"Although this study did not attempt to treat the core symptoms of autism, our findings suggest that risperidone can be useful in treating moderate to severe behavior problems that are associated with autism in children," said Lawrence Scahill, Ph.D., principal investigator at the Yale Child Study Center site.
Autism is a chronic condition that appears in early childhood and is characterized by core symptoms of impaired social relatedness, delayed language, and restricted patterns of behavior. It affects as many as 20 children per 10,000. Although the causes of autism are unknown for most cases, available evidence implicates abnormalities in brain development. Twin and family studies indicate a strong genetic contribution.
In addition to core symptoms, children with autism frequently exhibit serious behavior disturbances, such as self-injury, aggression, hyperactivity, and tantrums in response to routine environmental demands. For these disturbances, behavior therapy and medications are the two main forms of treatment.
In this multi-site study, researchers randomly assigned 101 children and adolescents, 82 boys and 19 girls, age 5 to 17, to receive either placebo or risperidone, one of a new class of anti-psychotics called atypical.
The study found risperidone to be significantly more effective than placebo in improving behavior. Using a stringent definition of improvement, 69% of the children randomly assigned to risperidone were much or very much improved at the end of the study, as compared with only 12% in the placebo group. This is the largest positive effect by a medication ever observed in children with autism.
Risperidone was well tolerated, with few neurological side effects. However, risperidone was associated with a substantial increase in body weight (an average of about 6 lb increase in the 8 week-period).
Several medications have been used previously to treat autism with limited success. To date, only haloperidol has been shown to be superior to placebo for serious behavior problems in more than one placebo-controlled study. Concerns about neurological and other side effects of haloperidol cause many clinicians to avoid its use in children.
The atypical anti-psychotics are of great interest in treating children with autism because studies have shown them to be beneficial in adults with schizophrenia, with fewer neurological side effects than the older medications.
Few studies of atypical anti-psychotics have been conducted in children with autism. The primary goal of this study was to evaluate the efficacy and safety of risperidone, the first widely available atypical anti-psychotic, in children with autism accompanied by serious behavioral disturbance.
The study was conducted at five sites of the Research Units of Pediatric Psychopharmacology (RUPP) network, which is funded by NIMH. The RUPP network is composed of research units devoted to conducting studies to test the efficacy and safety of medications commonly used by practitioners to treat children and adolescents (off-label use) but not yet adequately tested.
The following are the authors of this report listed by role and study site:
- Yale University, Lawrence Scahill, M.S.N., Ph.D., Principal Investigator; Andres Martin, M.D., Kathleen Koenig, M.S.N., Fred Volkmar, M.D., Deirdre Carroll, M.S.N., Allison Lancor, B.S., Co-Investigators;
- University of California at Los Angeles, James T. McCracken, M.D., Principal Investigator; James McGough, M.D., Bhavik Shah, M.D., Pegeen Cronin, Ph.D., Daniel Hong, M.A., Co-Investigators;
- Ohio State University, Michael G. Aman, Ph.D., Principal Investigator; L. Eugene Arnold, M.ED., M.D., Ronald Lindsay, M.D., Patricia Nash, M.D., Jill Hollway, B.A., Co-Investigators;
- Indiana University, Christopher J. McDougle, M.D., Principal Investigator; David Posey, M.D., Naomi Swiezy, Ph.D., Arlene Kohn, B.A., Co-Investigators;
- Kennedy Krieger Institute at Johns Hopkins University, Elaine Tierney, M.D., Principal Investigator; Jaswinder Ghuman, M.D., Nilda M. Gonzalez, M.D., Marco Grados, M.D., Co-Investigators;
- National Institute of Mental Health, Benedetto Vitiello, M.D., Principal Investigator; Louise Ritz, M.B.A., Co-Investigator;
- Columbia University, Statistician, Mark Davies, M.P.H.;
- Nathan Kline Institute, Data Management, James Robinson, M.E.D., Don McMahon, M.S.
Yale University was the coordinating center for the study. Additional funding was provided by the National Center for Research Resources at the National Institutes of Health (NIH).
More information on the trial and other autism research is available on the NINH Clinical Trials.gov web site at:
http://www.clinicaltrials.gov/show/NCT00005014
and at:
http://www.clinicaltrials.gov/search/term=autism [CONDITION].
NIMH is one of the 26 components that make up NIH, the Federal Government's primary agency for biomedical and behavioral research. NIH is part of the U.S. Department of Health and Human Services.
Journal
New England Journal of Medicine