Systematic Review and Meta-analysis: Pharmacological and Nonpharmacological Interventions for Persistent Nonepisodic Irritability

Rosanna Breaux, Raman Baweja, Hana May Eadeh, Delshad M. Shroff, Annah R. Cash, Courtney S. Swanson, Amy Knehans, James G. Waxmonsky

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Objective: This meta-analysis examined the efficacy of available pharmacological and nonpharmacological interventions for irritability among youth with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorders (DBD), disruptive mood dysregulation disorder (DMDD), and/or severe mood dysregulation (SMD). Method: Literature searches were conducted in October 2020, resulting in 564 abstracts being reviewed to identify relevant papers, with 387 articles being reviewed in full. A random effects model was used for the meta-analysis, with subgroup meta-regressions run to assess effects of study design, intervention type, medication class, and clinical population. Results: A total of 101 studies were included (80 pharmacological, 13 nonpharmacological, 8 combined). Despite high heterogeneity in effects (I2 = 94.3%), pooled posttreatment effect size for decreasing irritability was large (Hedges’ g = 1.62). Large effects were found for pharmacological (g = 1.85) and nonpharmacological (g = 1.11) interventions; moderate effects were found for combined interventions relative to monotherapy interventions (g = 0.69). Antipsychotic medications provided the largest effect for reducing irritability relative to all other medication classes and nonpharmacological interventions. A large effect was found for youth with ASD (g = 1.89), whereas a medium effect was found for youth with ADHD/DMDD/DBD/SMD (g = 0.64). Conclusion: This meta-analysis provides a comprehensive review of interventions targeting persistent nonepisodic irritability among youth with various psychiatric disorders. Strong evidence was found for medium-to-large effects across study design, intervention type, and clinical populations, with the largest effects for pharmacological interventions, particularly antipsychotic medications and combined pharmacological interventions, and interventions for youth with ASD.

Original languageEnglish (US)
Pages (from-to)318-334
Number of pages17
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number3
StatePublished - Mar 2023

All Science Journal Classification (ASJC) codes

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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