Efficacy of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Response Quartile Analysis and the Predictive Value of Week 2 Early Response

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Objective: To assess varying levels of response to aripiprazole adjunctive to standard antidepressant therapy (ADT) and the predictive value of an early response for a sustained response.

Method: This post hoc analysis of 3 similarly designed randomized, double-blind, placebo-controlled phase 3 studies investigated the efficacy and safety of adjunctive aripiprazole to standard ADT in patients with major depressive disorder (DSM-IV-TR criteria) who had a prior inadequate response to 1–3 ADTs (CN138-139 [September 2004–December 2006], CN138-163 [June 2004–April 2006], and CN138-165 [March 2005–April 2008]). Response levels were defined as percent decreases from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score after 6 weeks of treatment, with a ≤ 25% decrease for minimal, > 25 to < 50% decrease for partial, ≥ 50% to < 75% decrease for moderate, and ≥ 75% decrease for a robust response to treatment.

Results: More patients receiving adjunctive aripiprazole exhibited a partial (23.9% vs 17.9%, P = .017), moderate (23.1% vs 15.0%, P < .001), and robust response (14.3% vs 7.4%, P < .001) compared with adjunctive placebo. Adjunctive aripiprazole treatment compared with adjunctive placebo treatment was associated with a significantly greater proportion of patients achieving an early response (week 2, ≥ 50% reduction in MADRS total score, n = 110/539 vs n = 47/525, P < .001, number needed to treat = 9) and an endpoint response (relative risk = 1.7, 95% CI = 1.4–2.0, P < .001, number needed to treat = 7). A univariate logistic regression analysis revealed that an early response was a significant predictor of endpoint remission (P < .001).

Conclusions: Aripiprazole augmentation was associated with a significantly greater proportion of patients achieving a partial, moderate, or robust response to treatment compared with ADT alone. Patients showing an early response (week 2) to augmentation maintained their response through endpoint, suggesting that clinicians may make clinically meaningful decisions early during treatment.

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

Prim Care Companion CNS Disord 2012;14(3):doi:10.4088/PCC.11m01251

Submitted: July 7, 2011; accepted November 9, 2011.

Published online: May 31, 2012.

Corresponding author: Daniel E. Casey, MD, Department of Psychiatry and Neurology, GH252 Psychiatry Research, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239 (caseyd@ohsu.edu).

Prim Care Companion CNS Disord 2012;14(3):doi:10.4088/PCC.11m01251