A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder

J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-1119. doi: 10.1097/CHI.0b013e3181b76658.

Abstract

Objective: To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.

Method: Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions-Improvement score. Safety and tolerability were also assessed.

Results: At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, -12.4; 10 mg/day, -13.2; 15 mg/day, -14.4; versus placebo, -8.4; all p < .05). All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8. Discontinuation rates due to adverse events were as follows: placebo 7.7%, aripiprazole 5 mg/day 9.4%, 10 mg/day 13.6%, and 15 mg/day 7.4%. The most common adverse event leading to discontinuation was sedation. There were two serious adverse events: presyncope (5 mg/day) and aggression (10 mg/day). At week 8, mean weight change (last observation carried forward) was as follows: placebo +0.3 kg, aripiprazole 5 mg/day +1.3 kg, 10 mg/day +1.3 kg, and 15 mg/day +1.5 kg; all p < .05 versus placebo.

Conclusions: Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder.

Trial registration: ClinicalTrials.gov NCT00337571.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adverse Drug Reaction Reporting Systems
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects
  • Aripiprazole
  • Autistic Disorder / diagnosis
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / psychology
  • Child
  • Child Behavior Disorders / diagnosis
  • Child Behavior Disorders / drug therapy*
  • Child Behavior Disorders / psychology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Irritable Mood / drug effects*
  • Male
  • Personality Assessment
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Psychomotor Agitation / diagnosis
  • Psychomotor Agitation / drug therapy
  • Psychomotor Agitation / psychology
  • Quinolones / administration & dosage*
  • Quinolones / adverse effects
  • Self-Injurious Behavior / diagnosis
  • Self-Injurious Behavior / drug therapy
  • Self-Injurious Behavior / psychology
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Piperazines
  • Quinolones
  • Aripiprazole

Associated data

  • ClinicalTrials.gov/NCT00337571