Comorbidity of migraine and depression: Investigating potential etiology and prognosis

Background: An association between migraine and major depression has been observed in clinical and community samples. The factors that contribute to this association and their implications remain unclear. Objective: To determine the factors contributing to the association of migraine and major depression. Methods: A cohort study of persons aged 25 to 55 years with migraine (n = 496) or with other headaches of comparable severity (n = 151) and control subjects with no history of severe headaches (n = 539) randomly selected from the general community were interviewed first in 1997 and then reinterviewed in 1999. Results: Major depression at baseline predicted the first-onset migraine during the 2-year follow-up period (odds ratio [OR] = 3.4; 95% CI = 1.4, 8.7) but not other severe headaches (OR = 0.6; 95% CI = 0.1, 4.6). Migraine at baseline predicted the first-onset major depression during follow-up (OR = 5.8; 95% CI = 2.7, 12.3); the prospective association from severe headaches to major depression was not significant (OR = 2.7; 95% CI = 0.9, 8.1). Comorbid major depression did not influence the frequency of migraine attacks, their persistence, or the progression of migraine-related disability over time. Conclusions: Major depression increased the risk for migraine, and migraine increased the risk for major depression. This bidirectional association, with each disorder increasing the risk for first onset of the other, was not observed in relation to other severe headaches. With respect to other severe headaches, there was no increased risk associated with pre-existing major depression, although the possibility of an influence in the reverse direction (i.e., from severe headaches to depression) cannot be securely ruled out.