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.

Neuroinflammation and the Immune-Kynurenine Pathway in Anxiety Disorders

“…Furthermore, the combined treatment of ineffective doses of melatonin and diazepam has been reported to show an anxiolytic-like effect [ 55 ]. In recent human studies, agomelatine, a melatonergic receptor agonist, was effective in the treatment of generalized anxiety disorder [ 56 , 57 ]. The agomelatine also demonstrated efficacy in the treatment of panic disorder [ 58 , 59 ].…”

Treatment of anxiety disorders

“…The antidepressant agomelatine-which acts as an agonist for melatonin MT 1 and MT 2 receptors and as an antagonist for serotonin 5-HT 2C receptors-was shown to be effective in four studies in GAD. [55][56][57][58] However, the drug is only licensed for the treatment of major depression, not for GAD. With agomelatine, discontinuation symptoms 59,60 and sexual dysfunction 61 are less likely than with SSRI or SNRI antidepressants.…”

Agomelatine for the Treatment of Generalized Anxiety Disorder: A Meta-Analysis

“…All studies were multi-centered, multinational trials conducted outside of US. Three were short-term clinical trials with 12 weeks of study duration [ 17 , 28 , 29 ]. One trial involved a 26-week double-blinded, placebo-controlled trial in GAD patients who showed optimal remission with agomelatine [ 18 ].…”

“…Three studies used identical dose of agomelatine, 25−50 mg/day [ 17 , 18 , 28 ]. However, in one study, the agomelatine group was further randomized into agomelatine 10 mg/day or 25 mg/day [ 29 ].…”