Efficacy of Desvenlafaxine 50 mg/d Versus Placebo in the Long-Term Treatment of Major Depressive Disorder: A Randomized, Double-Blind Trial

Abstract

Objective: To examine long-term (11-month) antidepressant efficacy of desvenlafaxine 50 mg/d across a broad range of clinical and functional outcomes in patients with major depressive disorder.

Method: Adult outpatients (≥ 18 years) with major depressive disorder (DSM-IV criteria) and a 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 20 at screening and baseline who responded to 8 weeks of open-label desvenlafaxine 50 mg/d and had a continuing stable response through week 20 were randomly assigned to receive placebo or desvenlafaxine 50 mg/d in a 6-month, double-blind, randomized withdrawal period. Depressive symptoms were evaluated using the HDRS-17, 6-item HDRS, and Clinical Global Impressions-Severity of Ilness and -Improvement (CGI-S, CGI-I). Health outcomes included the Work Productivity and Activity Impairment (WPAI) questionnaire and the World Health Organization 5-Item Well-Being Index (WHO-5). The trial was conducted from June 2009 to March 2011 at 87 study sites in 14 countries worldwide.

Results: Of 874 patients enrolled in open-label treatment, 548 patients were randomly assigned to receive double-blind placebo (n = 276) or desvenlafaxine 50 mg/d (n = 272). At the end of the 6-month double-blind treatment, improvements in depressive symptoms were better maintained among the desvenlafaxine- than placebo-treated patients on all efficacy endpoints (all P ≤ .001); in the desvenlafaxine group, 21.8% (vs 42.9% in the placebo group) had CGI-I ratings of 5, 6, and 7 (minimally worse/much worse/very much worse), and 74.4% met criteria for remission (placebo: 54.2%). WPAI and WHO-5 scores indicated significantly better productivity and well-being with continued desvenlafaxine (vs placebo, P ≤ .001).

Conclusions: Long-term treatment with desvenlafaxine 50 mg/d maintained improvements in major depressive disorder among adult outpatients who exhibited a stable therapeutic response.

Trial registration: ClinicalTrials.gov identifier: NCT00887224.

Figures

Figure 1.

Patient Flowcharta aReprinted with permission from Rosenthal et al. bSum of reasons for screen failure is greater than total screen failures because patients may have had multiple reasons.

Figure 2.

Mean HDRS-17 Total Score: All-Enrolled (response and stability phases, LOCF) and All-Randomized (double-blind period, MMRM) Populations Abbreviations: HDRS-17 = 17-item Hamilton Depression Rating Scale, LOCF = last observation carried forward, MMRM = mixed-effects model for repeated measures.

Figure 3.

CGI-I Scores at Double-Blind Week 26 (LOCF)a aEvaluation of improvement for the CGI-I was based on comparison against status at randomization to double-blind treatment. Improvement was rated as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse). Cochran-Mantel-Haenszel test for desvenlafaxine versus placebo, P < .001. Abbreviations: CGI-I = Clinical Global Impressions–Improvement, LOCF = last observation carried forward.