One of a newer class of anti-psychotic medications was successful and well-tolerated for the treatment of serious behavioral disturbance associated with autistic disorder in children aged 5 to 17, researchers in a multi-site, eight-week, placebo-controlled clinical trial have found. The trial was funded by the National Institute of Mental Health (NIMH), and its findings are being published this week in the New England Journal of Medicine.
“Risperidone proved safe and successful in the short-term treatment of children and adolescents with autism characterized by symptoms such as severe tantrums, aggression and self-injury,� said Dr. James McCracken, director of child and adolescent psychiatry at the UCLA Neuropsychiatric Institute and principal investigator at the site. “A six-month follow-up showed that over two-thirds of the treated subjects continued to show benefits from treatment.�
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 and tantrums in response to routine environmental demands. For these disturbances, behavior therapy and medications are the two main forms of treatment.
Researchers randomly assigned 101 subjects, 82 males and 19 females, aged 5 to 17, to receive either placebo or risperidone, one of a new class of anti-psychotics called “atypical.�
Using a stringent definition of improvement, the study found risperidone to be significantly more effective than placebo in improving behavior. Sixty-nine percent of the children randomly assigned to risperidone were much or very much improved at the end of the study, as compared with only 12 percent in the placebo group. This is the largest positive effect by a medication ever observed in children with autism.
Risperidone was in general well-tolerated, with few neurological side effects. However, risperidone was associated with a substantial increase in body weight (an average of about six pounds in the eight-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 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 to adults with schizophrenia, with fewer neurological side effects than older medications.
Few studies of atypical anti-psychotics as treatments for children with autism have been published. The primary goal of this study was to evaluate the efficacy and safety of risperidone, the first widely available atypical, in children with autism accompanied by serious behavioral disturbance.
The study was conducted at five sites of the Research Units of Pediatric Psychopharmacology network, which is funded by NIMH. The 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.
In addition to the UCLA Neuropsychiatric Institute, study sites included Yale University, Ohio State University, Indiana University, and Kennedy Krieger Institute/Johns Hopkins University.
NIMH is one of the 26 components that make up the National Institutes of Health, the federal government’s primary agency for biomedical and behavioral research. The National Institutes of Health is part of the U.S. Department of Health and Human Services.
The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seek to develop effective treatments for neurological and psychiatric disorders, improve access to mental health services and shape national health policy regarding neuropsychiatric disorders.