Improvement in functional outcomes with adjunctive aripiprazole versus placebo in major depressive disorder: a pooled post hoc analysis of 3 short-term studies

Abstract

Objective: To evaluate the effect of adjunctive aripiprazole to antidepressant therapy (ADT) on functional outcomes, as assessed by the Sheehan Disability Scale (SDS).

Method: A post hoc analysis of pooled data from 3 similarly designed randomized, placebo-controlled trials was conducted (CN138-139 [September 2004-December 2006], CN138-163 [June 2004-April 2006], and CN138-165 [March 2005-April 2008]). Patients with DSM-IV major depressive disorder who had a prior inadequate response to ADT received adjunctive aripiprazole or placebo to standard ADT. The change from baseline to endpoint on total SDS score and on individual SDS domains and the distributional categorical shifts of patient-reported severity of functional impairment on the SDS were assessed.

Results: Aripiprazole compared to placebo augmentation produced significant improvements in self-reported functioning levels in the SDS mean total score (-1.2 vs -0.7, P ≤ .001) and social life (-1.4 vs -0.7, P ≤ .001) and family life (-1.4 vs -0.7, P ≤ .001) domains. Additionally, a significant number of patients exhibited a shift from a severe/moderate level of impairment at baseline to a mild level of functional impairment after 6 weeks of adjunctive aripiprazole treatment compared with placebo in the SDS mean total score (P = .001) and social life (P ≤ .001) and family life (P = .001) scores.

Conclusions: Aripiprazole augmentation of standard antidepressant therapy resulted in significant improvements in both total and individual domains of functioning, as assessed by the SDS, with significant categorical shifts from severe/moderate to mild levels of functioning compared with placebo augmentation.

Trial registration: ClinicalTrials.gov identifiers: NCT00095823, NCT00095758, and NCT00105196.

Figures

Figure 1.

Mean Change From Baseline to Endpoint (last observation carried forward) in Sheehan Disability Scale (SDS) Total Score and Social Life, Family Life, and Work/School Domain Scoresa aNumber of patients completing SDS questionnaire items who received adjunctive aripiprazole: mean score (n = 507), social life (n=508), family life (n = 508), and work/school (n = 384). Number of patients completing SDS questionnaire items who received adjunctive placebo: mean score (n = 492), social life (n = 494), family life (n = 494), and work/school (n = 392). *P ≤ .001.

Figure 2.

Percent Shifts From Moderate/Severe at Baseline (week 8) to Mild at Endpoint (week 14) in Sheehan Disability Scale (SDS) Mean Total Score and Between Baseline and Endpoint Score for Patients Receiving Adjunctive Aripiprazole and Adjunctive Placeboa aNumber of patients completing SDS questionnaire items who received adjunctive aripiprazole: mean score (n = 507), social life (n = 508), family life (n = 508), and work/school (n = 384). Number of patients completing SDS questionnaire items who received adjunctive placebo: mean score (n = 492), social life (n = 494), family life (n = 494), and work/school (n = 392). *P ≤ .001. **P = .001. ***P = .148.

Figure 3.

Relative Risk for Patients to Report a Shift in Functional Severity Between Baseline and Endpoint (last observation carried forward) on the Basis of Treatment: Adjunctive Aripiprazole Versus Adjunctive Placebo Abbreviation: SDS = Sheehan Disability Scale.