Systematic Review and Meta-analysis: Pharmacological and Non-pharmacological Interventions for Persistent Non-episodic Irritability

This meta-analysis examined the efficacy of available pharmacological and non-pharmacological 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).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.A total of 101 studies were included (80 pharmacological, 13 non-pharmacological, 8 combined). Despite high heterogeneity in effects (IThis meta-analysis provides a comprehensive review of interventions targeting persistent non-episodic 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.