Agomelatine prevents relapse in patients with major depressive disorder without evidence of a discontinuation syndrome: a 24-week randomized, double-blind, placebo-controlled trial.
OBJECTIVE
This study evaluates the efficacy of agomelatine, the first antidepressant that is an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptor, in the prevention of relapse of depression following successful response.


METHODS
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 > or = 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.


BACKGROUND
isrctn.org Identifier: ISRCTN53193024.
Goodwin
Guy M
GM
Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford, United Kingdom OX3 7JX, UK. guy.goodwin@psych.ox.ac.uk
Emsley
Robin
R
Rembry
Sandra
S
Rouillon
Frédéric
F
D000081:Acetamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000517:prevention & control*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008550:Melatonin / Q000819:agonists*; D008875:Middle Aged; D044122:Receptor, Melatonin, MT1 / Q000819:agonists; D044123:Receptor, Melatonin, MT2 / Q000819:agonists; D055502:Secondary Prevention; D058830:Serotonin 5-HT2 Receptor Antagonists; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome; D009281:Naphthalenes
D000081:Acetamides; D006993:Hypnotics and Sedatives; D008550:Melatonin; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes