Research study · Journal of Psychopharmacology · 2025
Navigating agitation in neurodevelopmental disorders: A comparative study of pharmacotherapies via network meta-analysis in children and adults with autism spectrum disorder or intellectual disabilities
Verified on PubMed Oxford CEBM Level 1A: Systematic Review & Meta-Analysis
A 2025 systematic review in Journal of Psychopharmacology tested antipsychotic agents in intellectual disability. Several medicines helped more than dummy pills, and people were no more likely to quit taking them. This review suggests that several medicines may calm agitation in people with autism or learning disabilities, and that they were not more likely to.
In plain language
Study overview
This review pooled results from 38 medical studies involving more than 2,500 people, mostly children, who had autism or a learning disability and showed agitation, irritability or aggression. The researchers compared many different medicines with dummy pills to see which helped calm these behaviours.
Findings
Several medicines helped more than dummy pills, and people were no more likely to quit taking them. The strongest evidence was for some antipsychotic medicines and a few newer options.
Explore Dr. Caplan's interactive tool detailing cytochrome P450 pathways, clinical titration intervals, and physician surveillance rules.
The deeper readScientific analysis
Importance: Individuals with autism spectrum disorder (ASD) and intellectual disability often experience persistent challenges related to aggressive behaviour and agitation, highlighting the critical need for evidence-based pharmacological interventions among other strategies. Despite previous network meta-analyses (NMAs), the rapidly evolving landscape of treatment options necessitates ongoing and updated assessments. Objective: To evaluate the efficacy and tolerability of various pharmacotherapies in managing agitation in children and adults with ASD or intellectual disabilities (ID). Methods: Systematic review and NMA of double-blind, randomized controlled trials of pharmacotherapies targeting agitation in neurodevelopmental disorders, following PRISMA guidelines, with risk of bias assessed by the Cochrane Risk of Bias Tool. Primary outcomes were response (50% reduction in agitation severity) and all-cause treatment discontinuation. Results: Data from 38 eligible trials involving 2503 participants were analysed. Arbaclofen, risperidone plus buspirone, omega-3 fatty acids, risperidone plus palmitoylethanolamide, aripiprazole and risperidone demonstrated significant efficacy in reducing agitation compared to placebo. These treatments were generally well-tolerated, with no significant increase in all-cause dropouts compared to placebo. Conclusions: Several pharmacotherapies were effective and well-tolerated in managing agitation in children and adults with ASD or ID. Ongoing research is needed to keep treatment strategies aligned with the evolving clinical landscape.
The paper
Citation
Bahji A, Forth E, Nasar A, Waqas A, Hawken ER, Ayub M Navigating agitation in neurodevelopmental disorders: A comparative study of pharmacotherapies via network meta-analysis in children and adults with autism spectrum disorder or intellectual disabilities. Journal of Psychopharmacology (2025). PubMed 39690490 · DOI
Limitations the authors noted
Most evidence from indirect comparisons, which are more susceptible to bias; small, imprecise and potentially underpowered estimates for some drugs. Few trials per agent; only 7 ID-only trials, too few for a reliable sub-analysis. Limited generalizability beyond agitation symptom clusters; heterogeneity from non-standardized protocols. Co-morbidity poorly reported or excluded; longer-term outcomes rarely measured. Aggression and agitation treated as overlapping constructs; possible publication bias. Only 2 valproic acid studies; few adult-focused trials.
In practice
Why this matters
This review suggests that several medicines may calm agitation in people with autism or learning disabilities, and that they were not more likely to be stopped than dummy pills. It does not establish which medicine is best for any one person, because most comparisons were indirect, the trials were small, and side effects such as weight gain were not fully resolved. Clinicians should treat it as a guide to what has been tested so far, with long-term safety and effects in adults still open questions.
Frequently asked questions
Clinical Questions & Answers
What were the primary clinical findings regarding Antipsychotic agents and Intellectual disability?
Several medicines helped more than dummy pills, and people were no more likely to quit taking them. The strongest evidence was for some antipsychotic medicines and a few newer options.
What study limitations or clinical safeguards should patients keep in mind?
Most evidence from indirect comparisons, which are more susceptible to bias; small, imprecise and potentially underpowered estimates for some drugs. Few trials per agent; only 7 ID-only trials, too few for a reliable sub-analysis. Limited generalizability beyond agitation symptom clusters;...
Browse related research
Condition: Intellectual disability Condition: Psychomotor agitation Topic: Antipsychotic agents
Related on CED Clinic
Back to Daily Research and Patient Questions
Reviewed by Dr. Caplan on November 2, 2026.
This page is general education about a published study. It is not medical advice and does not create a doctor-patient relationship. For care specific to you, book a consultation.