Drug information update: agomelatine

Abstract

Agomelatine is a new antidepressant, licensed for the treatment of unipolar major depression, with a mode of action that combines activation of melatonin receptors with blockade of 5-HT 2C receptors. Agomelatine is notable for its short duration of action in the body and modest side-effect burden; however, a number of theoretical and practical challenges have limited its adoption into mainstream treatment in the UK. Current meta-analyses show marginal clinical benefits of agomelatine relative to placebo and an association with occasional increases in liver transaminases. Theoretically it is not clear whether agomelatine does block brain 5-HT 2C receptors in humans at therapeutic doses and the optimum daily timing of administration in depression has not been clearly established. However, agomelatine’s novel mode of action justifies further study, perhaps with the eventual aim of matching its use in depression to patients with specific disturbances in circadian rhythm.