A placebo-controlled study evaluating the efficacy and safety of flexible-dose desvenlafaxine treatment in outpatients with major depressive disorder.

Introduction: This research compares the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) versus placebo in treating major depressive disorder.

Methods: In this randomized, double-blind study, outpatients with major depressive disorder > or =18 years of age received desvenlafaxine 200-400 mg/day or placebo for 8 weeks. Efficacy endpoints included (primary) change in 17-item Hamilton Rating Scale for Depression score at the final evaluation (last observation carried forward, analysis of covariance) and (secondary) Clinical Global Impressions-Improvement and -Severity of Illness scales.

Results: The difference between desvenlafaxine (n==) and placebo (n==) on the primary endpoint was not significant (-9.1 vs -7.5, P=.078). Week 8 observed cases (desvenlafaxine, n=80; placebo, n=94) results were significant (-10.7 vs -7.9, P=.008). Differences at the final evaluation (last observation carried forward) were significant for Clinical Global Impressions-Improvement (2.9 vs 2.5, P=.037) and Clinical Global Impressions-Severity of Illness (-1.9 vs -1.2, P=.041). Discontinuation rates due to adverse events (AEs) were 12% and 3% for desvenlafaxine and placebo, respectively (P=.008). The most frequently reported AE associated with desvenlafaxine was nausea (36% vs 9% [placebo]).

Conclusion: In this study, the primary analysis did not show significant differences between desvenlafaxine and placebo; discontinuations due to AEs associated with the desvenlafaxine dose range may have contributed to the lack of statistical separation.