The primary aim of the present study was to compare the effects of agomelatine and venlafaxine XR on anhedonia in patients with Major Depressive Disorder. Secondary endpoints were to test its antidepressant and anxiolytic efficacy.

Sixty patients received randomly agomelatine (25–50 mg/day; N = 30) or venlafaxine XR (75-150 mg/day, N = 30). Psychopathological assessment was performed at baseline and over eight weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression (CGI).

Both groups showed an overall significant reduction in times for SHAPS, HAM-D and HAM-A. A significant difference between times was observed for SHAPS scores in Agomelatine group: from baseline of 6.5 (T0) to 4 at week 1 (−2.5) (T1), 3.5 at week 2 (−3.0) (T2), and 3.4 at week 8 (−2.9) (T3). In the venlafaxine group, the reduction on SHAPS scores was not significant between visits (p = .08). At the last observation a significant difference between groups in favour of agomelatine was observed for SHAPS scores (D = 2.2; p < 0.05); moreover, only patients treated with agomelatine showed a significant improvement in CGI scores from baseline (D = 2.94, p < 0.05).

Agomelatine showed significantly greater efficacy on anhedonia and at least similar antidepressant efficacy to venlafaxine in patients with Major Depressive Disorder, with a better clinical improvement. Therefore, the efficacy of agomelatine on anhedonia, a potential trait marker of vulnerability for depression, holds particular importance in the treatment of patients with depressive features.