Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial

Abstract

The objective of this study was to assess the efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) 50 and 100 mg/day for major depressive disorder (MDD). A multicenter, randomized, double-blind, placebo-controlled trial was conducted in Europe and South Africa. Outpatients with MDD received fixed-dose desvenlafaxine (50 or 100 mg/day) or placebo for 8 weeks. The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression total score; secondary measures included Clinical Global Impressions-Improvement scores. The intent-to-treat population included 483 patients: desvenlafaxine 50 mg (n=164), desvenlafaxine 100 mg (n=158), and placebo (n=161). At the last-observation-carried-forward analysis (final evaluation) using analysis of covariance, adjusted mean changes from baseline on the Hamilton Rating Scale for Depression were significantly greater for both desvenlafaxine 50 mg (-13.2; P=0.002) and 100 mg (-13.7; P<0.001) versus placebo (-10.7). Significant differences on the Clinical Global Impressions-Improvement scores were observed for desvenlafaxine 50 mg (P=0.002) and 100 mg (P<0.001) versus placebo. Both doses of desvenlafaxine were generally well tolerated. The most common treatment-emergent adverse events were nausea, dizziness, insomnia, constipation, fatigue, anxiety, and decreased appetite. Fixed doses of desvenlafaxine 50 and 100 mg/day are safe, generally well tolerated, and effective at a clinically relevant level for the treatment of MDD.

Effect of Food on the Pharmacokinetics of Desvenlafaxine in Healthy Subjects

“…Studies investigating desvenlafaxine at lower doses (ie, 50 and 100 mg/d) have demonstrated better tolerability and lower occurrences of AEs [14,15,20].…”

“…Clinical trials of desvenlafaxine administration in healthy adults [13] and in patients with MDD [14,15] have also demonstrated sustainedrelease characteristics that support once-daily administration. For clinical use, it is important to determine if the type of food intake affects pharmacokinetic behavior, as variability could result in unpredictable clinical effects and might necessitate specific dosing guidelines.…”

“…At the time the study was designed and conducted, 200 mg was believed to be the upper range of therapeutic doses that would be available in clinical practice. However, the results of subsequent clinical trials [14,15] demonstrated that the optimal dose was considerably lower, and 50 mg is now the recommended daily therapeutic dose for MDD in the United States.…”

Desvenlafaxine in the treatment of major depressive disorder

“…[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.…”

Is the antidepressive effect of second-generation antidepressants a myth?

“…However, in the placebo-controlled trial with desvenlafaxine, the latest antidepressant approved by FDA (Young & Plosker, 2008), the mean drug-placebo improvement score on HAMD was assumed to be 3.0 and the pooled standard deviation 8.0, resulting in an expected effect size of 0.38 (Boyer et al 2008).…”