Aripiprazole in acute treatment of children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Abstract

Background: Recent randomized controlled trials indicated that aripiprazole was the effective treatment for children and adolescents with autism spectrum disorder (ASD).

Objective: This study systematically reviewed the efficacy, acceptability and tolerability of aripiprazole in treatment of ASD children and adolescents.

Data sources: Electronic search of databases including, Scopus, PubMed, CINAHL and Cochrane Controlled Trials Register was performed in July 2017.

Methods: The full-text versions of included trials were meticulously evaluated and extracted. The main efficacious outcomes consisted of pooled mean change scores of the standardized rating scales for ASD and the pooled response rate.

Results: A total of 408 randomized patients from eligible trials were included for synthesizing in this meta-analysis. The pooled mean change scores in aripiprazole-treated group for the Aberrant Behavior Checklist (ABC)-Irritability, ABC-Hyperactivity/noncompliance, ABC-Inappropriate speech and ABC-Stereotypic behavior were significantly greater than those of the placebo-treated group. Unfortunately, the significant difference between two groups was not found for ABC-Lethargy/social withdrawal. The overall pooled response rate of the aripiprazole-treated group was significantly higher than that of the placebo-treated group. The pooled overall discontinuation rate in aripiprazole-treated group was significantly better than that of placebo-treated group. The pooled discontinuation rates due to adverse events in aripiprazole-treated group significantly differed from the placebo-treated group (RR [95% CI] of 1.43 [0.65, 3.18], I ²=0%).

Limitation: A small number of studies were gathered in this review.

Conclusion: Aripiprazole has efficacy in the treatment of behavioral disturbances, including irritability, hyperactivity/noncompliance, inappropriate speech and stereotypic behavior found in ASD children and adolescents; however, it could not improve the lethargy/social withdrawal in such patients. The present evidence also indicates that it is safe, acceptable and tolerable in such treatment. As a small sample size, further well-defined and large sample size studies should be conducted to warrant those findings.

Keywords: ABC; Aberrant Behavior Checklist; CY-BOCS; Children’s Yale-Brown Obsessive Compulsive Scale; acceptability; efficacy; tolerability.

Figure 1

Summary of risk of bias in a clinical controlled trial of aripiprazole in children and adolescents with ASD. Notes: Green circles indicate low risk of bias; yellow circles indicate unclear risk of bias. Abbreviation: ASD, autism spectrum disorder.

Figure 2

Flow of diagram of study. Abbreviation: EU-CTR, European Union Clinical Trials Register.

Figure 3

The forest plot of ABC-I mean change scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ABC-I, Aberrant Behavior Checklist-Irritability; ASD, autism spectrum disorder; df, degrees of freedom; IV, inverse variance.

Figure 4

The forest plot of ABC-H mean change scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ABC-H, Aberrant Behavior Checklist-Hyperactivity/noncompliance; ASD, autism spectrum disorder; df, degrees of freedom; IV, inverse variance.

Figure 5

The forest plot of ABC-IS mean change scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ABC-IS, Aberrant Behavior Checklist-Inappropriate speech; ASD, autism spectrum disorder; df, degrees of freedom; IV, inverse variance.

Figure 6

The forest plot of ABC-S mean change scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ABC-S, Aberrant Behavior Checklist-Stereotype behavior; ASD, autism spectrum disorder; df, degrees of freedom; IV, inverse variance.

Figure 7

The forest plot of ABC-SW mean change scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ABC-SW, Aberrant Behavior Checklist-Lethargy/social withdrawal; ASD, autism spectrum disorder; df, degrees of freedom; IV, inverse variance.

Figure 8

The forest plot of comparison of relative risk (95% CI) for response rate of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ASD, autism spectrum disorder; df, degrees of freedom; M–H, Mantel–Haenszel test.

Figure 9

The forest plot of CGI-S mean change scores from baseline (95% CI) of aripiprazole vs placebo ASD in children and adolescents. Abbreviations: ASD, autism spectrum disorder; CGI-S, Clinical Global Impression-Severity; df, degrees of freedom; IV, inverse variance.

Figure 10

The forest plot of CY-BOCS mean change scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ASD, autism spectrum disorder; CY-BOCS, Children’s Yale–Brown Obsessive Compulsive Scale; df, degrees of freedom; IV, inverse variance.

Figure 11

The forest plot of CGI-I mean end scores from baseline (95% CI) of aripiprazole vs placebo in ASD in children and adolescents. Abbreviations: ASD, autism spectrum disorder; CGI-I, Clinical Global Impression-Improvement; df, degrees of freedom; IV, inverse variance.

Figure 12

The forest plot of comparison of mean change scores for prolactin level from baseline (95% CI) of aripiprazole vs placebo in autism spectrum disorder in children and adolescents. Abbreviations: df, degrees of freedom; IV, inverse variance.