Evidence of new-onset depression among persons with migraine after discontinuing antidepressants

Antidepressants have been hypothesized to cause tardive dysphoria-the delayed development of negative emotional symptoms. We assessed the risk of tardive dysphoria in a cohort of persons with migraine taking anti-migraine antidepressants with no known diagnosis of any mood or anxiety disorder. We included all outpatient encounters in a university hospital system for migraine from January 2008 through October 2018, excluding subjects with prior psychiatric diagnoses. Kaplan-Meier survival curves and multivariable Cox proportional hazards analyses were conducted. 13,048 subjects were included; 1191 took an antidepressant; 402 discontinued an antidepressant. In multivariable analyses examining the first year after exposure, antidepressant use was not significantly associated with risk of a depression, any mood disorder (including depression, mania, and other mood disorders), or anxiety. Antidepressant discontinuation was significantly associated with increased risk of depression, but not any mood disorder or anxiety. Among persons with migraine with no known psychiatric diagnosis, antidepressants did not appear to be associated with indicators of tardive dysphoria. Antidepressant discontinuation, however, was associated with increased risk of a depression diagnosis.