title: Safety and Tolerability of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Post Hoc Analysis (studies CN138-139 and CN138-163).
abstract: OBJECTIVE
  To evaluate the safety and tolerability of aripiprazole adjunctive to standard antidepressant therapy (ADT) for patients with major depressive disorder (DSM-IV-TR criteria).
  
  
  METHODS
  Data from 2 identical studies of aripiprazole augmentation (8 weeks of prospective ADT treatment followed by 6 weeks of randomized double-blind adjunctive treatment) were pooled. The incidence of treatment-emergent adverse events (TEAEs) and weight, electrocardiogram (ECG), and laboratory measurements were assessed during the 6-week phase, including time course, severity, resolution, and predictors. The studies were conducted from June 2004 to April 2006 and September 2004 to December 2006.
  
  
  RESULTS
  The safety analysis included 737 outpatients (aripiprazole, n = 371; placebo, n = 366). The majority of patients completed the trials (aripiprazole, 86%; placebo, 88%). Common TEAEs (≥ 5% and twice the placebo rate) with aripiprazole were akathisia (25%), restlessness (12%), insomnia (8%), fatigue (8%), blurred vision (6%), and constipation (5%). Most TEAEs were of mild to moderate severity (aripiprazole, 89%; placebo, 95%). TEAE rates in the aripiprazole and placebo groups were not affected by ADT, age, or gender. Discontinuation due to TEAEs was low (aripiprazole, 3%; placebo, 1%). Mean weight change was higher with aripiprazole versus placebo (1.73 kg vs 0.38 kg, P < .001). At endpoint, clinical laboratory parameters, vital signs, and ECG indices (including QT(c) interval) were similar between groups. Akathisia with aripiprazole generally occurred in the first 3 weeks (76%), was of mild to moderate severity (92%), and led to discontinuation in 3 patients (0.8%). Within the aripiprazole group, age (18-40 years) was the only positive predictor for akathisia.
  
  
  CONCLUSIONS
  In this short-term post hoc analysis, aripiprazole as augmentation to ADT demonstrated a safety and tolerability profile similar to that in monotherapy studies in other psychiatric populations. Controlled long-term safety and efficacy data of aripiprazole as adjunctive to ADT are warranted.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: NCT00095823 (CN138-139) and NCT00095758 (CN138-163).
authors.affiliation: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA. CraigN@lppi.ucsf.edu
authors.forename: J Craig
authors.initials: JC
authors.lastname: Nelson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.forename: Quynh
authors.initials: Q
authors.lastname: Van Tran
authors.forename: Andrei
authors.initials: A
authors.lastname: Pikalov
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Berit X
authors.initials: BX
authors.lastname: Carlson
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Marcus
authors.forename: Robert M
authors.initials: RM
authors.lastname: Berman