INTRODUCTION: The safety and tolerability profiles of antidepressants can often 
influence the treatment choices of clinicians treating major depressive 
disorder. The purpose of this investigation was to characterize the safety and 
tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in 
treating depression.
METHODS: An integrated analysis of all short-term, randomized, double-blind, 
placebo-controlled registration studies for major depressive disorder (four 
flexible-dose and five fixed-dose studies) was performed. Adult outpatients with 
major depressive disorder received desvenlafaxine doses ranging from 50-400 
mg/day or placebo for 8 weeks. Treatment-emergent adverse events, laboratory 
values, vital signs, and discontinuation symptoms were evaluated. In the subset 
of fixed-dose studies, dose-related effects were analyzed.
RESULTS: In the overall population (placebo: n=1,116; desvenlafaxine: n=1,834), 
adverse events resulted in discontinuations in 3% of placebo-treated patients 
and 12% of desvenlafaxine-treated patients; in the subset of fixed-dose studies, 
the rates were 4% with placebo and increased with desvenlafaxine dose (50 
mg/day: 4%; 400 mg/day: 18%). The most common treatment-emergent adverse event 
was transient nausea that was generally mild to moderate. The most common sexual 
dysfunction associated with desvenlafaxine treatment was erectile dysfunction in 
men (7% vs 1% with placebo) and anorgasmia in women (1% and 0%). One 
desvenlafaxine-treated patient died of a completed suicide; there were four 
suicide attempts (three desvenlafaxine, one placebo) and eight cases of suicidal 
ideation (five desvenlafaxine, three placebo) during the on-therapy period. 
Small but statistically significant changes in mean blood pressure occurred at 
all desvenlafaxine doses; clinically meaningful changes were observed in 1% of 
placebo-treated patients and 2% of desvenlafaxine-treated patients. 
Desvenlafaxine was associated with small but statistically significant mean 
changes in laboratory assessments, particularly lipid and liver enzyme 
elevations, and electrocardiograms; few cases of these changes were clinically 
relevant.
CONCLUSION: Desvenlafaxine in the treatment of major depressive disorder 
exhibited a safety and tolerability profile generally consistent with the 
serotonin-norepinephrine reuptake inhibitor class. The most common adverse event 
was transient nausea. At the recommended therapeutic dose of 50 mg/day, 
discontinuation due to adverse events was similar to placebo.