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

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).