Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study.
OBJECTIVE
To evaluate the efficacy and tolerability of a once-monthly intramuscular (IM) depot formulation of the dopamine partial agonist aripiprazole as maintenance treatment in adults meeting DSM-IV-TR schizophrenia criteria.


METHODS
The study was conducted from July 2008 until February 2011. Subjects requiring chronic treatment with an antipsychotic entered a 4- to 12-week oral stabilization phase and received oral aripiprazole (10-30 mg/d). Subjects meeting stability criteria for 4 weeks entered an IM-depot stabilization phase in which they received 400-mg aripiprazole-IM-depot injections every 4 weeks (single decrease to 300 mg permitted) with coadministration of oral aripiprazole tablets in the first 2 weeks. Subjects meeting stability criteria for 12 consecutive weeks were randomly assigned (2:1) to aripiprazole-IM-depot or placebo during a 52-week, double-blind maintenance phase. The primary outcome measure was time to exacerbation of psychotic symptoms/impending relapse (event). Safety and tolerability were also assessed.


RESULTS
710 patients entered oral stabilization, 576 progressed to IM-depot stabilization, and 403 were randomly assigned to double-blind treatment. The study was terminated early because efficacy was demonstrated by the preplanned interim analysis (conducted after 64 events). Time to impending relapse was significantly delayed with aripiprazole-IM-depot treatment compared with placebo in both the interim analysis and the final analysis (P < .0001, log-rank test). The hazard ratio (placebo/aripiprazole-IM-depot) at final analysis was 5.03 (95% CI, 3.15-8.02). The rate of impending relapse was significantly lower with aripiprazole-IM-depot than placebo at endpoint (final analysis, 10.0% [n = 27/269] vs 39.6% [n = 53/134]). Improvements in Clinical Global Impressions-Severity of Illness scale and Positive and Negative Syndrome Scale total scores were maintained with aripiprazole-IM-depot treatment but showed significant worsening with placebo (change from double-blind baseline, P < .0001 for aripiprazole-IM-depot vs placebo). The most common treatment-emergent adverse events (occurring in ≥ 5% of aripiprazole-IM-depot subjects and greater than placebo) were insomnia, tremor, and headache.


CONCLUSIONS
Aripiprazole-IM-depot significantly delayed time to impending relapse compared with placebo and appears to be a well-tolerated maintenance treatment option for schizophrenia.


BACKGROUND
ClinicalTrials.gov identifier: NCT00705783.
The Zucker Hillside Hospital and The Hofstra North Shore-LIJ School of Medicine, Glen Oaks, NY 11004-1100, USA. psychiatry@nshs.edu
John M
JM
Kane
Raymond
R
Sanchez
Pamela P
PP
Perry
Na
N
Jin
Brian R
BR
Johnson
Robert A
RA
Forbes
Robert D
RD
McQuade
William H
WH
Carson
W Wolfgang
WW
Fleischhacker
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000068180:Aripiprazole; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy*; D055502:Secondary Prevention
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole