from the Midlife Development in the United States Survey to investigate associations between 3 pain conditions (arthritis, migraine, and back pain) and 3 common psychiatric disorders (depression, panic attacks, and generalized anxiety disorder) in a large sample (n = 3,032) of adults aged 25 to 74 in the U.S. general population. In this population, 28.5% of subjects with migraine were considered clinically depressed, while only 12.3% of subjects without migraine fit the same criteria (OR 2.8, 95% CI 2.2 to 3.7).
Patel et al studied the prevalence of major depression in individuals with migraine, probable migraine (a subtype of migraine missing just one migraine feature), and controls. Participants were identified from members of a mixed model health maintenance organization (HMO) using computer-assisted telephone interviews. The overall prevalence of major depression was 28.1% for persons with migraine, 19.5% for those with probable migraine, and 10.3% for the control group. The prevalence of major depression was elevated in all migraine groups when compared with controls on both crude and adjusted (by age, sex, education) prevalence ratios.
Several studies have examined the bidirectional associations of migraine and depression. Three of these studies found a positive association while one found no association. In 1994, Breslau et al examined the association between migraine and depression in a prospective sample of 1,007 adults between the ages of 21 and 30 years. Subjects were members of a large HMO in Southeast Michigan. Using the Cox proportional hazards model, the sex- and education-adjusted HR for new-onset migraine in subjects with major depression was 3.1 (95% CI 2.0 to 5.0). Conversely, the sex- and education-adjusted HR for new-onset major depression in subjects with migraine was 3.2 (95% CI 2.3 to 4.6).
In 2000, Breslau et al reported a HR of 2.4 (95% CI 1.8 to 3.0) for first onset of major depression associated with previous migraine, controlling for sex. The HR for the reverse association: onset of migraine associated with previous major depression was 2.8 (95% CI 2.2 to 3.5). This study also investigated the bidirectional relationship between severe headache and major depression. The HR was significant for severe headaches and first-onset major depression (3.6, 95% CI 2.4 to 5.3), but not for major depression and first occurrence of migraine (1.6, 95% CI 0.9 to 2.8).
Breslau et al reported similar results in a 2-year longitudinal population-based cohort from the Detroit metropolitan area. The results of this study showed that, over a 2-year period, having baseline depression increased the risk of incident migraine (OR 3.4, 95% CI 1.4 to 8.7), but not other severe headaches (OR 0.6, 95% CI 0.1 to 4.6). In addition, the risk of incident depression was significantly higher in those with baseline migraine (OR 5.8, 95% CI 2.7 to 12.3), but not in those with severe headaches (OR 2.7, 95% CI 0.9 to 8.1). These results, in combination with those reported by Breslau et al in 2000, suggest that the bidirectional relationship is specific to migraine, and not all severe headaches.
In contrast, Swartz et al reported no excess incidence of adult-onset migraine among people with pre-existing depression (Age- and sex-adjusted OR 0.68, 95% CI 0.02 to 2.0). This study did not assess the onset of depression among people with pre-existing migraine. In addition, this study did not obtain data about subjects’ history of migraine at baseline, and it excluded all people with a history of unspecified headache (21% of the sample). Subjects with a history of unspecified headache were considered not at risk for the first onset of migraine during the follow-up period. This exclusion is likely to lead to underestimation of the relationship between depression and first-onset migraine. Other explanations for the inconsistency of results between these studies include: differences in the samples ages, length of recall period, assessment procedures, and the definition of people at risk for first-onset migraine.
Migraine and depression are comorbid: in large scale population-based studies, persons with migraine are from 2.2 to 4.0 times more likely to have depression. Some studies support a bidirectional relationship between migraine and depression, with each disorder increasing the risk for the subsequent first onset of the other. In the studies that report a bidirectional relationship, the risk of first-onset migraine in people with pre-existing depression ranged from 2.8 to 3.5 in the studies we sampled. Conversely, the risk of first onset of depression in people with pre-existing migraine ranged from 2.4 to 5.8. While Swartz did not support the bidirectional relationship, we believe that methodologic limitations may account for the negative study. These findings have important implications for clinical practice. Patients with migraine or depression should be evaluated for the other disorder. In addition, for patients with co-existing conditions, treatment choices that might improve both conditions should be considered.
Sandra W. Hamelsky, PhD, MPH, The Bradstreet Group, 1588 Route 130 North, North Brunswick, NJ 08902, USA
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA (Drs. Hamelsky and Lipton); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA (Dr. Hamelsky); and Montefiore Headache Center, New York, NY, USA (Dr. Lipton).
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