Article

Long-Term Effects of Risperidone in Children With Autism Spectrum Disorders: A Placebo Discontinuation Study

Department of Psychiatry, University of Groningen, Groningen, Groningen, Netherlands
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 6.35). 12/2005; 44(11):1137-44. DOI: 10.1097/01.chi.0000177055.11229.76
Source: PubMed

ABSTRACT The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available.
Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire.
Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects.
This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.

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    • "Functional polymorphisms which affect receptor availability, either post- or presynaptically, may contribute to the impairments found in individuals with autism [6]. The role of the DRD2 gene in autism susceptibility was suggested by the fact that antipsychotic medications, which prevent dopamine D2 receptor activation, improve the core symptoms of ASDs [7]. "
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    • "Risperidone, a benzisoxazole derivative, is a novel antipsychotic agent that combines potent serotonin (5-hydro- xytryptamine, 5-HT2) and dopamine (D2) receptor antagonism [1]. Risperidone is a widely prescribed atypical antipsychotic agent that seems to be effective in behavioral problems, including hyperactivity, irritability, aggressiveness, self-injurious behavior, and stereotypies [2]. Several studies in adolescents demonstrate the effectiveness of risperidone for treating disruptive and aggressive behaviors [3]. "
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    • "The QTDT results support an association of the DRD2 and PPP1R1B loci with autism (Table 4). A role for the DRD2 gene in autism susceptibility is suggested by the fact that antipsychotic medications, which prevent dopamine D2 receptor activation, improve the core symptoms of ASDs [55]. Postsynaptic D2 receptors and presynaptic D2 autoreceptors are involved in the DAergic modulation of cognitive and emotional processes that are impaired in individuals with autism [56,57]. "
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