Abstract
SummaryAgomelatine 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-HT2C 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-HT2C 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.
Highlights
Declaration of interest P.J.C. has been a paid member of advisory boards for Eli Lilly, Lundbeck and Servier
Controlled studies have suggested favourable efficacy and tolerability profiles; agomelatine is not without its controversies, with recent meta-analyses showing only marginal advantages over placebo. It is an intriguing agent pharmacologically and here we provide a synopsis of its proposed mechanisms of action, indications and side-effects in the treatment of unipolar major depression
Agomelatine is an interesting antidepressant with a novel mode of action
Summary
Summary 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-HT2C receptors. Current meta-analyses show marginal clinical benefits of agomelatine relative to placebo and an association with occasional increases in liver transaminases It is not clear whether agomelatine does block brain 5-HT2C receptors in humans at therapeutic doses and the optimum daily timing of administration in depression has not been clearly established. Controlled studies have suggested favourable efficacy and tolerability profiles; agomelatine is not without its controversies, with recent meta-analyses showing only marginal advantages over placebo. It is an intriguing agent pharmacologically and here we provide a synopsis of its proposed mechanisms of action, indications and side-effects in the treatment of unipolar major depression
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