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
ABSTRACT To evaluate the effects of desvenlafaxine therapy on functioning and well-being in major depressive disorder (MDD).
Total and individual item Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5) scores from 8 double-blind, placebo-controlled, 8-week desvenlafaxine clinical trials were pooled. Scores on the 17-item Hamilton Depression Rating Scale (HDRS(17)) work/activities and Montgomery-Asberg Depression Rating Scale (MADRS) lassitude items were pooled from 9 studies. Outpatients with DSM-IV MDD were randomly assigned to fixed (5 studies; 50, 100, 200, or 400 mg/d; n = 1,342) or flexible (4 studies, 100-400 mg/d; n = 463) doses of desvenlafaxine or placebo (n = 1,108). Data from each patient's final evaluation were analyzed for the total population and for individual dose groups from the fixed-dose studies and were compared between groups using analysis of covariance.
Compared with placebo, desvenlafaxine therapy resulted in significantly greater improvements in SDS total score (-2.0) and individual items regarding work (-0.6), social life/leisure activities (-0.8), and family life/home responsibilities (-0.7; P < .001 for all comparisons), as well as WHO-5 total score (1.7) and individual items (good spirits [0.4], calm/relaxed [0.4], active/vigorous [0.3], fresh/rested [0.3], and interest [0.3]; P < .001 for all comparisons). Desvenlafaxine treatment resulted in significant improvements on the HDRS(17) work/activities (-0.2; P < .001) and MADRS lassitude (-0.3; P < .001) items compared with placebo. Significant differences were observed for the individual fixed-dose groups on all outcomes (P < .05); there was no evidence of a dose-response relationship.
Desvenlafaxine therapy resulted in significant improvements in the functioning and well-being among MDD patients.
- SourceAvailable from: Narong ManeetonMental Illnesses - Evaluation, Treatments and Implications, 01/2012; , ISBN: 978-953-307-645-4
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ABSTRACT: This is the first study to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for improving depressive symptoms and functioning exclusively in employed patients with major depressive disorder (MDD). Gainfully employed (≥20 h/wk) male and female outpatients with MDD were randomly assigned (2:1 ratio) to 12 weeks of double-blind treatment with desvenlafaxine 50 mg/d or placebo. Analysis of covariance was used to compare differences in week 12 adjusted mean changes from baseline on the 17-item Hamilton Depression Rating Scale (HAM-D₁₇) (primary outcome) and Sheehan Disability Scale (SDS) (key secondary outcome) in the intent-to-treat (ITT) population. A predefined, modified ITT population (ie, those in the ITT population with baseline HAM-D₁₇ ≥20) was also analyzed. Tolerability was assessed by recording adverse events and change on the Arizona Sexual Experience Scale. Baseline HAM-D₁₇ scores for desvenlafaxine (n = 285) and placebo (n = 142) were 22.0 and 21.8, whereas baseline SDS scores were 19.8 and 20.4. Adjusted mean differences between desvenlafaxine and placebo were 2.1 (95% confidence interval [CI], 0.78-3.46; P = 0.002) on the HAM-D₁₇ and 1.3 (95% CI, -0.09 to 2.76; P = 0.067) on the SDS. For the modified ITT sample, desvenlafaxine (n = 208) and placebo (n = 102), baseline HAM-D₁₇ scores were 23.8 and 23.9; the SDS baseline scores were 20.1 and 20.8. Mean differences were 2.6 (95% CI, 0.93-4.22; P = 0.002) on the HAM-D₁₇ and 2.1 (95% CI, 0.36-3.76; P = 0.017) on the SDS. Adverse events and Arizona Sexual Experience Scale scores were comparable between groups. Desvenlafaxine 50 mg/d was efficacious for treating MDD in gainfully employed adults. Between-group differences on the SDS narrowly missed statistical significance in the ITT population alone, but the totality of data suggests functional improvements with active treatment.Journal of clinical psychopharmacology 08/2011; 31(5):569-76. DOI:10.1097/JCP.0b013e31822c0a68 · 3.76 Impact Factor
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ABSTRACT: The objective of this study was to explore the relationship between assessments of functional impairment, emotional well-being, and depression symptoms. Data were pooled from 3530 outpatients with major depressive disorder enrolled in 10 desvenlafaxine clinical trials. The primary outcome measures included (a) the 17-item Hamilton Rating Scale for Depression (HAM-D17) as a measure of depressive symptom severity and (b) the Sheehan Disability Scale (SDS) and five-item World Health Organization Well-Being Index (WHO-5) as measures of functional impairment and well-being. A linear regression model was used to identify the SDS and WHO-5 values that equate to the predetermined clinically relevant three-point difference between active treatment and placebo on the HAM-D17. A receiver operating characteristic analysis was conducted to determine the SDS score that equates to a remission of depression symptoms (i.e. HAM-D17≤7). An approximate three-point difference between active treatment and placebo on the SDS (2.8) and WHO-5 (2.5) was determined to be clinically relevant in relation to improvements in depressive symptoms. An SDS of less than or equal to 7 was equivalent to a remission of depression symptoms, providing a definition of functional remission. A better understanding of the relationship between depressive symptoms and functional impairment and well-being may provide clinicians with a more comprehensive means of assessing treatment effects in major depressive disorder.International clinical psychopharmacology 01/2012; 27(1):1-7. DOI:10.1097/YIC.0b013e32834c2488 · 3.10 Impact Factor