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.


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.
Weisler
R H
RH
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
Khan
A
A
Trivedi
M H
MH
Yang
H
H
Eudicone
J M
JM
Pikalov
A
A
Tran
Q V
QV
Berman
R M
RM
Carlson
B X
BX
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
D000928:Antidepressive Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole