title: Analysis of suicidality in pooled data from 2 double-blind, placebo-controlled aripiprazole adjunctive therapy trials in major depressive disorder.
abstract: OBJECTIVE
  To assess the impact of adjunctive aripiprazole versus adjunctive placebo treatment on suicidality in patients with major depressive disorder.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.
authors.affiliation: 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, USA. RWeisler@aol.com
authors.forename: R H
authors.initials: RH
authors.lastname: Weisler
authors.forename: A
authors.initials: A
authors.lastname: Khan
authors.forename: M H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: J M
authors.initials: JM
authors.lastname: Eudicone
authors.forename: A
authors.initials: A
authors.lastname: Pikalov
authors.forename: Q V
authors.initials: QV
authors.lastname: Tran
authors.forename: R M
authors.initials: RM
authors.lastname: Berman
authors.forename: B X
authors.initials: BX
authors.lastname: Carlson
mesh_terms: D000328:Adult; D000367:Age Factors; D017109:Akathisia, Drug-Induced / Q000209:etiology; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D059020:Suicidal Ideation; D013997:Time Factors; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole