Analysis of Suicidality in Pooled Data From 2 Double-Blind, Placebo-Controlled Aripiprazole Adjunctive Therapy Trials in Major Depressive Disorder

Objective: To assess the impact of adjunctive aripiprazole versus adjunctive placebo treatment on suicidality in patients with major depressive disorder.

Method: Data were pooled from 2 identical aripiprazole augmentation studies. Patients with DSM-IV-TR-diagnosed major depressive disorder with an inadequate response to 8 weeks of prospective antidepressant treatment were randomly assigned to adjunctive placebo or adjunctive aripiprazole (2-20 mg/d) treatment for 6 weeks. Adverse events related to suicidality were identified in the adverse event database using the Medical Dictionary for Regulatory Activities-preferred term. Treatment-emergent suicidal ideation was defined using item 10 (suicidality) of the Montgomery-Åsberg Depression Rating Scale (MADRS) and item 18 (suicidality) of the Inventory of Depressive Symptomatology (IDS).

Results: In total, 737 patients were included in the safety database (aripiprazole n = 371; placebo n = 366). No suicides were reported. There were no treatment-emergent, suicide-related adverse events in the aripiprazole group; 2 patients in the placebo group had ≥ 1 adverse event related to suicide (both suicidal ideation). More placebo than aripiprazole patients > 25 years old experienced a 2-point (P < .01) or 1-point (P < .05) worsening of MADRS item 10 scores. For this age group, 2-point improvement in MADRS item 10 scores and 1-point improvement of IDS item 18 scores were significantly more common in aripiprazole patients than placebo patients (both P < .05).

Conclusions: This post hoc analysis demonstrated that adjunctive aripiprazole treatment in patients with depression with a history of an inadequate response to antidepressant medication is associated with a decreased rate of suicidality in a group of subjects not at significant risk. Prospective trials directly assessing suicidality are needed to further understand the benefits of an adjunctive antipsychotic in an at-risk population.

Trial Registration: clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758

J Clin Psychiatry

Submitted: June 30, 2009; accepted October 19, 2009.

Online ahead of print: August 24, 2010 (doi:10.4088/JCP.09m05495gre).

Corresponding author: R. H. Weisler, MD, Department of Psychiatry and Behavioral Science, Duke University Medical Center, University of North Carolina at Chapel Hill, 700 Spring Forest, Ste 125, Raleigh, NC 27609 ([email protected]).