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.


METHODS
A MEDLINE search (1966-October 2008) was conducted using the following terms: agomelatine, antidepressant, S20098, melatonin, serotonin, 5-HT(2C), MT, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, receptor binding, depression, major depressive disorder, and mood disorder.


METHODS
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.


RESULTS
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.
Dolder
Christian R
CR
School of Pharmacy, Wingate University, Wingate, NC 28174, USA. cdolder@wingate.edu
Nelson
Michael
M
Snider
Morgan
M
D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D044094:Receptors, Melatonin / Q000819:agonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D009281:Naphthalenes
D000081:Acetamides; D000928:Antidepressive Agents; D003577:Cytochrome P-450 Enzyme System; D044094:Receptors, Melatonin; D012702:Serotonin Antagonists; C084711:agomelatine; D009281:Naphthalenes