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: 7.26). 12/2005; 44(11):1137-44. DOI: 10.1097/01.chi.0000177055.11229.76
Source: PubMed


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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    ABSTRACT: Autism is a neurodevelopmental disorder with indisputable evidence for a genetic component. This work studied the association of autism with genetic variations in neurotransmitter-related genes, including MAOA uVNTR, MAOB rs1799836, and DRD2 TaqI A in 53 autistic patients and 30 healthy individuals. The study also analyzed sequence variations of miR-431 and miR-21. MAOA uVNTR was genotyped by PCR, MAOB and DRD2 polymorphisms were analyzed by PCR-based RFLP, and miR-431 and miR-21 were sequenced. Low expressing allele of MAOA uVNTR was frequently higher in female patients compared to that in controls (OR = 2.25). MAOB G allele frequency was more significantly increased in autistic patients than in controls (P < 0.001 for both males and females). DRD2 A1+ genotype increased autism risk (OR = 5.1). Severity of autism tends to be slightly affected by MAOA/B genotype. Plasma MAOB activity was significantly reduced in G than in A allele carrying males. There was no significant difference in patients and maternal plasma MAOA/B activity compared to controls. Neither mutations nor SNPs in miR-431 and miR-21 were found among studied patients. This study threw light on some neurotransmitter-related genes suggesting their potential role in Autism pathogenesis that warrants further studies and much consideration.
    The Scientific World Journal 12/2013; 2013(3):670621. DOI:10.1155/2013/670621 · 1.73 Impact Factor
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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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    ABSTRACT: An 80-year-old female presented with symptoms of depression, worthlessness, hopelessness, loss of energy, insomnia, impatience, and forgetfulness associated with persecutory delusion that had begun about one year before her visit. She was diagnosed with major depression with psychotic signs and began treatment with risperidone (2 mg/night) and citalopram (20 mg/day). After 20 days, she returned and reported partial improvement in her symptoms, although she had developed severe swelling of the hands and feet. The results of liver and renal function tests and rheumatologic tests were found to be within normal limits. Risperidone was discontinued for a week, and the swelling resolved completely. Risperidone was then administered again, and the swelling returned so that the patient had to discontinue taking the drug. The reappearance of edema on rechallenge is strong evidence implicating risperidone as the cause of the swelling.
    Case Reports in Medicine 11/2012; 2012:540732. DOI:10.1155/2012/540732
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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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    ABSTRACT: The neurotransmitter dopamine (DA) modulates executive functions, learning, and emotional processing, all of which are impaired in individuals with autism spectrum disorders (ASDs). Our previous findings suggest a role for dopamine-related genes in families with only affected males. We examined two additional genes which affect DA function, the DRD2 and PPP1R1B (DARPP-32) genes, in a cohort of 112 male-only affected sib-pair families. Selected polymorphisms spanning these genes were genotyped and both family-based and population-based tests were carried out for association analysis. General discriminant analysis was used to examine the gene-gene interactions in predicting autism susceptibility. There was a significantly increased frequency of the DRD2 rs1800498TT genotype (P = 0.007) in affected males compared to the comparison group, apparently due to over-transmission of the T allele (P = 0.0003). The frequency of the PPP1R1B rs1495099CC genotype in affected males was also higher than that in the comparison group (P = 0.002) due to preferential transmission of the C allele from parents to affected children (P = 0.0009). Alleles rs1800498T and rs1495099C were associated with more severe problems in social interaction (P = 0.0002 and P = 0.0016, respectively) and communication (P = 0.0004 and P = 0.0046), and increased stereotypic behaviours (P = 0.0021 and P = 0.00072). General discriminant analysis found that the DRD2 and PPP1R1B genes additively predicted ASDs (P = 0.00011; Canonical R = 0.26) and explain ~7% of the variance in our families. All findings remained significant following corrections for multiple testing. Our findings support a role for the DRD2 and PPP1R1B genes in conferring risk for autism in families with only affected males and show an additive effect of these genes towards prediction of affected status in our families.
    Behavioral and Brain Functions 05/2012; 8(1):19. DOI:10.1186/1744-9081-8-19 · 1.97 Impact Factor
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