Major depressive disorders: clinical efficacy and tolerability of agomelatine, a new melatonergic agonist

SummaryAgomelatine is a new antidepressant with an innovative pharmacological profile. It is a potent melatonergic agonist (MT1 and MT2) and also has 5-HT2c antagonist properties. Agometatine's efficacy in treating major depressive disorder (MDD) was first described in a placebo-controlled, dose-ranging study with paroxetine as a validator. In a recent placebo-controlled study, 212 MDD patients were randomly assigned double-blind to receive placebo or agomelatine 25 and 50 mg/day. There was a significant advantage for agomelatine after 6 weeks according to scores on the Hamilton Depression Rating Scale (HAM-D) (P = 0.026) and the Clinical Global Impression Severity (P = 0.017), with an improved response rate (P = 0.03). Robust evidence of agomelatine's efficacy in severe depression comes from analysis of a patient subgroup with baseline HAM-D scores >25. Analysis of pooled data from three different trials confirmed this observation and suggested that the agomelatine-placebo difference tends to increase with the severity of depression. Results suggest favorable tolerabitity of agomelatine compared with a serotonin and noradrenaline reuptake inhibitor, and agomelatine is associated with less sexual side effects that are troublesome with some antidepressants. As predicted from its pharmacological profile, agomelatine improves sleep quality without associated daytime drowsiness. Agomelatine was also shown not to induce a discontinuation syndrome. Agomelatine may fill the gap in the current therapeutic armamentarium by combining efficacy with a favorable tolerability profile and additional clinical benefits.