Agomelatine prevents relapse in generalized anxiety disorder: a 6-month randomized, double-blind, placebo-controlled discontinuation study.
OBJECTIVE
This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder (GAD).


METHODS
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.


BACKGROUND
www.isrctn.org identifier: ISRCTN38094599.
Department of Psychiatry, Groote Schuur Hospital, Cape Town, South Africa. dan.stein@uct.ac.za
Dan J
DJ
Stein
Antti
A
Ahokas
Cristina
C
Albarran
Valérie
V
Olivier
Christer
C
Allgulander
D000081:Acetamides / Q000009:adverse effects* / Q000627:therapeutic use*; D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D057915:Drug Substitution; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory / Q000706:statistics & numerical data; D011594:Psychometrics; D012307:Risk Factors; D055502:Secondary Prevention; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D009281:Naphthalenes
D000081:Acetamides; D006993:Hypnotics and Sedatives; C084711:agomelatine; D009281:Naphthalenes