The mechanism,efficacy, and tolerability profile of agomelatine

Introduction: Agomelatine is a novel antidepressant that acts as a melatonin MT₁ and MT₂ receptor agonist and serotonin 5-HT_2C receptor antagonist, putatively reversing circadian rhythm disruption in major depressive disorder (MDD) and promoting dendritic neurogenesis in animal models of depression. It may be a preferable alternative to antidepressants currently in use due to its improved tolerability profile.

Areas covered: The PubMed database was searched for published randomized controlled trials (RCTs) evaluating the efficacy of agomelatine as well as its tolerability and safety in the treatment of MDD. The key search term used was agomelatine combined with major depressive disorder/depressive disorder/depression and antidepressant. Article selection was based upon sample size and overall methodological quality.

Expert opinion: Agomelatine is a multi-modal agent with novel mechanisms of action, having sound evidence supporting its overall statistical efficacy and adequate tolerability profile for MDD treatment. However, the clinical significance of agomelatine has been contested, calling for additional studies in evaluation of its effect size. Of further concern are reported transient elevations in transaminases and severe but rare liver reactions.