Early response to trazodone once-A-day in major depressive disorder: Review of the clinical data and putative mechanism for faster onset of action

Background Most antidepressants have a delayed onset of action and must be administered for several weeks to generate therapeutic effects. Trazodone is a serotonin antagonist and reuptake inhibitor approved for the treatment of major depressive disorder. The once-A-day (OAD) formulation of trazodone has an improved tolerability profile compared to its conventional formulations. In this study, we systematically reviewed the evidence available for the antidepressant efficacy and early improvement in depressive symptoms with trazodone OAD treatment. Method We conducted a PubMed database search for randomized controlled trials published from 2005 to 2020. Results Two studies, a placebo-controlled and an active-comparator (venlafaxine extended-release or XR) study were found. Both the studies demonstrated that trazodone exhibits antidepressant activity at a starting dose of 150Â mg/day and results in statistically significant greater reduction in Hamilton Depression Rating Scale (HAM-D17) scores within 1Â week of starting treatment compared to placebo or venlafaxine XR (PÂ