Efficacy and tolerance profile of agomelatine and practical use in depressed patients.

Agomelatine is a new agent with a unique pharmacological profile, as the first melatonergic antidepressant. Its antidepressant efficacy has been demonstrated in the treatment of major depressive disorder (MDD) at a dose of 25 mg/day. Expectations from antidepressant therapies now go beyond efficacy alone, to include advantages in tolerability and safety. Due to its pharmacological profile, agomelatine does not induce the side-effects typical of other therapies, such as selective serotonin reuptake inhibitors (i.e. gastrointestinal disorders, weight gain, serotonergic syndrome and insomnia). Moreover, a placebo-controlled trial in MDD comparing the effects of agomelatine and venlafaxine on sexual dysfunction (another significant side-effect with current antidepressant medications) indicated the very favourable profile of agomelatine; in the same study, there was similar antidepressant efficacy in the same two groups. A double-blind, placebo-controlled trial investigating the effect of abrupt cessation of treatment demonstrated the absence of discontinuation symptoms with agomelatine, which was in contrast with the results observed with paroxetine. The ability of an antidepressant to relieve sleep complaints with no sedative effects is a key advantage because sleep complaints are a major presenting feature of depression. Again due to its unique pharmacological profile, agomelatine has been shown to positively influence disturbed circadian rhythms in depressed patients by significantly improving all phases of disturbed sleep and the overall quality of sleep, with a favourable impact on daytime alertness. In conclusion, experience with agomelatine across a range of clinical studies suggests that this compound offers a novel approach to the treatment of depression combining efficacy, even in severe depression, with an extremely favourable side-effect profile and sleep regulation. These properties give agomelatine a definite clinical advantage in the treatment of depression.