{"doi":"10.1002/14651858.cd011769.pub2","title":"Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD)","abstract":"BACKGROUND: Pharmacological interventions are frequently used for people with autism spectrum disorder (ASD) to manage behaviours of concern, including irritability, aggression, and self-injury. Some pharmacological interventions might help treat some behaviours of concern, but can also have adverse effects (AEs). OBJECTIVES: To assess the effectiveness and AEs of pharmacological interventions for managing the behaviours of irritability, aggression, and self-injury in ASD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 11 other databases and two trials registers up to June 2022. We also searched reference lists of relevant studies, and contacted study authors, experts and pharmaceutical companies. SELECTION CRITERIA: We included randomised controlled trials of participants of any age with a clinical diagnosis of ASD, that compared any pharmacological intervention to an alternative drug, standard care, placebo, or wait-list control. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were behaviours of concern in ASD, (irritability, aggression and self-injury); and AEs. Secondary outcomes were quality of life, and tolerability and acceptability. Two review authors independently assessed each study for risk of bias, and used GRADE to judge the certainty of the evidence for each outcome. MAIN RESULTS: We included 131 studies involving 7014 participants in this review. We identified 26 studies as awaiting classification and 25 as ongoing. Most studies involved children (53 studies involved only children under 13 years), children and adolescents (37 studies), adolescents only (2 studies) children and adults (16 studies), or adults only (23 studies). All included studies compared a pharmacological intervention to a placebo or to another pharmacological intervention. Atypical antipsychotics versus placebo At short-term follow-up (up to 6 months), atypical antipsychotics probably reduce irritability compared to placebo (standardised mean difference (SMD) -0.90, 95% confidence interval (CI) -1.25 to -0.55, 12 studies, 973 participants; moderate-certainty evidence), which may indicate a large effect. However, there was no clear evidence of a difference in aggression between groups (SMD -0.44, 95% CI -0.89 to 0.01; 1 study, 77 participants; very low-certainty evidence). Atypical antipsychotics may also reduce self-injury (SMD -1.43, 95% CI -2.24 to -0.61; 1 study, 30 participants; low-certainty evidence), possibly indicating a large effect. There may be higher rates of neurological AEs (dizziness, fatigue, sedation, somnolence, and tremor) in the intervention group (low-certainty evidence), but there was no clear evidence of an effect on other neurological AEs. Increased appetite may be higher in the intervention group (low-certainty evidence), but we found no clear evidence of an effect on other metabolic AEs. There was no clear evidence of differences between groups in musculoskeletal or psychological AEs. Neurohormones versus placebo At short-term follow-up, neurohormones may have minimal to no clear effect on irritability when compared to placebo (SMD -0.18, 95% CI -0.37 to -0.00; 8 studies; 466 participants; very low-certainty evidence), although the evidence is very uncertain. No data were reported for aggression or self -injury. Neurohormones may reduce the risk of headaches slightly in the intervention group, although the evidence is very uncertain. There was no clear evidence of an effect of neurohormones on any other neurological AEs, nor on any psychological, metabolic, or musculoskeletal AEs (low- and very low-certainty evidence). Attention-deficit hyperactivity disorder (ADHD)-related medications versus placebo At short-term follow-up, ADHD-related medications may reduce irritability slightly (SMD -0.20, 95% CI -0.40 to -0.01; 10 studies, 400 participants; low-certainty evidence), which may indicate a small effect. However, there was no clear evidence that ADHD-related medications have an","journal":"Cochrane Database of Systematic Reviews","year":2023,"id":321278,"datarank":1.1702129218090642,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.5959167123356999,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.5959167123356999,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":43,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00872898","NCT00490802","NCT00773812","NCT00873509","NCT01333072","NCT01227668","NCT00844753","NCT01592747","NCT00380692","NCT00515320","NCT00004486","NCT00211757","NCT01040221","NCT01617447","NCT00576732","NCT00086645","NCT02552147","NCT01911442","NCT00005014","NCT01086475","NCT00183339","NCT00198107","NCT00468130","NCT00498173","NCT01337687","NCT01624675","NCT01908205","NCT01972074","NCT02940574","NCT00365859","NCT01624194","NCT01962870","NCT00178503","NCT00025779","NCT01238575","NCT01944046","NCT01793441","NCT00065962","NCT00453180","NCT01098383","NCT00057408","NCT00198120","NCT01914939","NCT01970345","NCT03553875","NCT04520685","NCT03887676"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1033958,"name":"Nuala Livingstone","orcid":null,"position":1,"is_corresponding":false},{"id":1033303,"name":"Mikaela Jorgensen","orcid":"0000-0002-5490-0819","position":2,"is_corresponding":false},{"id":1033304,"name":"Philip Hazell","orcid":"0000-0002-8085-2996","position":3,"is_corresponding":false},{"id":1033305,"name":"Donna Gillies","orcid":"0000-0002-6216-4559","position":4,"is_corresponding":false},{"id":1033957,"name":"Michelle Iffland","orcid":null,"position":0,"is_corresponding":true}],"reference_count":479,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37811711","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}