Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine

Abstract

Objective: This post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.

Methods: Data were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0-3), moderate (4-6), and marked/extreme (7-10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.

Results: Greater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (all p ≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (all p<0.0001).

Conclusions: Treatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.

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

Keywords: Antidepressants; Sheehan Disability Scale; functional outcomes; major depressive disorder; treatment outcome.

Figures

Figure 1

Proportions of patients with categorical improvements from moderate/extreme at baseline to mild/no impairment at week 8 (LOCF), from marked/extreme at baseline to moderate/no impairment at week 8 (LOCF), and from marked/extreme at baseline to mild/no impairment at week 8 (LOCF) in each SDS subscale, by treatment group. LOCF=last observation carried forward; SDS=Sheehan Disability Scale. *p<0.001 vs. placebo; †p<0.01 vs. placebo; ‡p<0.05 vs. placebo.

Figure 2

Estimated odds ratios for categorical improvements in SDS subscales, desvenlafaxine versus placebo. (A) Improvement from moderate/extreme impairment (≥4) at baseline to mild/no impairment (≤3) at week 8 (LOCF). (B) Improvement from marked/extreme impairment (≥7) at baseline to moderate/no impairment (≤6) at week 8 (LOCF). (C) Improvement from marked/extreme impairment (≥7) at baseline to mild/no impairment (≤3) at week 8 (LOCF). (D) Improvement of ≥1 category in each scale from baseline to week 8 (LOCF). CI=confidence interval; LOCF=last observation carried forward; SDS=Sheehan Disability Scale.

Figure 3

Percentage change from baseline over time in SDS total and subscale scores. (A) SDS work/studies score. (B) SDS social life/leisure activities score. (C) SDS family life/home responsibilities score. (D) SDS total score. LOCF=last observation carried forward; SDS=Sheehan Disability Scale.

Figure 4

Proportions of patients who shifted to mild/no impairment (SDS subscale score ≤3) at week 8 (LOCF) by no early improvement vs. early improvement at week 2. Patients with marked/extreme impairment (≥7) at baseline only. Early improvement significantly predicted functional response at week 8 (LOCF) on each subscale for all treatment groups (all p<0.0001). LOCF=last observation carried forward; SDS=Sheehan Disability Scale.