Agomelatine: efficacy at each phase of antidepressant treatment

Antidepressant pharmacotherapy forms the basis of management of major depressive disorder (MDD). In principle, the management of MDD should first elicit rapid relief of symptoms and then restore normal functioning and prevent relapse. It is recommended that treatment should continue for at least one year to minimize the risk of recurrence. Currently, most antidepressants fail to fulfill these goals, and rates of remission and long-term compliance are usually unsatisfactory. These shortcomings may be linked to tolerability and residual symptoms. Agomelatine is a novel antidepressant with an innovative mode of action characterized by agonism at the melatonergic MT(1)/MT(2) receptors and antagonism at the 5-HT(2C) receptors. As early as one week into treatment, depressive symptoms evaluated by the Clinical Global Impression Scale - Improvement (CGI-I) showed a significant improvement with agomelatine compared with venlafaxine (p < 0.0001). This rapid antidepressant efficacy was also seen at 2 weeks on the Hamilton Rating Scale for Depression (HAM-D), on which the mean total scores for agomelatine were lower than those for placebo (p < 0.05). At 6-8 weeks, evaluation on HAM-D, CGI-I and the CGI - Severity of illness (CGI-S) showed significant improvements with agomelatine versus placebo (p < 0.05). Patients treated with agomelatine also experienced greater relief of symptoms on CGI-I at 6 weeks compared with venlafaxine (p < 0.05). The antidepressant efficacy of agomelatine is maintained over the long term; almost 80% of patients remain free from relapse after 10 months of treatment. Agomelatine also significantly improves disturbed sleep and anxiety within depression, and this broad efficacy minimizes the risk of residual symptoms. The recent registration of agomelatine by the European Medicines Agency now offers the potential of fulfilling many currently unmet clinical needs throughout the time course of management of MDD.