Agomelatine: an antidepressant with a novel mechanism of action

Abstract

Despite advances in understanding potential disease mechanisms in depression and in therapeutic approaches to the management of major depressive disorder, the disease continues to carry an enormous personal, social and economic burden. Agomelatine is a melatonergic antidepressant with melatonin (MT1 and MT2) agonistic and serotonin (5-HT2C) antagonistic properties. It represents a promising approach to treating depression through a unique synergistic mechanism. There is also preliminary evidence to suggest that agomelatine has anxiolytic properties in depressed patients. Clinical data confirm that agomelatine, in a dose range of 25–50 mg daily, is an effective antidepressant with a very favorable side-effect profile. In particular, sleep restorative effects in the absence of daytime sedation and a favorable effect on sexual function suggest that agomelatine will offer a high efficacy–tolerability index for patients with major depressive disorder. Such results have been anticipated based on preclinical studies using various animal models of both depression and anxiety.