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Previous Volume 347:314-321 August 1, 2002 Number 5 Next

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ABSTRACT

Background Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited.

Methods We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions — Improvement (CGI-I) scale at eight weeks.

Results A total of 101 children (82 boys and 19 girls; mean [±SD] age, 8.8±2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7±2.9 kg, as compared with 0.8±2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months.

Conclusions Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.

Source Information

Dr. Scahill accepts responsibility for the overall content and integrity of the manuscript.

The authors of this report are James T. McCracken, M.D., James McGough, M.D., Bhavik Shah, M.D., Pegeen Cronin, Ph.D., and Daniel Hong, M.A., University of California, Los Angeles; Michael G. Aman, Ph.D., L. Eugene Arnold, M.D., Ronald Lindsay, M.D., Patricia Nash, M.D., and Jill Hollway, B.A., Ohio State University, Columbus; Christopher J. McDougle, M.D., David Posey, M.D., Naomi Swiezy, Ph.D., and Arlene Kohn, B.A., Indiana University, Indianapolis; Lawrence Scahill, M.S.N., Ph.D., Andres Martin, M.D., Kathleen Koenig, M.S.N., Fred Volkmar, M.D., Deirdre Carroll, M.S.N., and Allison Lancor, B.S., Yale University, New Haven, Conn.; Elaine Tierney, M.D., Jaswinder Ghuman, M.D., Nilda M. Gonzalez, M.D., and Marco Grados, M.D., Kennedy Krieger Institute, Baltimore; Benedetto Vitiello, M.D., and Louise Ritz, M.B.A., National Institute of Mental Health, Bethesda, Md.; Mark Davies, M.P.H., Columbia University, New York; and James Robinson, M.E.D., and Don McMahon, M.S., Nathan Kline Institute, Orangeburg, N.Y.

Address reprint requests to Dr. Lawrence Scahill at the Yale Child Study Center, P.O. Box 207900, New Haven, CT 06520, or at lawrence.scahill{at}yale.edu.

Full Text of this Article

Related Letters:

Risperidone in Children with Autism and Serious Behavioral Problems
Sandler L., Valiquette G., Munarriz R., Bennett L., Goldstein I., Scahill L., Vitiello B., the Research Units on Pediatric Psychopharmacology Autism Network
Extract | Full Text | PDF  
N Engl J Med 2002; 347:1890-1891, Dec 5, 2002. Correspondence

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