OBJECTIVE: To assess the efficacy, safety, and tolerability of 50- and 
100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a 
serotonin-norepinephrine reuptake inhibitor, for the treatment of major 
depressive disorder (MDD).
RESEARCH DESIGN AND METHODS: Patients with Diagnostic and Statistical Manual of 
Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale 
for Depression (HAM-D(17)) scores > or =20 were randomly assigned to 
double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 
mg/day) for 8 weeks. The primary efficacy measure was the HAM-D(17). Changes 
from baseline in HAM-D(17) scores were analyzed using analysis of covariance. 
The final on-therapy evaluation was the primary endpoint for efficacy analyses, 
using last-observation-carried-forward data. MAIN OUTCOMES MEASURES AND RESULTS: 
The intent-to-treat population included 447 patients. Desvenlafaxine 50 mg was 
associated with a significantly greater adjusted mean change from baseline on 
the HAM-D(17) (-11.5) compared with placebo (-9.5, p=0.018); the 100-mg dose 
group (-11.0) did not achieve statistical significance (p=0.065). The 100-mg 
dose group experienced significant improvements compared with placebo on several 
secondary efficacy measures, including the 6-item Hamilton Depression Rating 
Scale (p=0.038) and the Visual Analog Scale-Pain Intensity total score 
(p=0.041). Both desvenlafaxine doses were generally well-tolerated. The most 
common adverse events (incidence > or =10% in either desvenlafaxine group and 
twice the rate of placebo) were dry mouth, constipation, insomnia, decreased 
appetite, hyperhidrosis, and dizziness.
CONCLUSIONS: These results demonstrate efficacy, safety, and tolerability of 
desvenlafaxine 50 mg/day for treating MDD. The significant findings on secondary 
measures support the efficacy of desvenlafaxine 100 mg, as seen in other trials. 
Conclusions may be limited by the exclusion of MDD patients with comorbid 
conditions and the short-term desvenlafaxine treatment duration.