The RUPP-PI at Indiana University School of Medicine will capitalize on the site's expertise and experience in pediatric psychopharmacology. In addition, the site will provide training opportunities for young investigators in the neuropsychopharmacology of serious childhood-onset disorders. The proposed treatment protocol will be a 16-week, randomized study of risperidone alone (n=40) vs. risperidone plus a structured behavior therapy program (n=80) in 120 children and adolescents with autistic disorder (autism) and other pervasive developmental disorders (PDDs) who have significant tantrums, aggression, and/or self- injury. Change in these maladaptive behaviors, as well as improvement in adaptive functioning will be determined. Following an additional 8 weeks of stabilization, subjects who show a positive response to combined risperidone plus behavior therapy (estimated sample size of 60) will be randomized to continued treatment with risperidone or gradual discontinuation. The goal of the discontinuation phase is to determine whether the addition of behavior therapy allows for the discontinuation of risperidone. In a previous RUPP Autism Network study, we showed that risperidone was safe and more efficacious than placebo for treating tantrums, aggression, and/or self-injury in children and adolescents with autism. We also demonstrated that these symptoms returned rapidly in the majority of subjects when the risperidone was withdrawn in a placebo-controlled discontinuation phase. The present study will extend these findings and determine if the combination of risperidone and behavior therapy will enhance adaptive functioning in these children and protect against relapse. Side effects and therapeutic response will be carefully monitored. Subjects will be genotyped to explore the relationship between specific serotonin receptor genotypes and treatment response. The proposed study will be conducted by a multisite network that has already shown the capacity to collaborate on the design and conduct of clinical trials in children and adolescents with autism and other PDDs. Furthermore, this five-site network has established reliability on several measures that are relevant to the conduct of clinical trials in this patient population. The RUPP-PI at Indiana University is also prepared to participate in treatment studies involving children and adolescents with other psychiatric disorders.
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