Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial

The objective of this study was to assess the efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) 50 and 100 mg/day for major depressive disorder (MDD). A multicenter, randomized, double-blind, placebo-controlled trial was conducted in Europe and South Africa. Outpatients with MDD received fixed-close desvenlafaxine (50 or 100 mg/day) or placebo for 8 weeks. The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression total score; secondary measures included Clinical Global Impressions-improvement scores. The intent-to-treat population included 483 patients: desvenlafaxine 50mg (n = 164), desvenlafaxine 100 mg (n = 158), and placebo n = 161). At the last-observation-carried-forward analysis (final evaluation) using analysis of covariance, adjusted mean changes from baseline on the Hamilton Rating Scale for Depression were significantly greater for both desvenlafaxine 50 mg (-13.2; P = 0.002) and 100 mg (-13.7; P < 0.001) versus placebo (-10.7). Significant differences on the Clinical Global Impressions-Improvement scores were observed for desvenlafaxine 50 mg (P = 0.002) and 100 mg (P < 0.001) versus placebo. Both doses of desvenlafaxine were generally well tolerated. The most common treatment-emergent adverse events were nausea, dizziness, insomnia, constipation, fatigue, anxiety, and decreased appetite. Fixed doses of desvenlafaxine 50 and 100 mg/day are safe, generally well tolerated, and effective at a clinically relevant level for the treatment of MDD.