Agomelatine Prevents Relapse in Patients With Major Depressive Disorder Without Evidence of a Discontinuation Syndrome: A 24-Week Randomized, Double-Blind, Placebo-Controlled Trial
J Clin Psychiatry 2009;70(8):1128-1137
© Copyright 2015 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
Objective: This study evaluates the efficacy of agomelatine, the first antidepressant that is an agonist at MT1/MT2 receptors and an antagonist at 5-HT2C receptor, in the prevention of relapse of depression following successful response.
Method: Patients with DSM-IV-TR major depressive disorder who responded to an 8- or 10-week course of agomelatine 25- or 50-mg daily treatment were randomly assigned to receive continuation treatment with agomelatine (n = 165) or placebo (n = 174) during a 24-week, randomized, double-blind treatment period. The main outcome measure was time to relapse during the double-blind treatment period. The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis. The study was conducted from February 2005 to February 2007.
Results: During the 6-month evaluation period, the incidence of relapse was significantly lower in patients who continued treatment than in those switched to placebo (P = .0001). The cumulative relapse rate at 6 months for agomelatine-treated patients was 21.7%; that for placebo-treated patients was 46.6%. Agomelatine was also superior to placebo in preventing relapse in the subset of patients with baseline 17-item Hamilton Depression Rating Scale total score ≥ 25. Measures of tolerability and safety of both doses of agomelatine were similar to placebo. No pattern of early relapse or adverse events suggestive of withdrawal symptoms was obtained after abrupt cessation of agomelatine.
Conclusions: The findings are important in 2 respects. First, agomelatine is an effective and safe antidepressant continuation therapy, which confirms efficacy seen in short-term studies. Second, few early relapses were observed in the patient group switched to placebo: the survival curve for placebo separated gradually from that of patients taking agomelatine. We suggest this reflects solely the underlying properties of the illness, which is only possible due to the lack of discontinuation syndrome after agomelatine withdrawal. It underlines the novel clinical profile of agomelatine, which quite likely reflects its innovative pharmacology.
Trial Registration: isrctn.org Identifier: ISRCTN53193024
Submitted: July 15, 2008; accepted October 9, 2008.
Online ahead of print: August 11, 2009.
Corresponding author: Guy M. Goodwin, FMedSci, FRCPsych, Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford, United Kingdom OX3 7JX (firstname.lastname@example.org).