Risperidone treatment of children with autistic disorder: Effectiveness, tolerability, and pharmacokinetic implications

Background: Recent evidence indicates that atypical antipsychotics represent a promising option for the treatment of autistic disorder. In particular, risperidone appears to be effective in treating aggressiveness, hyperactivity, irritability, stereotypies, social withdrawal, and lack of interests. Objective: The aim of the present study was to evaluate the effectiveness and tolerability of risperidone in children with autistic disorder and to examine the correlation between plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and the clinical response. Methods: The effect of treatment with risperidone (0.75–2 mg/day; mean ± SD dose = 1.26 ± 0.42 mg/day) was studied for 24 weeks in 20 children (14 boys, 6 girls) ages 3 to 10 years (mean age 6.0 ± 2.4 years), diagnosed with autistic disorder. Fourteen items selected from the Children’s Psychiatric Rating Scale (CPRS-14) and Clinical Global Impression (CGI) were used for behavioral evaluation. Patients were classified as responders if they showed a 25% or greater decrease on CPRS-14 total score at final evaluation compared with baseline and a final CGI rating of 1 or 2. Patients were rated for extrapyramidal side effects on the Abnormal Involuntary Movement Scale (AIMS). Other side effects, including the expected side effects of atypical antipsychotics drugs, were assessed by a checklist. Blood samples for determination of risperidone and its active metabolite 9-OH-risperidone were obtained after 12 weeks, and serum prolactin levels were measured on admission and at weeks 12 and 24. Results: The psychopathological state, as assessed by CPRS, improved significantly over the duration of treatment. The mean CPRS-14 scores decreased significantly from 63.7 ± 10.0 at baseline to 52.9 ± 14.3 at week 12 (p < 0.01). At the end of 12 weeks of treatment, 8 patients were considered responders, and 10 patients reached a minimal improvement. No further improvement was observed in the following 12 weeks. In all children, serum prolactin levels increased significantly (p < 0.001) from 166 ± 88 UI/mL at baseline to 504 ± 207 UI/mL at week 12 of risperidone treatment. Weight gain and increased appetite were the most common unwanted effects. A mean increase of 3.7 ± 1.7 kg in body weight was observed at final evaluation as compared with baseline. There was no significant correlation between percentimprovement in total CPRS score and the plasma level of risperidone’s active fractions (the sum of the risperidone and 9-OH-risperidone plasma concentration). Conclusions: This study provides further evidence of the beneficial effects of risperidone in children diagnosed with autistic disorder. However, the potential advantages of risperidone should be weighed against the risk of unwanted effects, such as an increase in serum prolactin levels and weight gain. No relation was observed between total plasma risperidone and 9-OH-risperidone concentrations and clinical response.