Agomelatine is a new antidepressant with an unique pharmacological profile. It is a potent agonist of melatonin receptors (MT1 and MT2) and also an antagonist at 5-HT2C receptors Agomelatine's acute efficacy in treating MDD was seen in three placebo-controlled studies, including a dose-ranging study with paroxetine as active comparator.

The meta-analysis of these trials showed a significant difference between agomelatine and placebo in the main efficacy analysis, the HAMD score (= 2.86 0.56; P<0.001) and in the CGI scale (=0.47 0.10; P<0.001).

Furthermore, evidence of agomelatine's efficacy in severe depression was illustrated by the meta-analysis of the patient subgroup with a baseline HAMD 25. Analysis of pooled data demonstrated an increase in the magnitude of the agomelatine-placebo difference with increasing severity at baseline.

The antidepressant efficacy of agomelatine was also evaluated in direct comparison to venlafaxine in 2 trials. Agomelatine showed at least comparable efficacy to venlafaxine in depressed patients after 6 and 12 weeks of treatment.

Agomelatine did not show the typical side effects found with selective serotonin reuptake inhibitors (SSRIs) (ie, gastrointestinal disorders, weight gain, serotonergic syndrome, and insomnia).

Moreover, agomelatine was shown to lack discontinuation symptoms compared with placebo in a study showing significant discontinuation symptoms with paroxetine.

In conclusion, the experience with agomelatine across a wide range of clinical trials suggests that agomelatine offers an important alternative for the treatment of depression, combining efficacy, even in the most severely depressed patients, with a favourable side-effect profile.