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Original Research

Agomelatine in Generalized Anxiety Disorder: An Active Comparator and Placebo-Controlled Study

Dan J. Stein, MD, PhD; Antti Ahokas, MD; Miguel S. Márquez, MD; Cyril Höschl, MD; Kang Seob Oh, MD; Marek Jarema, MD; Alla S. Avedisova, MD; Cristina Albarran, PharmD; and Valérie Olivier, PharmD, PhD

Published: February 18, 2014

Article Abstract

Background: Agomelatine was efficacious in reducing symptoms in a short-term placebo-controlled trial in generalized anxiety disorder (GAD) and in preventing relapse in a longer term placebo-controlled study. An additional short-term placebo-controlled study is required by regulatory agencies to confirm the efficacy of agomelatine in GAD.

Method: This 12-week, placebo-controlled, double-blind, randomized, parallel group, international, multicenter study was designed to confirm the efficacy of agomelatine 25-50 mg/d in the treatment of patients with a primary DSM-IV-TR diagnosis of GAD. The primary outcome measure was the Hamilton Anxiety Rating Scale (HARS) total score. Assay sensitivity was evaluated by including an escitalopram (10-20 mg/d) group.

Settings: The study was undertaken in 45 clinical centers in Argentina, Czech Republic, Finland, South Korea, Poland, Russia, and Slovakia from April 2010 to July 2011.

Results: One hundred thirty-nine outpatients were included in the agomelatine group, 131 in the placebo group, and 142 in the escitalopram group. Agomelatine significantly reduced mean (SD) HARS total score (agomelatine-placebo difference: 4.71 [1.03], P < .0001) and had significant effects on secondary outcome measures, including psychic and somatic HARS subscales, response rate (estimate [standard error]) (agomelatine-placebo difference: 27.4% [5.9%], P < .0001), remission on the HARS (agomelatine-placebo difference: 16.8% [5.4%], P = .002), Clinical Global Impressions-Severity of Illness scale (CGI-S) (P < .001), functional impairment (P < .0001), and sleep quality (P < .001). Findings were confirmed in the subset of more severely ill patients (HARS total score ≥ 25 with or without CGI-S ≥ 5 at baseline). Agomelatine was well tolerated by patients, with no more adverse events than placebo. Escitalopram was similarly efficacious but was accompanied by a higher incidence of adverse events compared to placebo.

Conclusions: In clinical practice, agomelatine has at least similar efficacy to that of escitalopram for the short-term treatment of GAD and is well tolerated.

Trial Registration: identifier: ISRCTN03554974

J Clin Psychiatry

Submitted: February 18, 2013; accepted August 21, 2013.

Online ahead of print: February 18, 2014 (doi:10.4088/JCP.13m08433).

Corresponding author: Dan J. Stein, MD, PhD, University of Cape Town Department of Psychiatry, Groote Schuur Hospital, J-Block, Anzio Rd, Observatory, Cape Town 7925, South Africa (

Volume: 75

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