The International Journal of Neuropsychopharmacology

Research Article

Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder

Jean Pierre Oliéa1 c1 and Siegfried Kaspera2

a1 Sainte Anne Hospital, University Department of Psychiatry, Paris, France

a2 Department of General Psychiatry, Medical University of Vienna, Vienna, Austria

Abstract

Current antidepressants used in major depressive disorder (MDD) are still not efficacious enough for many patients due to high levels of treatment resistance and bothersome side-effects. Using a novel blinding method (interactive voice response system), this flexible-dosing study examined the effects of therapeutic doses of agomelatine, a new approach to depressive therapy offering potent melatonergic MT1/MT2 receptor agonism with 5-HT2C receptor antagonist properties, in patients with moderate-to-severe MDD. This 6-wk, double-blind, parallel-group study randomized 238 patients to 25 mg/d agomelatine (with dose adjustment at 2 wk to 50 mg/d in patients with insufficient improvement) or placebo. Depression severity was assessed using the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression (CGI) scale. Agomelatine was significantly more efficacious than placebo, with an agomelatine–placebo difference of 3.44 (p<0.001) using the HAMD final total score. Compared with placebo, agomelatine also had a significant positive impact on CGI – Improvement (treatment difference=0.45) and CGI – Severity (treatment difference=0.50) (both p=0.006), response rate (54.3% vs. 35.5% with placebo, p<0.05) and time to first response (p=0.008). Similar results were seen in patients with the most severe MDD. Depressed mood and sleep items of the HAMD were also significantly improved with agomelatine, which was well tolerated with a safety profile similar to placebo at both doses. This study confirms that agomelatine is effective in treating major depression, including the most severely depressed patients, with a good safety and tolerability profile, therefore providing physicians with an effective pharmacological approach to antidepressant therapy.

(Received October 05 2006)

(Reviewed December 08 2006)

(Revised March 05 2007)

(Accepted March 18 2007)

(Online publication May 04 2007)

Correspondence:

c1 Address for correspondence: Professor Jean Pierre Olié, Sainte Anne Hospital, University Department of Psychiatry, 7 rue Cabanis, 75684 Paris Cedex 14, France. Tel.: +33 1 45658452 Fax: +33 1 45658160 E-mail: jp.olie@ch-sainte-anne.fr