Risperidone in Children With Autism and Serious Behavioral Problems

McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network.

Abstract: N Engl J Med. 2002 Aug 1;347(5):314-21

Findings

Newer types of antipsychotic drugs, which block brain receptors for the neurotransmitters dopamine and serotonin, are effective for treating adults with schizophrenia, and researchers believe that they also may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, there are few studies large studies on the safety and efficacy of these drugs in children with autism.

In this study, the investigators used risperidone, one such antipsychotic drug, and compared it blindly with placebo in children with autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior. The trial was "double-blind," meaning neither child, parent, or doctor knew whether the children were receiving active drug or placebo. A total of 101 children (82 boys and 19 girls, mean age, 8.8 years) were randomly assigned to receive risperidone (49 children) or placebo (52 children). 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 after treatment.

Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9% reduction in the Irritability score, compared with a 14.1% Irritability score decrease in the placebo group, a statistically signifcant difference. The rate of a positive response (defined as at least a 25% decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale) was nearly 70% in the risperidone group (34 of 49 children had a positive response) compared with 12% in the placebo group (6 of 52 had a positive response), a significant difference. Risperidone therapy was also associated with a significant weight gain of 2.7±2.9 kg, as compared with 0.8±2.2 kg with placebo. Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group. 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 found effective for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. Despite this significant result, the authors caution: "Nonetheless, the adverse events observed in our study and the lack of a clear benefit with regard to core symptoms of autism indicate that risperidone should be reserved for treatment of moderate-to-severe behavioral problems associated with autism."