BACKGROUND: In an effort to establish the lowest effective dose of 
desvenlafaxine (administered as desvenlafaxine succinate), we assessed the 
efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs 
placebo for the treatment of major depressive disorder.
METHODS: Adult outpatients with DSM-IV-defined major depressive disorder and a 
17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score ≥20 were 
randomly assigned to receive placebo or desvenlafaxine (10 or 50 mg/day) after a 
6- to 14-day single-blind placebo lead-in period in an 8-week, phase 3, 
fixed-dose trial. The primary efficacy measure was change from baseline in the 
HAM-D(17) score analyzed using analysis of covariance. Efficacy analyses were 
conducted with the intent-to-treat population, using the last observation 
carried forward.
RESULTS: The intent-to-treat population included 673 patients. Change from 
baseline to final evaluation in adjusted HAM-D(17) total scores was not 
significantly different comparing desvenlafaxine 10 mg/day (-9.28) and 
desvenlafaxine 50 mg/day (-8.92) with placebo (-8.42). There were no differences 
among treatment groups in the rates of treatment response or remission. 
Discontinuations due to adverse events occurred in 1.8%, 0.9%, and 1.8% of 
patients in the placebo and desvenlafaxine 10- and 50-mg/day groups, 
respectively. Overall rates of treatment-emergent adverse events with both doses 
were similar to placebo.
CONCLUSIONS: Both doses of desvenlafaxine failed to separate from placebo. 
However, in a companion study reported separately, desvenlafaxine 50 mg, but not 
25 mg, separated from placebo. Taken together, these studies suggest that 50 mg 
is the minimum effective dose of desvenlafaxine for the treatment of major 
depressive disorder. CLINICALTRIALS.GOV IDENTIFIER: NCT00863798 
http://clinicaltrials.gov/ct2/show/NCT00863798?term=00863798&rank=1.