Efficacy of the novel antidepressant agomelatine for anxiety symptoms in major depression

Objectives Anxiety in major depression is associated with increased morbidity. The antidepressant, agomelatine, which acts as an agonist at melatonin MT₁ and MT₂ receptors and as an antagonist at serotonin 5-HT_2C receptors, has demonstrated efficacy and safety in both major depression and generalized anxiety disorder. Here, we investigated the efficacy of agomelatine in anxious depression. Methods Data from three placebo-controlled short-term trials of agomelatine and three comparative studies of agomelatine versus fluoxetine, sertraline, and venlafaxine were pooled. Effects of agomelatine on anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale in four studies (one vs placebo and three vs active comparator) and with the Hamilton Depression Rating Scale (HAMD) anxiety subscore in all six studies. Anxiolytic and antidepressant efficacies of agomelatine were assessed in patients with more severe anxiety symptoms at baseline (score ≥5 on HAMD anxiety subscore). Results Agomelatine had a significantly greater effect on anxiety symptoms than both placebo and a number of comparator antidepressants. In more anxious depressed patients, agomelatine had a significantly greater effect on anxiety and depressive symptoms than both placebo and comparator antidepressants. Conclusion Once-a-day oral agomelatine is a new, efficacious alternative option for the treatment of anxiety in patients with major depression.