+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies



Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies



Clinical Therapeutics 31 Pt 1: 1405-1423



Major depressive disorder (MDD) is a common, chronic illness associated with substantial disability and economic burden. Although a number of effective antidepressants are available, the need for new medications that are effective and well tolerated remains. The aim of this study was to compare the efficacy and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/d with placebo for MDD. A post hoc pooled analysis was conducted to evaluate this study in the context of all similarly designed, completed studies with the 2 doses. This was an 8-week, Phase III, randomized, double-blind, duloxetine-referenced, placebo-controlled, parallel-group trial conducted in 21 centers across the United States. Duloxetine was included for assay sensitivity as a positive control; the study was not designed or powered to compare desvenlafaxine with duloxetine. Participants were outpatients aged > or =18 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined MDD and a 17-item Hamilton Rating Scale for Depression (HAM-D(17)) score > or =20. Patients were randomly assigned at baseline to fixed-dose desvenlafaxine (50 or 100 mg/d), fixed-dose duloxetine (60 mg/d), or placebo. The primary outcome measure was HAM-D(17) total score at the final evaluation. Additional measures included the Clinical Global Impressions-Improvement (CGI-I) score, Montgomery Asberg Depression Rating Scale (MADRS) score, Clinical Global Impressions-Severity (CGI-S) score, and 6-item Hamilton Rating Scale for Depression, Bech version (HAM-D(6)). Tolerability assessments included discontinuation rates, adverse events (AEs), vital signs, and laboratory tests. The post hoc pooled analysis was performed using data from the current study and 2 previously published, positive studies that compared the efficacy and tolerability of desvenlafaxine 50 and 100 mg/d with placebo for MDD. The design and methodologies of the 2 studies were similar to the methodology of the current trial, other than not including a reference compound. Of the 925 patients who were screened, 287 did not meet entry criteria, and 638 patients enrolled in the study; the intent-to-treat (ITT) population included 615 patients who were evaluated for efficacy (mean [SD] age range, 38.8-40.7 [12.1-13.2] years; mean weight range, 83.3-87.0 [22.8-23.9] kg; female sex, 398 [64.7%]; white race, 458 [74.5%]). The primary end point did not reach significance based on the global F test for controlling multiplicity of the desvenlafaxine doses. Based on pairwise comparison, significantly greater improvements on the HAM-D(17) were observed in the desven-lafaxine 100 mg/d (-10.5; P = 0.028, unadjusted for multiple comparisons) and duloxetine 60 mg/d groups (-10.3; P = 0.047) compared with placebo (-8.7). Desvenlafaxine 100 mg/d and duloxetine 60 mg/d were associated with significantly better scores compared with placebo on the CGI-I, MADRS, CGI-S, and HAM-D(6). No significant differences were observed in any scale between the desvenlafaxine 50 mg/d and placebo groups. Discontinuation rates due to AEs were 5%, 7%, 13%, and 6% for the desvenlafaxine 50-mg/d, desvenlafaxine 100-mg/d, duloxetine 60-mg/d, and placebo groups, respectively. The ITT population from all 3 studies in the pooled analysis consisted of 1388 patients (mean [SD] age range, 38.8-45.7 [12.1-12.6] years; mean weight range, 73.1-87.0 [17.6-23.9] kg; female sex, 896 [64.6%]; white race, 1136 [81.8%]). Significantly greater improvements on the HAM-D(17) were observed for desvenlafaxine 50 mg/d (-11.5; P < 0.001) and 100 mg/d (-11.8; P < 0.001) versus placebo (-9.6). Both doses were significantly better than placebo on the CGI-I, MADRS, and HAM-D(6). The current study failed to meet its primary efficacy end point based on the a priori analysis plan. Desvenlafaxine was generally well tolerated. A post hoc pooled analysis of this trial and 2 previously published trials with both desvenlafaxine 50 and 100 mg/d found both doses to be effective for MDD compared with placebo. ClinicalTrials.gov Identifier: 00384033.

(PDF emailed within 0-6 h: $19.90)

Accession: 052512475

Download citation: RISBibTeXText

PMID: 19698901

DOI: 10.1016/j.clinthera.2009.07.006


Related references

Desvenlafaxine compared with placebo for treatment of menopausal vasomotor symptoms: a 12-week, multicenter, parallel-group, randomized, double-blind, placebo-controlled efficacy trial. Menopause 20(1): 28-37, 2013

Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate or severe major depressive disorder: a pooled analysis of six randomized, double-blind, placebo-controlled studies. International Clinical Psychopharmacology 28(6): 312-321, 2014

A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. International Clinical Psychopharmacology 22(6): 338-347, 2007

Assessing the efficacy of desvenlafaxine for improving functioning and well-being outcome measures in patients with major depressive disorder: a pooled analysis of 9 double-blind, placebo-controlled, 8-week clinical trials. Journal of Clinical Psychiatry 70(10): 1365-1371, 2009

Psychomotor symptoms and treatment outcomes of ziprasidone monotherapy in patients with major depressive disorder: a 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial. International Clinical Psychopharmacology 29(6): 332-338, 2015

A 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial of ziprasidone as monotherapy for major depressive disorder. Journal of Clinical Psychiatry 73(12): 1541-1547, 2013

A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. Journal of Clinical Psychiatry 68(11): 1663-1672, 2007

Analysis of the effect of desvenlafaxine on anxiety symptoms associated with major depressive disorder: pooled data from 9 short-term, double-blind, placebo-controlled trials. Cns Spectrums 15(3): 187-193, 2010

The effect of desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder: a substudy of a randomized, double-blind, placebo-controlled trial. Journal of Psychopharmacology 30(6): 559-567, 2018

Efficacy and safety of agomelatine in the treatment of major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychopharmacology 30(2): 135-144, 2011

Paroxetine treatment in children and adolescents with major depressive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry 45(6): 709-719, 2006

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies. International Clinical Psychopharmacology 27(1): 27-39, 2012

Desvenlafaxine 50 and 100 mg/d versus placebo for the treatment of major depressive disorder: a phase 4, randomized controlled trial. Journal of Clinical Psychiatry 76(5): 562-569, 2015

Efficacy of Desvenlafaxine 50 mg/d Versus Placebo in the Long-Term Treatment of Major Depressive Disorder: A Randomized, Double-Blind Trial. Primary Care Companion for Cns Disorders 17(4), 2015

Efficacy of Sertraline in Patients With Major Depressive Disorder Naive to Selective Serotonin Reuptake Inhibitors: A 10-Week Randomized, Multicenter, Placebo-Controlled, Double-Blind, Academic Clinical Trial. Journal of Clinical Psychopharmacology 38(5): 454-459, 2018