Systematic Review and Meta-analysis: Efficacy of Pharmacological Interventions for Irritability and Emotional Dysregulation in Autism Spectrum Disorder and Predictors of Response

J Am Acad Child Adolesc Psychiatry. 2023 Feb;62(2):151-168. doi: 10.1016/j.jaac.2022.03.033. Epub 2022 Apr 22.

Abstract

Objective: Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response.

Method: Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2).

Results: A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p > .05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (β = -0.049, p = .026) were associated with a lower efficacy.

Conclusion: Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.

Keywords: autism spectrum disorder; emotional dysregulation; irritability; meta-analysis; psychopharmacology.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents* / pharmacology
  • Antipsychotic Agents* / therapeutic use
  • Aripiprazole
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Autism Spectrum Disorder* / drug therapy
  • Autism Spectrum Disorder* / psychology
  • Humans
  • Risperidone / therapeutic use

Substances

  • Risperidone
  • Aripiprazole
  • Antipsychotic Agents