A pooled analysis of two placebo-controlled trials of desvenlafaxine in major depressive disorder

Abstract

The efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) were evaluated in two similarly designed, phase 3, randomized, double-blind, placebo-controlled, venlafaxine-extended-release-referenced, flexible-dose studies of outpatients with a primary diagnosis of major depressive disorder. Owing to a high placebo response, the individual studies were underpowered. Therefore, a post-hoc pooled analysis was performed (desvenlafaxine and placebo data were pooled; venlafaxine extended release data were not, owing to different flexible-dose regimens in the two studies). The primary outcome measure was the change from baseline on the 17-item Hamilton Rating Scale for Depression; the Clinical Global Impressions-Improvement item score was a secondary outcome. Analysis of the pooled data (using a mixed-effect model for repeated measures) revealed that after 8 weeks of treatment, desvenlafaxine was significantly better than placebo on 17-item Hamilton Rating Scale for Depression [-14.21 vs. -11.87 for desvenlafaxine and placebo, respectively; magnitude of effect=-2.34 (P<0.001)] and Clinical Global Impressions-Improvement item scores [1.95 vs. 2.32 for desvenlafaxine and placebo, respectively; magnitude of effect=-0.37 (P<0.001)]. Adverse events were comparable to those found with other drugs sharing a similar mechanism of action. These data support the efficacy, safety, and tolerability of desvenlafaxine in the treatment of major depressive disorder.

Desvenlafaxine in the treatment of major depressive disorder

“…Mean decreases in weight for DVS treatment groups were statistically signifi cant compared with baseline and placebo in both high and low dose trials. [31][32][33][34][35][36] In the DVS 400 mg group, there was a statistically signifi cant decrease in weight compared to the DVS 100 mg and 200 mg groups. Data pooled from 7 clinical trials, showed that treatment with DVS was associated with small mean decreases in weight in the short term (1 kg), which persisted up to 6 months with a small mean increase (Ͻ1 kg) and was comparable to placebo.…”

“…The number of completers in the DVS group (72%) was lower than in either venlafaxine ER group (75-150 mg/day: 85%; 150-225 mg/day: 77%) or placebo (86%) in the pooled analysis. 36 Nausea was the most common reason cited for discontinuation among DVS patients in all studies, except for one study with DVS 200 mg (fl exible dose) 33 where insomnia (3%) was the most frequent reason for discontinuation.…”

“…36 Each was a negative trial for DVS, but assay sensitivity was confi rmed in the venlafaxine group. Data on DVS from both studies were pooled post hoc, and yielded positive results.…”

“…31,32,33 Nausea was higher in the DVS (200 and 400 mg/day) groups (38%) compared to both venlafaxine groups (75-150 mg/day: 21%; 150-225 mg/day: 29%). 36 The most frequently reported TEAEs other than nausea were: insomnia, somnolence, dry mouth, dizziness, sweating, nervousness, anorexia, constipation, asthenia, and sexual dysfunction ( Table 1).…”

“…[31][32][33][34][35][36] Several published abstracts were also reviewed: including a fl exible dose trial of DVS 200 to 400 mg, 37 a trial comparing DVS 50 and 100 mg to placebo with a duloxetine reference arm, 8 as well as two unpublished pooled analyses, the fi rst involving 7 short-term trials with DVS doses between 100 and 400 mg 39 and the second from 2 trials with DVS at 50 and 100 mg. 40 Other studies of DVS as a treatment for vasomotor symptoms of menopause and pain were not reviewed. No published trials for generalized anxiety disorder or other anxiety disorders were located.…”