Agomelatine prevents relapse in generalized anxiety disorder: a 6-month randomized, double-blind, placebo-controlled discontinuation study

J Clin Psychiatry. 2012 Jul;73(7):1002-8. doi: 10.4088/JCP.11m07493.

Abstract

Objective: This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder (GAD).

Method: Patients with GAD (Hamilton Anxiety Rating Scale [HARS] ≥ 22, with items 1 and 2 ≥ 2, item 1 + 2 ≥ 5; Montgomery-Asberg Depression Rating Scale [MADRS] ≤ 16; and < 20% decrease in HARS total score between screening and baseline) who responded to a 16-week course of agomelatine 25-50 mg/d treatment were randomly assigned to receive continuation treatment with agomelatine (n = 113) or placebo (n = 114) for 26 weeks. The main outcome measure was time to relapse during this maintenance period. The estimated risk of relapse was calculated using the Kaplan-Meier method, and groups were compared using a log-rank test stratified for country. The study was undertaken in 31 clinical centers in Canada, Denmark, Estonia, Finland, Hungary, and Sweden from November 2007 to September 2009.

Results: During the 6-month maintenance period, the proportion of patients that relapsed during the double-blind period in the agomelatine group (22 patients, 19.5%) was lower than in the placebo group (35 patients, 30.7%). The risk of relapse over time was significantly lower for patients who continued treatment than for those switched to placebo (P = .046, log-rank test stratified for country). Agomelatine was also superior to placebo in preventing relapse in the subset of more severe patients with baseline HARS total score ≥ 25 and CGI-S score ≥ 5. The tolerability of agomelatine was good throughout the study, and there were no differences in discontinuation symptoms after withdrawal of agomelatine in comparison to maintenance on agomelatine.

Conclusions: The present study extends the positive findings of an earlier short-term study of agomelatine in GAD, demonstrating that agomelatine is effective and well-tolerated in the longer-term treatment of this chronic disorder.

Trial registration: www.isrctn.org identifier: ISRCTN38094599.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / adverse effects*
  • Acetamides / therapeutic use*
  • Adult
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Substitution
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Hypnotics and Sedatives / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Personality Inventory / statistics & numerical data
  • Psychometrics
  • Risk Factors
  • Secondary Prevention
  • Substance Withdrawal Syndrome / etiology*

Substances

  • Acetamides
  • Hypnotics and Sedatives
  • agomelatine

Associated data

  • ISRCTN/ISRCTN38094599