Agomelatine in the Treatment of Major Depressive Disorder: An 8-Week, Multicenter, Randomized, Placebo-Controlled Trial

Objective: To evaluate the efficacy, safety, and tolerability of fixed-dose agomelatine 25 and 50 mg/d in the treatment of outpatients with moderate-to-severe major depressive disorder (MDD) compared to placebo.

Method: In this 8-week, multicenter, double-blind, parallel-group trial, patients with DSM-IV-defined MDD were randomly assigned (1:1:1) to receive a once-daily dose of agomelatine 25 mg, agomelatine 50 mg, or placebo. The primary efficacy measure was the change from baseline to week 8 in the clinician-rated 17-item Hamilton Depression Rating Scale (HDRS17); other efficacy measures were the clinical remission and response rates (measured by HDRS17), Clinical Global Impressions scales, Hospital Anxiety and Depression Scale (HADS) score, subjective measures on sleep, and the overall quality of life. The study was conducted between December 2006 and January 2008.

Results: Agomelatine 25 mg/d was more efficacious based on the HDRS17 total score (P’ ‰=’ ‰.01) compared to placebo throughout the treatment period, whereas for agomelatine 50 mg/d, statistically significant reduction in HDRS17 total score could be observed from weeks 2 to 6 but not at week 8 (P’ ‰=’ ‰.144). A higher proportion of patients receiving agomelatine 25 mg/d showed clinical response (P’ ‰=’ ‰.013), clinical remission (P’ ‰=’ ‰.07), and improvement according to the Clinical Global Impressions-Improvement scale (P’ ‰=’ ‰.065) compared to those receiving placebo. No statistically significant difference between patients receiving agomelatine 50 mg/d compared to placebo on clinical response (P’ ‰=’ ‰.116) or clinical remission (P’ ‰=’ ‰.457) was observed. HADS score, quality of sleep, and quality of life significantly improved with agomelatine 25 mg/d compared to placebo. Both agomelatine doses were safe and well tolerated, although clinically notable aminotransferase elevations were observed transiently in the agomelatine 50 mg/d group.

Conclusions: Agomelatine 25 mg/d was effective in the treatment of patients with moderate-to-severe MDD and was safe and well tolerated. Agomelatine 50 mg/d provided evidence for its antidepressant efficacy until week 6 and was also safe and well tolerated.

Trial Registration: clinicaltrials.gov Identifier: NCT00411242

J Clin Psychiatry

Submitted: June 19, 2009; accepted August 27, 2009.

Online ahead of print: March 23, 2010 (doi:10.4088/JCP.09m05471blu).

Corresponding author: Stephen M. Stahl, MD, PhD, 1930 Palomar Point Way, Ste 103, Carlsbad, CA 92008 ([email protected]).