Risperidone Treatment of Autistic Disorder: Longer-Term Benefits and Blinded Discontinuation After 6 Months

• Published in: The American journal of psychiatry Vol. 162; no. 7; pp. 1361 - 1369
• Main Authors: Aman, Michael G, Arnold, L Eugene, Lindsay, Ronald, Nash, Patricia
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01.07.2005; American Psychiatric Association
• Subjects: Adolescent; Aggression - drug effects; Aggression - psychology; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Autism; Autistic Disorder - diagnosis; Autistic Disorder - drug therapy; Autistic Disorder - psychology; Biological and medical sciences; Child; Child Behavior Disorders - diagnosis; Child Behavior Disorders - drug therapy; Child Behavior Disorders - psychology; Child clinical studies; Child, Preschool; Developmental disorders; Drug Administration Schedule; Drug therapy; Female; Humans; Infantile autism; Longitudinal Studies; Male; Medical sciences; Neuropharmacology; Personality Inventory; Pharmacology. Drug treatments; Placebo effect; Placebos; Psychiatric Status Rating Scales; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Risperidone - adverse effects; Risperidone - therapeutic use; Self destructive behavior; Self-Injurious Behavior - diagnosis; Self-Injurious Behavior - drug therapy; Self-Injurious Behavior - psychology; Substance Withdrawal Syndrome - diagnosis; Substance Withdrawal Syndrome - psychology; Treatment Outcome; Human; Atypical antipsychotic; Psychotropic; Neuroleptic; Toxicity; Dopamine antagonist; Serotonin antagonist; Treatment efficiency; Developmental disorder; Serotonine receptor; Autism; Chemotherapy; D2 Dopamine receptor; Treatment; Treatment withdrawal; Risperidone; Child
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.162.7.1361

OBJECTIVE: Risperidone is effective for short-term treatment of aggression, temper outbursts, and self-injurious behavior in children with autism. Because these behaviors may be chronic, there is a need to establish the efficacy and safety of longer-term treatment with this agent. METHOD: The authors conducted a multisite, two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums, aggression, and or self-injurious behavior who showed a positive response in an earlier 8-week trial. Part I consisted of 4-month open-label treatment with risperidone, starting at the established optimal dose; part II was an 8-week randomized, double-blind, placebo-substitution study of risperidone withdrawal. Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale. RESULTS: Part I included 63 children. The mean risperidone dose was 1.96 mg day at entry and remained stable over 16 weeks of open treatment. The change on the Aberrant Behavior Checklist irritability subscale was small and clinically insignificant. Reasons for discontinuation of part I included loss of efficacy (N=5) and adverse effects (N=1). The subjects gained an average of 5.1 kg. Part II included 32 patients. The relapse rates were 62.5% for gradual placebo substitution and 12.5% for continued risperidone; this difference was statistically significant. CONCLUSIONS: Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums, aggression, and or self-injurious behavior. Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects.