A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders

Background: Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin(2A)-dopamine D-2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Methods: Thirty-one adults (age [mean + SD], 28.1 +/- 7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n= 14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. Results: For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean +/- SD],2.9 +/- 1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. Conclusion: Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.