Beneficial Effects of Adjunctive Aripiprazole in Major Depressive Disorder Are Not Dependent on Antidepressant Therapy History: A Post Hoc Analysis of 3 Randomized, Double-Blind, Placebo-Controlled Trials



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Objective: To determine whether switching within or between antidepressant therapy (ADT) classes prior to the use of adjunctive antipsychotic treatment is associated with different outcomes in major depressive disorder (MDD).

Method: This was a post hoc analysis of pooled data from 3 similar, multicenter, randomized, double-blind, placebo-controlled registrational studies of aripiprazole adjunctive to ADT conducted between September 2004 and April 2008. The trials comprised the following 3 phases: a 7- to 28-day screening phase, an 8-week single-blind prospective treatment phase, and a 6-week double-blind, randomized phase. Patients were aged 18–65 years and met DSM-IV-TR criteria for MDD. Patients with an inadequate response to ADT during the screening phase entered the prospective treatment phase, during which they were switched to another ADT medication of either the same or a different class. Those patients with an inadequate response were then randomized to double-blind adjunctive aripiprazole or adjunctive placebo and followed for 6 weeks.

Results: Mean improvement in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole versus adjunctive placebo for both between-class (−9.2 vs −6.2, P < .001) and within-class (−9.8 vs −6.6, P < .001) switch groups. Relative risks for response were 1.6 (95% CI = 1.3–2.1) for those who switched between classes and 1.7 (95% CI = 1.2–2.2) for those who switched within class.

Conclusions: Augmentation with aripiprazole, after either a between-class or within-class switch following initial ADT failure, is an effective option for patients with nonresponsive MDD. In contrast to current strategies employed in clinical practice, these results suggest that adjunctive aripiprazole is a logical strategy in patients unresponsive to ADT.

Trial Registration: identifiers: NCT00105196, NCT00095758, NCT00095823

Prim Care Companion CNS Disord 2012;14(6):doi:10.4088/PCC.12m01380

Submitted: March 20, 2012; accepted August 15, 2012.

Published online: November 22, 2012.

Corresponding author: David L. Dunner, MD, FACPsych, Center for Anxiety and Depression, 7525 SE 24th St, Ste 400, Mercer Island, WA (

Prim Care Companion CNS Disord 2012;14(6):doi:10.4088/PCC.12m01380