Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study.
BACKGROUND
Agomelatine is a novel agent that acts on melatonergic (MT(1), MT(2)) receptors and serotonergic (5-HT(2C)) receptors. Preclinical data and data from clinical trials in major depression suggest that agomelatine may have anxiolytic properties. A randomized, double-blind, placebo-controlled trial was designed to assess the efficacy of agomelatine in generalized anxiety disorder (GAD).


METHODS
One hundred twenty-one patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition GAD and no comorbid disorders were randomized to agomelatine (25-50 mg/d) or placebo for 12 weeks. The primary outcome measure was the Hamilton Anxiety Rating Scale, whereas secondary outcome measures included the Clinical Global Impression scales, the Leeds Sleep Evaluation Questionnaire, and the Sheehan Disability Scale. Safety measures included assessment of spontaneously reported adverse events, laboratory monitoring, and the Discontinuation Emergent Signs and Symptoms Scale to evaluate discontinuation symptoms.


RESULTS
Analysis of covariance of change in the last Hamilton Anxiety Rating Scale total score from baseline demonstrated significant superiority of agomelatine 25 to 50 mg as compared with placebo (E [SE] = -3.28 [1.58]; 95% confidence interval = -6.41 to -0.15; P = 0.040). Data on secondary outcome measures, including clinical response, symptoms of insomnia, and improvement in associated disability, were consistent with the efficacy of agomelatine. Safety analysis indicated that agomelatine was tolerated as well as placebo and was devoid of discontinuation emergent symptoms.


CONCLUSIONS
This study suggests that agomelatine is effective in the treatment of GAD and is well tolerated. Additional trials, using an active comparator and extending over a longer period, are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for anxiety disorders.
Stein
Dan J
DJ
Department of Psychiatry, University of Cape Town, South Africa. dan.stein@uct.ac.za
Ahokas
Antti A
AA
de Bodinat
Christian
C
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D044122:Receptor, Melatonin, MT1 / Q000819:agonists; D044123:Receptor, Melatonin, MT2 / Q000819:agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D016896:Treatment Outcome; D009281:Naphthalenes
D000081:Acetamides; D006993:Hypnotics and Sedatives; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes