Examining the efficacy of adjunctive aripiprazole in major depressive disorder: a pooled analysis of 2 studies

Abstract

Background: Patients with major depressive disorder (MDD) who fail to achieve complete remission with antidepressant therapy may benefit from augmentation therapy with an atypical antipsychotic.

Method: A pooled analysis was performed on 2 identical 14-week studies (8-week prospective antidepressant therapy treatment phase followed by 6-week randomized double-blind phase) evaluating the efficacy of adjunctive aripiprazole (2-20 mg/day) in DSM-IV-TR-defined MDD patients with an inadequate response to antidepressant therapy. Primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from end of the prospective phase (week 8) to end of randomized phase (week 14, last observation carried forward). Subgroup analyses were performed. The key secondary endpoint was mean change in Sheehan Disability Scale (SDS) mean score.

Results: At endpoint, mean change in MADRS total score was significantly greater with adjunctive aripiprazole (-8.7) than with adjunctive placebo (-5.7; p < .001). Except for a differential treatment-by-sex interaction, change in MADRS total scores were consistently greater with adjunctive aripiprazole than with adjunctive placebo, regardless of race, age, episode duration, prior antidepressant therapy response, number of historical treatment failures, severity of depressive symptoms, and antidepressant. At endpoint, MADRS remission rates were significantly greater with adjunctive aripiprazole than with placebo (25.7% vs. 15.4%; p < .001). Adjunctive aripiprazole also demonstrated significantly greater improvements in mean change from baseline in SDS total score than adjunctive placebo (-1.2 vs. -0.6; p = .001).

Conclusion: Augmentation of antidepressant therapy with the atypical antipsychotic aripiprazole resulted in significant efficacy benefits across a range of subgroups of patients with MDD. Further study of a treatment-by-sex interaction is needed.

Trial registration: www.clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.

Figure 1

Mean Change in MADRS Total Score^a,b During the Randomization Phase in Patients With Major Depressive Disorder Randomly Assigned to Adjunctive Aripiprazole or Adjunctive Placebo (efficacy sample; pooled data; ANCOVA; LOCF) ^aMADRS total score is rated from 0 to 60; a negative change indicates an improvement. ^bBaseline scores: placebo, 26.5; aripiprazole, 25.5. **p < .01, ***p < .001 versus adjunctive placebo. Abbreviations: ANCOVA = analysis of covariance, LOCF = last observation carried forward, MADRS = Montgomery-Asberg Depression Rating Scale.

Figure 2

Mean Change in Sheehan Disability Scale (SDS) Mean Scores and Family, Social, and Work and School Items (LOCF) During Double-Blind Treatment ***p ≤ .001 versus adjunctive placebo. Abbreviation: LOCF = last observation carried forward.

Figure 3

Remission^a Rates in the Adjunctive Placebo and Adjunctive Aripiprazole Groups During Double-Blind Treatment ^aRemission equals absolute Montgomery-Asberg Depression Rating Scale (MADRS) total score ≤ 10 and at least 50% reduction in MADRS total score relative to the end of the prospective treatment phase. ***p < .001 versus adjunctive placebo.