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J Affect Disord. 2014 Jun;162:20-5. doi: 10.1016/j.jad.2014.03.017. Epub 2014 Mar 24.

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

Author information

  • 1Yale School of Medicine, New Haven, CT, USA.
  • 2Otsuka America Pharmaceutical, Inc., Princeton, NJ, USA.
  • 3Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ, USA.
  • 4Bristol-Myers Squibb, Plainsboro, NJ, USA.
  • 5Bristol-Myers Squibb, Wallingford, CT, USA.
  • 6Yale School of Medicine, New Haven, CT, USA; Bristol-Myers Squibb, Wallingford, CT, USA.
  • 7Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address:



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.


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.


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.


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.


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: NCT00095823, NCT00105196, and NCT00095758.

Copyright © 2014. Published by Elsevier B.V.


Antidepressant therapy; Augmentation; Major depressive disorder; Symptom severity

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