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.
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- "Despite recent focus on assessing functional impairment as an important ‘real-world’ outcome of antidepressant treatment (Zimmerman et al., 2006; Sheehan and Sheehan, 2008; Soares et al., 2009; Langlieb and Guico-Pabia, 2010; Sheehan et al., 2011; Mancini et al., 2012), there have been relatively few studies examining whether there are baseline characteristics that predict the likelihood of improved functional impairment during treatment. One recent post-hoc analysis of a large pool of data from studies on the SNRI duloxetine versus placebo reported that female sex, a shorter time since the first depressive episode, absence of previous antidepressant use, and mild versus more severe pain were all prognostic factors for improved functioning following antidepressant treatment (Mancini et al., 2012). "
ABSTRACT: Major depressive disorder (MDD) is characterized by increased rates of impaired function and disability. During antidepressant treatment, functional improvement often lags behind symptomatic resolution, and residual impairment is associated with an increased risk for relapse. When evaluating MDD treatments, it is important to assess not only depressive symptoms but also functional outcomes. In this post-hoc analysis, data from five studies were pooled to examine the effect of levomilnacipran extended-release (ER) versus placebo on functional impairment as measured using the Sheehan Disability Scale. The mean change in the Sheehan Disability Scale total score was significantly greater for levomilnacipran ER versus placebo in the overall pooled population, for both sexes, and across all ages. Statistically significantly higher rates of functional response, functional remission, combined (functional and symptomatic) response, and combined remission were achieved with levomilnacipran ER compared with placebo in the pooled population, as well as in the male, female, younger, and middle-aged population subgroups. The levomilnacipran ER group also showed significantly improved functional outcomes versus placebo regardless of baseline depression severity. Similarly, functional impairment was significantly improved and higher functional and combined response and remission rates were achieved with levomilnacipran ER compared with placebo regardless of the baseline level of functional impairment.International clinical psychopharmacology 03/2014; 29(4). DOI:10.1097/YIC.0000000000000033 · 2.46 Impact Factor
Mental Illnesses - Evaluation, Treatments and Implications, 01/2012; , ISBN: 978-953-307-645-4
- "Another review of nine studies also demonstrated its short-term efficacy for MDD (Thase et al., 2009). Another meta-analysis of eight clinical trials suggested that desvenlafaxine could improve the functioning and well-being among MDD patients (Soares et al., 2009). "
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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 · 3.24 Impact Factor