Effect of symptom severity on efficacy and safety of aripiprazole adjunctive to antidepressant monotherapy in major depressive disorder: A pooled analysis.

Abstract: Background: There is a paucity of evidence for outcome predictors in patients with major depressive disorder (MDD) not responding to initial antidepressant therapy (ADT). This post-hoc analysis evaluated whether MDD severity affects response to adjunctive aripiprazole. Methods: Data from 3 randomized, double-blind, placebo-controlled trials of adjunctive aripiprazole in adults with MDD and inadequate response to 1 to 3 ADT trials were pooled and stratified based on Montgomery–Åsberg Depression Rating Scale (MADRS) total score (mild, ≤24; moderate, 25–30; severe, ≥31). Treatment differences in change in MADRS total score and rates of response (≥50% MADRS improvement) and remission (response with MADRS total score ≤10) were analyzed at endpoint. Adverse events were assessed within each subgroup. Results: Aripiprazole produced greater improvement than placebo in the MADRS total score regardless of MDD severity at baseline (between-treatment difference [95% CI]: mild, −2.5 [−4.0 to −1.1]; moderate, −3.2 [−4.9 to −1.6]; severe, −4.5 [−6.8 to −2.2]). Compared with placebo, adjunctive aripiprazole increased the likelihood of response in all subgroups (risk ratio [95% CI]: mild, 1.50 [1.15, 1.95]; moderate, 1.51 [1.09, 2.11]; severe, 1.95 [1.23, 3.10]). Common treatment-emergent adverse events included akathisia and restlessness. Limitations: The original studies were not designed to assess the efficacy of adjunctive aripiprazole by baseline severity, and this post-hoc analysis was not powered to evaluate differences in severity subgroups. Conclusions: In patients who failed to respond to initial ADT, adjunctive aripiprazole was more effective than placebo in mild, moderate, and severe MDD strata. Clinical trial registration: ClinicalTrial.gov: NCT00095823, NCT00105196, and NCT00095758. [Copyright &y& Elsevier]