A Post Hoc Analysis of the Effect of Weight on Efficacy in Depressed Patients Treated With Desvenlafaxine 50 mg/d and 100 mg/d

Abstract

Objective: To assess the effect of baseline body mass index (BMI) on efficacy and weight change in adults with major depressive disorder (MDD) treated with desvenlafaxine or placebo in a pooled, post hoc analysis.

Method: Adults with MDD were randomly assigned to placebo or desvenlafaxine (50 mg or 100 mg) in 8 short-term, double-blind studies and 1 longer-term randomized withdrawal study (the studies were published between 2007 and 2013). Change from baseline in 17-item Hamilton Depression Rating Scale (HDRS-17) total score at week 8 was analyzed in normal (BMI ≤ 25 kg/m(2)), overweight (25 kg/m(2) < BMI ≤ 30 kg/m(2)), and obese (BMI > 30 kg/m(2)) subgroups using analysis of covariance (ANCOVA). Weight change was analyzed in BMI subgroups using ANCOVA and a mixed-effects model for repeated measures.

Results: Desvenlafaxine 50 mg/d or 100 mg/d improved HDRS-17 scores significantly from baseline to week 8 (last observation carried forward) versus placebo in all BMI subgroups (normal: n = 1,122; overweight: n = 960; obese: n = 1,302; all P ≤ .0027); improvement was greatest in normal BMI patients. There was a statistically significant decrease in weight (< 1 kg) with short-term desvenlafaxine 50 mg/d and 100 mg/d versus placebo in all BMI subgroups (all P < .0001). In the randomized withdrawal study (n = 548), no statistically significant difference in weight was observed for desvenlafaxine versus placebo in any BMI subgroup. Baseline BMI predicted weight change in short-term and longer-term desvenlafaxine treatment.

Conclusions: Desvenlafaxine significantly improved symptoms of depression versus placebo regardless of baseline BMI. In all BMI subgroups, desvenlafaxine was associated with statistically significant weight loss (< 1 kg) versus placebo over 8 weeks, but no significant differences longer term.

Trial registration: ClinicalTrials.gov identifiers: NCT00072774, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT00887224.

Figures

Figure 1.

HDRS-17 Total Score Mean (SE) Change From Baseline at Week 8 (last observation carried forward) by Baseline BMIa aNormal: BMI ≤ 25 kg/m2 overweight: 25 kg/m2 < BMI ≤ 30 kg/m2, obese: BMI > 30 kg/m2. *P < .001 vs placebo. P < .01 vs placebo. Abbreviations: BMI = body mass index, HDRS-17 = 17-item Hamilton Depression Rating Scale.

Figure 2.

Adjusted Mean (SE) Change From Baseline in Body Weight (observed), Pooled Population A. Normal BMI Subgroup (BMI ≤ 25 kg/m2) B. Overweight Subgroup (25 kg/m2 < BMI ≤ 30 kg/m2) C. Obese Subgroup (BMI > 30 kg/m2) *P ≤ .001, desvenlafaxine 50 mg/d and 100 mg/d vs placebo. †P < .001, desvenlafaxine 50 mg/d vs placebo; P < .01, desvenlafaxine 100 mg/d vs placebo. ‡P < .01, desvenlafaxine 50 mg/d and 100 mg/d vs placebo. §P < .001, desvenlafaxine 50 mg/d vs placebo; P < .05, desvenlafaxine 100 mg/d vs placebo. ||P < .01, desvenlafaxine 50 mg/d vs placebo; P < .001, desvenlafaxine 100 mg/d vs placebo. Abbreviations: BMI = body mass index, LOCF = last observation carried forward.

Figure 2.

Adjusted Mean (SE) Change From Baseline in Body Weight (observed), Pooled Population A. Normal BMI Subgroup (BMI ≤ 25 kg/m2) B. Overweight Subgroup (25 kg/m2 < BMI ≤ 30 kg/m2) C. Obese Subgroup (BMI > 30 kg/m2) *P ≤ .001, desvenlafaxine 50 mg/d and 100 mg/d vs placebo. †P < .001, desvenlafaxine 50 mg/d vs placebo; P < .01, desvenlafaxine 100 mg/d vs placebo. ‡P < .01, desvenlafaxine 50 mg/d and 100 mg/d vs placebo. §P < .001, desvenlafaxine 50 mg/d vs placebo; P < .05, desvenlafaxine 100 mg/d vs placebo. ||P < .01, desvenlafaxine 50 mg/d vs placebo; P < .001, desvenlafaxine 100 mg/d vs placebo. Abbreviations: BMI = body mass index, LOCF = last observation carried forward.

Figure 2.

Adjusted Mean (SE) Change From Baseline in Body Weight (observed), Pooled Population A. Normal BMI Subgroup (BMI ≤ 25 kg/m2) B. Overweight Subgroup (25 kg/m2 < BMI ≤ 30 kg/m2) C. Obese Subgroup (BMI > 30 kg/m2) *P ≤ .001, desvenlafaxine 50 mg/d and 100 mg/d vs placebo. †P < .001, desvenlafaxine 50 mg/d vs placebo; P < .01, desvenlafaxine 100 mg/d vs placebo. ‡P < .01, desvenlafaxine 50 mg/d and 100 mg/d vs placebo. §P < .001, desvenlafaxine 50 mg/d vs placebo; P < .05, desvenlafaxine 100 mg/d vs placebo. ||P < .01, desvenlafaxine 50 mg/d vs placebo; P < .001, desvenlafaxine 100 mg/d vs placebo. Abbreviations: BMI = body mass index, LOCF = last observation carried forward.

Figure 3.

Mean Change From Baseline in Body Weight, Randomized Withdrawal Study A. Mean Change in Body Weight in Open-Label Period, Observed B. Mean Change in Body Weight in Double-Blind Period, MMRM Analysis *P < .05 for desvenlafaxine 50 mg/d vs placebo. Abbreviation: MMRM = mixed-effects model for repeated measures.

Figure 3.

Mean Change From Baseline in Body Weight, Randomized Withdrawal Study A. Mean Change in Body Weight in Open-Label Period, Observed B. Mean Change in Body Weight in Double-Blind Period, MMRM Analysis *P < .05 for desvenlafaxine 50 mg/d vs placebo. Abbreviation: MMRM = mixed-effects model for repeated measures.

Figure 4.

Mean (SE) Change in Body Weight (observed) by Baseline BMI, Randomized Withdrawal Studya A. Mean (SE) Change in Body Weight From Open-Label Baseline (observed) by Baseline BMI, Open-Label period B. Mean (SE) Change in Body Weight From Double-Blind Baseline (observed) by Baseline BMI, Double-Blind Periodb aNormal: BMI ≤ 25 kg/m2, overweight: 25 kg/m2 < BMI ≤ 30 kg/m2, obese: BMI > 30 kg/m2. bDesvenlafaxine vs placebo, all P > .05. *P ≤ .05 vs baseline. †P < .001 vs baseline. ‡P < .01 vs baseline. §P ≤ .001 vs double-blind baseline. ||P < .01 vs double-blind baseline. Abbreviation: BMI = body mass index.

Figure 4.

Mean (SE) Change in Body Weight (observed) by Baseline BMI, Randomized Withdrawal Studya A. Mean (SE) Change in Body Weight From Open-Label Baseline (observed) by Baseline BMI, Open-Label period B. Mean (SE) Change in Body Weight From Double-Blind Baseline (observed) by Baseline BMI, Double-Blind Periodb aNormal: BMI ≤ 25 kg/m2, overweight: 25 kg/m2 < BMI ≤ 30 kg/m2, obese: BMI > 30 kg/m2. bDesvenlafaxine vs placebo, all P > .05. *P ≤ .05 vs baseline. †P < .001 vs baseline. ‡P < .01 vs baseline. §P ≤ .001 vs double-blind baseline. ||P < .01 vs double-blind baseline. Abbreviation: BMI = body mass index.