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


CONCLUSIONS
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.


BACKGROUND
ClinicalTrial.gov: NCT00095823, NCT00105196, and NCT00095758.
Yale School of Medicine, New Haven, CT, USA.
Thomas D
TD
Stewart
Otsuka America Pharmaceutical, Inc., Princeton, NJ, USA.
Ainslie
A
Hatch
Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ, USA.
Kimberly
K
Largay
Bristol-Myers Squibb, Plainsboro, NJ, USA.
John J
JJ
Sheehan
Bristol-Myers Squibb, Wallingford, CT, USA.
Sabrina V
SV
Marler
Yale School of Medicine, New Haven, CT, USA; Bristol-Myers Squibb, Wallingford, CT, USA.
Robert M
RM
Berman
Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: CraigN@lppi.ucsf.edu.
J Craig
JC
Nelson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000209:etiology; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index
D000928:Antidepressive Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole
Antidepressant therapy; Augmentation; Major depressive disorder; Symptom severity