Trazodone once-a-day (OAD) and venlafaxine extended-release (XR) are effective antidepressants in patients with moderate-to-severe major depressive disorder (MDD), according to a study published in International Clinical Psychopharmacology.

In this active-controlled, double-blind, parallel-group study, patients with MDD (N=324) from 31 study centers across Europe were randomized to receive either venlafaxine XR 75 mg/once daily (n=158) or trazodone OAD 300 mg/day (n=166) for 8 weeks. After 3 and 5 weeks of treatment, the dose was increased by increments of 75 mg/day up to 225 mg/day venlafaxine XR and 450 mg/day trazodone OAD in nonresponding patients. Patients receiving increased dosages were strictly monitored for safety with follow-up visits up to 10 weeks. The primary endpoint for clinical efficacy was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D).

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There were reductions in mean HAM-D-17 total scores at the final visit compared with baseline (intent-to-treat [ITT]: trazodone, -12.9±6.82; venlafaxine, -14.7±6.56; 95% CI, 1.6 (0.4-2.9); P =.01) and (per protocol [PP]: trazodone, -15.4±5.32, venlafaxine, -16.4±5.39; 95% CI, 1.1 (0.0 to 2.2); P =.056). The PP treatment showed the best efficacy outcomes in both groups. Researchers observed an earlier onset of action with trazodone OAD compared with venlafaxine XR, with a significantly higher reduction in mean HAM-D-17 score after only 7 days in patients treated with trazodone OAD.

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This study was limited by the lack of a placebo control. However, the results confirmed evidence from a comprehensive review of the literature that venlafaxine can be considered among the most effective antidepressants and also reproduced the efficacy and safety of trazodone, particularly the early onset of action and positive effect on sleep disturbance.

“Since compliance and treatment adherence are crucial aspects of the outcome of MDD treatment, an early onset of antidepressant action is clinically important. Indeed, antidepressants that lead to a rapid improvement of depressive symptoms within a few days, and whose effects are sustained in time, would have an important impact on public health and on the life of MDD patients,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Fagiolini A, Albert U, Ferrando L, et al. A randomized, double-blind study comparing the efficacy and safety of trazodone once-a-day and venlafaxine extended-release for the treatment of patients with major depressive disorder [published online January 15, 2020]. Int Clin Psychopharmacol. doi: 10.1097/YIC.0000000000000304