Agomelatine: a novel pharmacological approach to treating depression.

Abstract

Agomelatine is a melatonin analogue which represents a novel class of antidepressants. It acts as an agonist at melatonin MT(1) and MT(2) receptors and as a specific antagonist at 5-HT(2C) receptors. It is rapidly absorbed orally and mainly metabolized via CYP1A2 hepatic isoenzymes, has no active metabolites and an elimination half-life of 1-2 hours. Short-term trials (6-8 weeks) have confirmed the compound's antidepressant effect in major depressive disorder at doses of 25-50 mg/day. It has comparable antidepressant activity to venlafaxine (75-150 mg/day) and in one trial, showed statistical superiority to sertraline 50-100 mg/day. In long-term studies agomelatine was superior to placebo for relapse prevention at 10 months and treatment adherence rates were higher than with venlafaxine and sertraline over 6 months. The drug has anxiolytic properties and a beneficial effect on sleep without affecting rapid eye movement (REM) activity. Although agomelatine is generally well tolerated with low adverse event discontinuation rates, it currently requires monitoring of liver function because a small number of patients had raised liver enzyme activities in the trial program. The compound has fewer effects on sexual function than venlafaxine and, unlike paroxetine, it causes minimal discontinuation symptoms upon abrupt withdrawal. Agomelatine is currently being investigated for other indications such as seasonal affective disorder, generalized anxiety disorder and bipolar depression.