title: Efficacy and safety of agomelatine (10 or 25 mg/day) in non-depressed out-patients with generalized anxiety disorder: A 12-week, double-blind, placebo-controlled study.
abstract: Agomelatine is efficacious in reducing symptoms and preventing relapse in placebo-controlled trials in generalised anxiety disorder (GAD). Nevertheless, fixed dose studies of agomelatine in GAD have not been undertaken. To determine the minimally effective optimal dose of agomelatine in GAD, the efficacy of two doses of agomelatine (10 and 25mg/day) was investigated in a 12-week, placebo-controlled, double-blind, international study in patients with a primary diagnosis of GAD. The primary outcome measure was the Hamilton Anxiety scale (HAM-A). The study was undertaken in 35 clinical centers in Finland, Russia, Poland, Slovakia and Ukraine from August 2013 to January 2015. 131 out-patients were included in the agomelatine 10mg group, 139 in the agomelatine 25mg group, and 142 in the placebo group. Both doses of agomelatine were associated with significant decreases in the HAM-A at week 12 (difference versus placebo of 7.16±1.00 at 10mg and 11.08±0.98 at 25mg, p<0.0001). Significant effects on all secondary measures were found for both doses at week 12; including psychic and somatic HAM-A subscales, response rate, remission on the HAM-A, and functional impairment. Findings were confirmed in subsets of more severely ill patients on all endpoints. The low placebo response rate observed in this study was consistent with an increase in the quality of data collected. Agomelatine was well-tolerated by patients, with minimal distinctions from placebo. There was a dose effect of agomelatine, with a greater placebo-agomelatine difference in the agomelatine 25mg group, compared to the agomelatine 10mg group.The present data support early work indicating the efficacy and tolerability of agomelatine in the treatment of GAD.
authors.affiliation: University of Cape Town Department of Psychiatry & MRC Unit on Anxiety & Stress Disorders, Groote Schuur Hospital, J-Block, Anzio Road, Cape Town 7925, South Africa. Electronic address: dan.stein@uct.ac.za.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
authors.affiliation: Mehilainen Clinic, Runeberginkatu 47 A, 00260 Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Ahokas
authors.affiliation: Institute of Psychiatry and Neurology, 3rd Department of Psychiatry, Warszawa, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Jarema
authors.affiliation: Serbsky National Research Centre for Social and Forensic Psychiatry, Moscow, Russia.
authors.forename: Alla S
authors.initials: AS
authors.lastname: Avedisova
authors.affiliation: Private Psychiatric Practice - VAVRUŠOVÁ CONSULTING s.r.o., Záporožská 12, 851 01 Bratislava, Slovakia.
authors.forename: Livia
authors.initials: L
authors.lastname: Vavrusova
authors.affiliation: Psychosomatic Medicine and Psychotherapy, National Medical University Named After O.O. Bogomolets, M. Kotsyubynskogo 8A str., 01030 Kiev, Ukraine.
authors.forename: Oleg
authors.initials: O
authors.lastname: Chaban
authors.affiliation: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gruget
authors.affiliation: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Olivier
authors.affiliation: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Picarel-Blanchot
authors.affiliation: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Christian
authors.initials: C
authors.lastname: de Bodinat
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D016896:Treatment Outcome; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D006993:Hypnotics and Sedatives; C084711:agomelatine; D009281:Naphthalenes
keywords: Agomelatine; Generalized anxiety disorder; Placebo