Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges

Abstract

BACKGROUND Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g. , aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits. AIM To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD. METHODS Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I 2 to quantify heterogeneity. RESULTS Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I 2 approximately 72%). Risperidone carries a greater metabolic burden (e.g. , weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies. CONCLUSION The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.