Agomelatine: The evidence for its place in the treatment of depression

Depressive disorders are among the main causes of disability due to disease. In spite of recent progress in the pharmacotherapy of depression, there is still a high nonresponse rate of approximately 30% to the first antidepressant treatment. Furthermore, the latency of several weeks until sufficient clinical improvement and the risk of side effects remain unresolved problems. Therefore, there is still further need for the development of new antidepressants. In the last years a variety of melatonin receptor agonists have been synthesized and evaluated for the treatment of sleep disorders. Animal studies suggested that agomelatine (S-20098), a synthetic melatonergic MT(1) and MT(2) receptor agonist with serotonin receptor antagonistic properties, may have additional activating properties and may represent a new approach in the treatment of depression.

Clinical trials that have demonstrated efficacy and safety of agomelatine for the treatment of depression are reviewed.

In clinical trials, including phase III studies, superior efficacy compared to placebo and good efficacy compared to standard antidepressants was shown for agomelatine for the acute treatment of major depression. In all studies published so far agomelatine was safe and the overall tolerability profile was superior to selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors.

Agomelatine may represent a novel perspective in the treatment of acute depression. The improvement of sleep disturbances, the tolerability in terms of sexual side effects, and the lack of withdrawal symptoms after abrupt discontinuation of treatment may represent important clinical benefits compared to established antidepressants.