Aripiprazole for Irritability Associated with Autistic Disorder in Children and Adolescents Aged 6–17 Years

Kelly Blankenship; Craig A Erickson; Kimberly A Stigler; David J Posey; Christopher J McDougle


Pediatr Health. 2010;4(4):375-381. 

In This Article

Clinical Trials

Double-blind Studies

Two large controlled studies of aripiprazole have been performed in children and adolescents with autistic disorder. They were both conducted to determine the short-term efficacy and safety of aripiprazole in treating irritability in children and adolescents with autistic disorder.

The first of the double-blind, randomized, placebo-controlled, parallel-group studies included 218 autistic children and adolescents (aged 6–17 years). The subjects in this study were randomized to receive aripiprazole 5, 10 or 15 mg per day or placebo for 8 weeks. All groups receiving aripiprazole demonstrated significantly greater improvement compared with placebo at week 8 as judged by the Aberrant Behavior Checklist Irritability subscale (ABC-I; primary end point)[11] and the Clinical Global Impressions-Improvement scale (CGI-I).[12] There was no statistically significant difference in efficacy between the aripiprazole 5, 10 and 15 mg groups. Discontinuation rates owing to adverse events were 9.4, 13.6 and 7.4% for the 5-, 10- and 15-mg groups, respectively, and 7.7% for placebo. The three most common adverse events leading to discontinuation were sedation (n = 7), drooling (n = 4) and tremor (n = 4).[13]

The second study was an 8-week, randomized, double-blind, placebo-controlled, parallel-group study with 98 children and adolescents (aged 6–17 years) diagnosed with autistic disorder. Subjects were randomly assigned to receive flexibly-dosed aripiprazole or placebo. At the end of the study, two individuals were receiving 2 mg/day, 13 were receiving 5 mg/day, 16 were receiving 10 mg/day and eight were receiving 15 mg/day of aripiprazole. The mean dose at the end of the study was 8.6 mg/day. Aripiprazole was found to be significantly more efficacious than placebo from week 1 through week 8 as judged by the CGI-I and mean improvement on the ABC-I (primary study end point). Discontinuation rates of 10.6% were noted in the aripiprazole group and 5.9% in the placebo group.[14]

Open-label Trials & Retrospective Chart Reviews

There have been several open-label studies and retrospective chart reviews investigating aripiprazole in individuals with PDDs (Table 1). A naturalistic, open-label study of aripiprazole in five male youths with PDDs aged 5–18 years was performed for a mean duration of 12 weeks (range 8–16 weeks). The dose ranged from 10–15 mg/day. All five subjects were judged to be responders as indicated by a rating of 'much improved' or 'very much improved' on the CGI-I. Aripiprazole was generally well tolerated in this study.[15] A second open-label study with aripiprazole in 25 children and adolescents (aged 5–17 years) diagnosed with Asperger's disorder or PDD not otherwise specified was performed for a duration of 14 weeks. The average dose of medication used in this study was 7.8 mg/day. A total of 22 (88%) of the subjects were deemed to be responders as judged by a score of 'much improved' or 'very much improved' on the CGI-I and a decrease in score of 25% or greater on the ABC-I. Aripiprazole was generally well tolerated in this study.[16]

Two retrospective studies have been performed with aripiprazole in children and adolescents with developmental disabilities. The first included 32 children aged 5–19 years with developmental disabilities that had been prescribed aripiprazole.[17] A total of 24 of the subjects were diagnosed with a PDD and 18 with mental retardation. Target symptoms included aggression, hyperactivity, impulsivity and self-injurious behavior. The mean dose was 10.55 mg/day. The duration of treatment ranged from 6 to 15 months. A total of 18 of the 32 (56%) individuals were judged to be responders by the CGI-I. However, only 9 of the 24 (37%) children with PDDs were noted to improve and only five of the 13 (38%) children with both PDD and mental retardation responded. Side effects caused seven children to stop the study. The second naturalistic retrospective study was performed in 34 subjects (aged 4.5–15 years) diagnosed with a PDD. These children were followed for a mean duration of 7 months. The average CGI severity score prior to starting the study was 5.7. A score of 5 is considered 'markedly ill' and 6 is considered 'severely ill'. The mean CGI severity score at the end of the study was 3.1. A CGI severity score of 3 is considered 'mildly ill' and 4 is considered 'moderately ill'. Aripiprazole was given as monotherapy with a mean final dose of 8.1 mg/day. As many as 11 of the patients (32.4%) were judged to be 'much improved' or 'very much improved' by the CGI-I. A total of 12 of the subjects (35.3%) were determined to be 'minimally improved' and 12 of the children (35.3%) stopped the medication owing to side effects or lack of efficacy.[18]


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