(318) Safety and efficacy of second-generation antipsychotics in Autism Spectrum Disorder: a systematic review and network meta-analysis

Background: Second-generation antipsychotics are increasingly used to manage aggressive behavior in Autism Spectrum Disorder (ASD). Limited information exists regarding the comparative efficacy, safety, and prospective cohort studies of these medications.

Objectives: This study aimed to evaluate the safety and efficacy of these antipsychotics in comparison to both placebo and amongst themselves concerning aggressive behavior associated with ASD

Methods: This systematic review of randomized clinical trials (RCT) and prospective cohorts examines the use of second-generation antipsychotics in children and adults diagnosed with ASD. We conducted a comprehensive search across databases, including MEDLINE via PubMed, Embase via Elsevier, Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, Latin American and Caribbean Health Sciences Literature (LILACS) via Virtual Health Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO. Additionally, we explored references from included studies and clinical guidelines, checked ongoing clinical trials on various platforms, and delved into grey literature sources like ProQuest Dissertations and Theses, Portal Capes, Open Grey, as well as relevant journals and conference proceedings. We assessed the outcomes of signs and symptoms of aggressive behavior associated with ASD, measured by the Aberrant Behavior Checklist (ABC-I) and Clinical Global Impressions (CGI) scales, and total discontinuation. Methodological quality was evaluated using Cochrane's Risk of Bias tool version 2.0. Bayesian meta-analysis models summarized primary outcome results, and evidence certainty was assessed using the GRADE tool.

Results: Twelve studies involving 1,101 participants up to 17 years old met the eligibility criteria. No prospective cohort was identified, nor were studies involving adult patients found. Eleven out of the twelve RCTs were funded by the pharmaceutical industry. Risperidone and aripiprazole (mean difference ranging from in ABC-I: -5.7 to -7.1 on a 0 to 45 scale; CGI scale: -0.77 to -0.85 on a 0 to 7 scale) showed superior efficacy over placebo, with a probability of superiority between 99.3% to 100%, yet did not significantly differ from each other. The relative risk of treatment discontinuation ranged from 0.30 to 0.51 among antipsychotics, but there were no notable differences when comparing these medicines to each other. All included studies exhibited high bias risks or concerns, resulting in very low confidence in the evidence.

Conclusions: The antipsychotics showed superior safety and efficacy compared to placebo in ASD but did not demonstrate significant differences when compared to each other.