Comparative Effectiveness of Propranolol Versus Risperidone in Children with Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition, affecting one in every 68 children in India. It is associated with social communication deficits and restricted, repetitive behaviors, for which pharmacological options are currently limited. Risperidone demonstrates modest efficacy in core domains and has an adverse metabolic profile. Propranolol, a beta-adrenergic antagonist, is an emerging candidate that may modulate autonomic dysregulation implicated in ASD. Methods: Based on DSM-5 criteria, 55 children (4–12 years), diagnosed with ASD, were randomized to receive either propranolol ( n = 30) or risperidone ( n = 30), in a prospective, 12-week, open-label trial, conducted at a tertiary center in India. Indian Scale for Assessment of Autism (ISAA), Clinical Global Impressions Scale (Clinical Global Impressions-improvement Scale), Spence Children’s Anxiety Scale, Social Responsiveness Scale, Second Edition, and Aberrant Behavior Checklist were used to measure outcomes at baseline, 4, 8, and 12 weeks, along with side effects monitoring. Results: Significant improvement was seen on ISAA in both groups, with no between-group differences at 12 weeks ( P = .11). Risperidone exhibited greater improvements in irritability and hyperactivity, whereas propranolol was associated with more pronounced change in the domains of social phobia, social withdrawal and generalized anxiety ( P < .05). The risperidone group was associated with a significant increase in weight at the end of 12 weeks, and the propranolol group was associated with irritability and one episode of syncope. Conclusion: The present study provides preliminary exploratory evidence suggesting that propranolol may be a candidate for further evaluation in children with ASD, particularly those with prominent anxiety and social withdrawal. Risperidone demonstrated greater efficacy for behavioral symptoms such as irritability and hyperactivity. These findings are hypothesis-generating and require replication in adequately powered, double-blind, placebo-controlled trials before any firm clinical conclusions can be drawn.