Risperidone plasma concentrations and side effects/effectiveness in children and adolescents with autism spectrum disorder

Risperidone is one of the most prescribed antipsychotic drug to children and adolescents, however, it is associated with serious side effects, chief among which weight gain. We assessed the relation of risperidone and 9-hydroxyrisperidone PK parameters in children and adolescents with autism spectrum disorder (ASD) with side effects and improvement in behavioural problems in a longitudinal study. Forty-two children and adolescents were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM​) was used for a population pharmacokinetic analysis. A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P < .001). Higher sum trough concentrations also predicted more sedation (P < .05), higher prolactin levels (P < .001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P < .01). These results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems.

Publication History

Article published online:
12 March 2024