Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Gian Loreto D’Alò, Franco De Crescenzo, Laura Amato, Fabio Cruciani, Marina Davoli, Francesca Fulceri, Silvia Minozzi, Zuzana Mitrova, Gian Paolo Morgano, Franco Nardocci, Rosella Saulle, Holger Jens Schünemann, Maria Luisa Scattoni, Massimo Molteni, on behalf of the ISACA guideline working group

Research output: Contribution to journalArticlepeer-review


Background: The net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD. Methods: We performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach. Results: We included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on “restricted and repetitive interests and behaviors” (SMD − 0.21, 95% CI − 0.35 to − 0.07, moderate certainty), “hyperactivity, inattention, oppositional, disruptive behavior” (SMD − 0.67, 95% CI − 0.92 to − 0.42, moderate certainty), “social communication, social interaction” (SMD − 0.38, 95% CI − 0.59 to − 0.16, moderate certainty), “emotional dysregulation/irritability” (SMD − 0.71, 95% CI − 0.98 to − 0.43, low certainty), “global functioning, global improvement” (SMD − 0.64, 95% CI − 0.96 to − 0.33, low certainty), “obsessions, compulsions” (SMD − 0.30, 95% CI − 0.55 to − 0.06, moderate certainty). Antipsychotics were not effective on “self-harm” (SMD − 0.14, 95% CI − 0.58 to 0.30, very low certainty), “anxiety” (SMD − 0.38, 95% CI − 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty). Conclusions: Our systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.

Original languageEnglish
Article number33
Number of pages19
JournalHealth and Quality of Life Outcomes
Issue number1
Publication statusPublished - Dec 2021


  • Adolescents
  • Antipsychotics
  • Autism spectrum disorder
  • Children
  • D2 blockers
  • Guidelines
  • Meta-analysis
  • Systematic review

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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