title: A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients.
  
  
  METHODS
  This multicenter, double-blind, randomized, placebo-controlled, relapse-prevention trial enrolled patients (6-17 years) who met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) criteria for autistic disorder and who also had serious behavioral problems (ie, tantrums, aggression, self-injurious behavior, or a combination of these behavioral problems) between March 2011 and June 2012. In phase 1, single-blind aripiprazole was flexibly dosed (2-15 mg/d) for 13-26 weeks. Patients with a stable response (≥ 25% decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo. Treatment was continued until relapse or up to 16 weeks. The primary end point was time from randomization to relapse.
  
  
  RESULTS
  Eighty-five patients were randomized in phase 2. The difference in time to relapse between aripiprazole and placebo was not statistically significant (P = .097). Kaplan-Meier relapse rates at week 16 were 35% for aripiprazole and 52% for placebo (hazard ratio [HR] = 0.57; number needed to treat [NNT] = 6). The most common adverse events during phase 1 were weight increase (25.2%), somnolence (14.8%), and vomiting (14.2%); and, during phase 2 (aripiprazole vs placebo), they were upper respiratory tract infection (10.3% vs 2.3%), constipation (5.1% vs 0%), and movement disorder (5.1% vs 0%).
  
  
  CONCLUSIONS
  In this study, there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy. However, the HR and NNT suggest some patients will benefit from maintenance treatment. Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01227668.
authors: Child & Adolescent Psychiatry, Johns Hopkins Hospital, Bloomberg Children's Center, 1800 Orleans St, Ste 12344A, Baltimore, MD 21287 rfindli1@jhmi.edu.
authors: Robert L
authors: RL
authors: Findling
authors: Raymond
authors: R
authors: Mankoski
authors: Karen
authors: K
authors: Timko
authors: Katherine
authors: K
authors: Lears
authors: Theresa
authors: T
authors: McCartney
authors: Robert D
authors: RD
authors: McQuade
authors: James M
authors: JM
authors: Eudicone
authors: Joan
authors: J
authors: Amatniek
authors: Ronald N
authors: RN
authors: Marcus
authors: John J
authors: JJ
authors: Sheehan
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068180:Aripiprazole; D001321:Autistic Disorder / Q000150:complications / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D053208:Kaplan-Meier Estimate; D008134:Long-Term Care; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010919:Placebos; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D010919:Placebos; D015363:Quinolones; D000068180:Aripiprazole