A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder

Abstract

The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.

Sexual Dysfunctions in Depression

“…The 5-HT2 blockade mechanism is thought to prevent serotonin-mediated adverse effects on sexual function. On the basis of this it is claimed that in comparison to SSRIs and ven afaxine, mirtazapine is significantly less likely to produce sexual dysfunction [34][35][36]. Ozmenler et al [37] also reported that when remitted patients with SSRI-induced sexual dysfunction were switched to mirtazapine, approximately half of them reported no sexual dysfunction at the end of the 8-week treatment.…”

Desvenlafaxine in the treatment of major depressive disorder

“…In the second trial by by Septien-Velez and colleagues, 31 375 patients were randomized to receive DVS 200 or 400 mg/day, or placebo. Patients assigned to the 400 mg/day dose, had a 1-week escalation period.…”

“…The initial dose fi nding trials examined doses of 100, 200 or 400 mg/day, [31][32][33] while subsequent trials evaluated daily doses of 50 and 100 mg. 34,35 Of 5 individual published clinical trials, 4 had a similar fi xed-dose design while 1 was a fl exible dose study.…”

“…Participants were also excluded if they had previously received treatment with DVS or venlafaxine within 90 days of the baseline. Three of the trials, in which the doses of DVS ranged from 100 to 400 mg/day, [31][32][33] excluded depressed patients with high levels of anxiety (defi ned as a Covi Anxiety Scale total score greater than 3 on any single item, a total score greater than 9, or a score greater than the Raskin Depression Scale total score). The length of the treatment for all the studies was 8 weeks, followed by one or 2 weeks of tapering, and a follow up visit 7 days after the last dose.…”

“…[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.…”