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Migraine headache is a highly prevalent, often severely painful and frequently disabling disorder. The indirect costs related to disability greatly exceed the direct cost of medical care. The objective of this paper is to describe work-related disability associated with migraine headache and predictors of disability. In a two-stage survey of the US population, we estimate missed workdays and impairment at work in a sample of 1663 migraine sufferers, age 18 years and older. Lost workday equivalents (LWDE) was derived as the sum of actual missed workdays and the product of percentage effectiveness at work and days at work with the most severe headache. Overall, reported actual lost workdays and reduced effectiveness at work contributed approximately equally to total LWDE. A total of 51.1% of females and 38.1% of male migraineurs experienced six or more LWDE per year. This subgroup of migraine sufferers accounted for about 90% of the total LWDE experienced by all respondents. Among women, headache duration was the strongest predictor of LWDE followed by less significant associations with number of symptoms and pain level. Among men, only pain level was significantly associated with LWDE. Among sociodemographic factors, disability was more likely among older (40+) subjects and less likely among individuals with higher education and higher income (females only), even after adjusting for headache features. Health-care interventions may yield the greatest individual benefit (by reducing pain and disability) and the greatest societal benefit (by reducing indirect costs) if they are directed to those who account for the greatest proportion of disability.