Agomelatine versus other antidepressive agents for major depression

Evidence Summaries

Level of Evidence = B
Agomelatine does not appear to provide a significant advantage in efficacy over other antidepressive agents in the acute-phase of major depression.

A Cochrane review 1 included 13 studies with a total of 4495 subjects with a major depressive disorder. The studies were conducted in both inpatient and outpatient settings. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs: paroxetine, fluoxetine, sertraline and escitalopram) and to the serotonin–norepinephrine reuptake inhibitor (SNRI: venlafaxine). Participants were followed up for 6 to 12 weeks. For the primary outcome, response to treatment, agomelatine did not differ from other SSRIs (RR 1.01, 95% CI 0.95 to 1.08; 10 trials, n=3826) or venlafaxine (RR 1.06; 95% CI 0.98 to 1.16; 3 trials, n=669). For remission, agomelatine did not differ from other SSRIs (RR 0.83; 95% CI 0.68 to 1.01; 10 trials, n=3826), or venlafaxine (RR 1.08; 95% CI 0.94 to 1.24; 3 trials, n=669). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67; 2 trials, n=392), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09; 10 trials, n=3826). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, 1 trial, n=322).

Comment: The quality of the evidence is downgraded by indirectness of evidence (short follow-up time).


1. Guaiana G, Gupta S, Chiodo D et al. Agomelatine versus other antidepressive agents for major depression. Cochrane Database Syst Rev 2013;12():CD008851.  [PMID:24343836]
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