Cochrane Database Syst Rev

Cochrane review: Atypical antipsychotics for autism spectrum disorder

June 2, 2025

Study details: This 2025 Cochrane network meta-analysis included 17 randomized controlled trials with 1,027 participants (predominantly children) comparing risperidone, aripiprazole, lurasidone, and olanzapine to placebo or each other in individuals with autism spectrum disorder (ASD). The primary outcome was short-term change in irritability; secondary outcomes included aggression, obsessive-compulsive behaviors, inappropriate speech, weight gain, and extrapyramidal symptoms.

Results: Risperidone and aripiprazole may reduce irritability in children with ASD compared with placebo (mean difference [MD] for risperidone: -7.89, 95% confidence interval [CI], -9.37 to -6.42; aripiprazole: -6.26, 95% CI -7.62 to -4.91; both low-certainty evidence). Lurasidone probably has little to no effect (MD -1.30, 95% CI -5.46 to 2.86; moderate-certainty). Evidence for effects on aggression, weight gain, and extrapyramidal symptoms was very uncertain, with increased risk of weight gain and extrapyramidal symptoms suggested but not definitive. Data on adults were scarce.

Clinical impact: Risperidone and aripiprazole remain the best-supported atypical antipsychotics for short-term management of irritability in children with ASD, but clinicians should be cautious given the low certainty of evidence and potential for adverse effects. There is insufficient evidence to support lurasidone or olanzapine, and data in adults are lacking. Ongoing need exists for larger, high-quality RCTs to clarify long-term efficacy and safety.

Source:

Meza N, et al. (2025, May 12). Cochrane Database Syst Rev. Atypical antipsychotics for autism spectrum disorder: a network meta-analysis. https://pubmed.ncbi.nlm.nih.gov/40396498/