Evaluating the Real-World Safety of Atypical Antipsychotics in Paediatric Autism Spectrum Disorder: Lessons from Saudi Arabia’s Pharmacovigilance System

Abstract Background Atypical antipsychotics (AAPs) are increasingly prescribed for paediatric patients with autism spectrum disorder (ASD). However, pharmacovigilance data from Saudi Arabia remain scarce. The aim of this study is to detect and characterise signals associated with AAPs and assess gender- and age-related ADR reporting patterns. Methods A retrospective cross–sectional study with disproportionality analysis was conducted on paediatric patients (0–19 years) using the Saudi Food and Drug Authority (SFDA) database (2021–2024). Disproportionality analyses were performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). Age and gender were assessed using odds ratios (ORs), with Firth penalized logistic regression to confirm associations. Results Overall, 701 ADR reports were analysed. Most involved males (59.91%) and children aged 0-9 years (82.88%). Olanzapine had the highest proportion of serious reports (44.44%). At the system organ class (SOC) level, signals included nervous system disorders with risperidone (ROR 32.61 [16.62–64.00]; PRR 3.49 [2.22–5.47]; IC025 0.08); cardiac and general disorders with quetiapine; haematological, metabolic, and psychiatric disorders with olanzapine; and gastrointestinal disorders with aripiprazole. Gender–adjusted analyses indicated significant variation in selected ADR signals across age groups, while no significant differences were observed by gender. Conclusions This study highlights disproportionality signals associated with AAP use in paediatric patients. Age–related ADR variation supports consideration of age-specific ADR monitoring within current paediatric recommendations. While these findings do not establish causality, they generate hypotheses for further evaluation. Regional pharmacovigilance may complement international paediatric safety monitoring frameworks.