Efficacy and safety of risperidone and aripiprazole in reducing severity of irritability in children with autism spectrum disorder: A randomized controlled trial

Abstract

Background: Both risperidone and aripiprazole are effective in reducing irritability severity in children with autism spectrum disorder (ASD). However, head-to-head comparison trials between these two drugs are scarce in the literature and have shown conflicting results. Methods: This trial compared the efficacy and safety of risperidone and aripiprazole in children and adolescents with ASD, aged 6–18 years. After a two-week placebo trial, placebo responders were excluded. The remaining participants were randomized into two groups. The outcomes were the change in the irritability subscale of the Aberrant Behavior Checklist (ABC-I), Childhood Autism Rating Scale (CARS2), Conners' Parent Rating Scale-Revised (CPRS-R), Children's Sleep Habits Questionnaire (CSHQ), Sensory Profile-2 (SP-2), cognition and the nature and frequency of treatment-emergent adverse events. Results: Seventy-two patients (36 in each group) were recruited. Changes in the ABC-I score (−13.6 ± 4.3 vs. -12.2 ± 3.9, p = 0.15), ABC total score (−27.5 ± 15.9 vs. -26.8 ± 15.7, p = 0.85), CARS score (−2.9 ± 0.7 vs. -2.7 ± 0.8, p = 0.26), CPRS-R Global Index T-score (−10.63 ± 8.54 vs. -9.61 ± 8.92, p = 0.62), number of patients with significant sensory processing abnormalities (18/36 vs. 18/36, p = 1.0), CSHQ score (−4.6 ± 3.8 vs. -3.9 ± 3.1, p = 0.39), and full-scale IQ (1.9 ± 1.6 vs. 1.8 ± 1.5, p = 0.75) were comparable between groups. In multivariate regression analysis, CPRS-R Global Index T-score (p = 0.02) and full-scale intelligence quotient (p = 0.03) were independent predictors of changes in the ABC-I score. The frequency of adverse events was similar in both groups. Serum prolactin levels decreased in the aripiprazole group at 12 weeks but increased in the risperidone group. Conclusions: Risperidone and aripiprazole demonstrate comparable efficacy and safety in managing irritability in children and adolescents with ASD. Trial Registry no: Clinical Trial Registry of India (CTRI/2021/12/038721).