Agomelatine Treatment of Major Depressive Disorder

OBJECTIVE: To review the efficacy, safety, pharmacologic, and pharmacokinetic data of agomelatine to better understand its potential role in the treatment of patients with major depressive disorder. DATA SOURCES: A MEDLINE search (1966-October 2008) was conducted using the following terms: agomelatine, antidepressant, S20098, melatonin, serotonin, 5-HT2C, MT, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, receptor binding, depression, major depressive disorder, and mood disorder. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Randomized, controlled trials involving humans were prioritized in the review. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. DATA SYNTHESIS: Agomelatine, a potent agonist at type 1 and 2 melatonin receptors, selectively inhibits serotonin. It is extensively metabolized via cytochrome P450 isoenyzmes 1A1, 1A2, and 2C9 to metabolites with less activity than the parent drug. Five randomized controlled studies were identified that examined the efficacy and safety of agomelatine in major depressive disorder. In general, agomelatine was found to produce significant improvements in depressive symptoms compared with placebo on many, but not all, rating scales. Three of the trials had active comparator arms (ie, venlafaxine, paroxetine). In these 3 investigations, agomelatine produced effects on depressive symptoms similar to those of the comparator drugs. A small number of studies have demonstrated sleep benefits with the use of agomelatine in depressed patients. Positive findings also exist for the use of agomelatine in seasonal affective disorder and bipolar depression. The most common adverse effects reported with agomelatine use were headache, nasopharyngitis, and gastrointestinal complaints. The magnitude of agomelatine-related adverse effects appears to be at least similar to some currently marketed antidepressants. CONCLUSIONS: Overall, agomelatine is a promising and well-tolerated medication for the treatment of major depressive disorder. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy and safety of agomelatine.