Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta‐analysis

Background and purpose Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature. Methods A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index. Results Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of −0.79 [95% confidence interval (CI) −1.13 to −0.45, P < 0.00001]. Patients receiving antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97–2.02; P = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05–2.89, P = 0.03). Conclusions Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky.