Efficacy and safety of desvenlafaxine 25 and 50▒mg/day in a randomized, placebo-controlled study of depressed outpatients.

Background: This study evaluated the efficacy and safety of low-dose desvenlafaxine (administered as desvenlafaxine succinate) in treating major depressive disorder (MDD).

Methods: Adult outpatients (aged 18 years) in the United States and (aged 20 years) in Japan, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for MDD and had a 17-item Hamilton Depression Rating Scale (HAM-D17) score 20, were ran-domly assigned to placebo, low-dose desvenlafaxine (25▒mg/day), or the recommended dose (50▒mg/day) after a 6to 14-day placebo lead-in, in an 8-week, fixed-dose trial. The primary efficacy variable was change from baseline in HAMD17 total score at final on-therapy evaluation. Efficacy analyses were based on the intent-totreat (ITT) population, using the last observation carried forward.

Results: The ITT population included 699 patients. Reduction in HAM-D17 scores from baseline to final evaluation was not significantly greater for desvenlafaxine 25▒mg/day (-8.98) but was significantly greater for desvenlafaxine 50▒mg/day (-10.02; P = 0.016) versus placebo (-8.52) after adjusting for multiplicity. P-values were < 0.05 versus placebo for percentage of patients responding to treatment ( 50% decrease in HAM-D17 score) with desven-lafaxine 50▒mg/day (46%; P = 0.015), but not with desvenlafaxine 25▒mg/day (42% versus 35% with placebo). P-values for remission rates (HAM-D17 score ≤ 7) were not < 0.05 versus placebo for either desvenlafaxine treatment group. Discontinuations due to adverse events were observed in 2.6%, 3.4%, and 3.4% of patients treated with placebo, desvenlafaxine 25▒mg/day, and desvenlafaxine 50▒mg/day, respectively.

Conclusions: Consistent with other clinical studies, desvenlafaxine 50▒mg/day demonstrated antidepressant efficacy and appears to be the minimally effective dosage for MDD. ClinicalTrials study identifier NCT00798707.