Structured exercise outperforms pharmacological interventions for social withdrawal and irritability in ASD children and adolescents

Children and adolescents with Autism Spectrum Disorder (ASD) face significant challenges in social communication and repetitive behaviors, impacting their overall health. While non-pharmacological interventions are often the first line, the efficacy of various treatments, both pharmacological and adjunctive, can vary widely across specific behavioral domains. A critical gap exists in understanding the comparative effectiveness of these diverse interventions, making it difficult for clinicians to select the most appropriate, domain-specific therapies to address core ASD symptoms effectively.

Researchers conducted a frequentist network meta-analysis (NMA) of 67 randomized controlled trials (RCTs), encompassing N=4,203 children and adolescents with ASD. Following 2020 PRISMA guidelines, five databases were searched for studies comparing pharmacological, adjunctive, and non-pharmacological interventions. The primary objective was to estimate the comparative efficacy and ranking probabilities (SUCRA) of these interventions across five key behavioral domains: irritability, hyperactivity, social withdrawal, stereotypic behavior, and inappropriate speech.

The NMA established a domain-specific treatment hierarchy for ASD. For irritability, structured exercise ranked highest (SUCRA = 88.0%; SMD = -1.48, 95% CI -2.24 to -0.73), followed by risperidone plus adjunctive anti-inflammatory agents (SUCRA = 72.9%). Pharmacological interventions were most effective for hyperactivity, with other antipsychotic/ADHD medications ranking highest (SUCRA = 95.1%; SMD = -1.85, 95% CI -2.50 to -1.20), ahead of structured exercise (SUCRA = 76.1%).

Similarly, for stereotypic behavior, other antipsychotic/ADHD medications achieved the best performance (SUCRA = 92.0%; SMD = -1.10, 95% CI -1.67 to -0.52). In contrast, social withdrawal responded best to structured exercise (SUCRA = 98.9%; SMD = -1.28, 95% CI -1.96 to -0.60). For inappropriate speech, structured exercise (SUCRA = 80.1%) and probiotics plus oxytocin (SUCRA = 76.4%) demonstrated the highest rankings, with structured exercise showing a significant effect (SMD = -0.80, 95% CI -1.40 to -0.19).