P0031 - Pooled analysis of the safety and tolerability of desvenlafaxine Succinate compared with placebo in the treatment of major depressive disorder

Abstract

Objective:

To characterize the safety and tolerability of desvenlafaxine succinate (DVS) in patients with major depressive disorder (MDD).

Methods:

Pooled data from 7 double-blind, placebo-controlled studies were analyzed. Adult outpatients with DSM-IV MDD received DVS or placebo for 8 weeks. Four studies employed flexible dosing of DVS (100-200mg/d [1 study]; 200-400mg/d [3 studies]); 3 studies evaluated fixed doses (100/200/400mg/d [1 study]; 200/400mg/d [2 studies]). Vital signs and treatment-emergent adverse events (TEAEs) were evaluated. In the fixed-dose subset of studies, dose-related effects were analyzed.

Results:

The overall safety population consisted of 2014 patients (DVS: n=1211; placebo: n=803); 60% were women. Adverse events were responsible for discontinuations in 4% of placebo-treated patients and 15% of DVS-treated patients. Discontinuation rates increased with dose (10% with 100mg/d to 17% with 400mg/d) in the subset of fixed-dose studies. TEAEs were consistent with the serotonin-norepinephrine reuptake inhibitor (SNRI) class. Nausea was generally mild to moderate with a median duration less than or = to 6 days; the incidence decreased to placebo-like rates after week 1. With all doses of DVS, small but statistically significant changes in mean blood pressure were observed. Mean changes in pulse rate and the proportion of potentially clinically important increases in sustained elevations in supine diastolic blood pressure were higher for patients receiving 200/400mg/d than among placebo-treated subjects; values for these parameters with the 100mg/d dose did not differ from placebo.

Conclusions:

DVS treatment exhibited a safety and tolerability profile that was generally consistent with the SNRI class.