A Placebo-Controlled, Fixed-Dose Study of Aripiprazole in Children and Adolescents With Irritability Associated With Autistic Disorder

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 im provements 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 adol escents with irritability associated with autistic disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(11):1110–1119.

Key Words:  aripiprazole , autistic disorder , pediatric. Clinical trial registration information—Study of Aripiprazole in the Treat ment of Children and Adolescents With Autistic Disorder (AD). URL: http://clinicaltrials.gov. Unique identifier: NCT00337571