ABSTRACT
BACKGROUND: Severe behavior problems in children with autism interfere with treatment. These authors studied the efficacy and safety of risperidone to reduce behavioral problems in a small population of children with autism.
POPULATION STUDIED: The researchers studied 101 children with autistic disorder, as determined by semistructured interview. The children also had severe tantrums, aggression, or self-injurious behavior, or a combination of these behavioral problems. The children (82 boys and 19 girls), aged 5 to 17 years (mean age ± SD, 8.8 ± 2.7 years), weighed at least 15 kg, had a mental age of at least 18 months, and were free of serious medical disorders and other psychiatric disorders requiring medications. Children receiving psychotropic drugs for the treatment of aggressive behavior were not included. Children taking anticonvulsant agents for seizure control were included as long as the dose had not been changed for at least 4 weeks and the child had been seizure-free for the past 6 months.
STUDY DESIGN AND VALIDITY: The study was an 8-week, double-blind, randomized, placebo-controlled trial of risperidone. For children weighing 20 to 45 kg, the researchers started with an initial dose of 0.5 mg at bedtime, increasing the dose to 0.5 mg twice daily after 4 days, to a maximum of 1.0 mg in the morning and 1.5 mg in the evening by day 29. Children weighing less than 20 kg started with an initial dose of 0.25 mg per day, while those children who weighed more than 45 kg received a maximum dose of 1.5 mg in the morning and 2.0 mg in the evening. Each week 2 blinded clinicians evaluated the subjects: one who reviewed side effects and adjusted dose and a second who rated response to treatment.
OUTCOMES MEASURED: Primary outcome measures consisted of the irritability subscale of the Aberrant Behavior Checklist (ABC) (parent/caregiver rating) and the Clinical Global Impressions-Improvement (CGI-I) scale (clinician rating). A positive response was considered to be a 25% reduction in the irritability score combined with a rating of much improved or very much improved on the CGI-I scale. Adverse effects were also assessed through weekly monitoring of weight, vital signs, neurologic and other side effects. Other outcomes included the other subscales of the ABC.
RESULTS: Significantly more children treated with risperidone had a reduction in irritability score by at least 25% and a rating of much improved or very much improved on the CGI-I scale at the end of the 8-week trial (69% vs 12%, number needed to treat = 1.8). Side effects, which were expected and mild, included weight gain and appetite changes, dizziness, drooling, drowsiness, and fatigue. No extrapyramidal symptoms were observed during the study in either group, although tremor was more common in the intervention group (P = .06). Scores on other ABC subscales for stereotypy and hyperactivity also improved significantly.
Risperidone is an effective and relatively safe choice to decrease serious behavior problems—tantrums, aggression, self-injury—in children with autism. Because risperidone was also shown to have only mild adverse reactions that generally would not limit its use in clinical practice, it may offer an advantage over older agents.