Risperidone for the Core Symptom Domains of Autism: Results From the Study by the Autism Network of the Research Units on Pediatric Psychopharmacology

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202-4800, USA.
American Journal of Psychiatry (Impact Factor: 13.56). 07/2005; 162(6):1142-8. DOI: 10.1176/appi.ajp.162.6.1142
Source: PubMed

ABSTRACT Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior.
The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales.
Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months.
Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

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    • "Currently, the FDA has only approved the use of the atypical antipsychotics risperidone and aripiprazole for the treatment of irritability in ASD patients [Canitano & Scandurra, 2011; Politte & McDougle, 2014; Rosenbaum, Hyman, Labbate, & Fava, 2005; see McPheeters et al., 2011, for a review]. Risperidone has also been shown to improve clinical ratings of RRBs in ASD while being ineffective at reducing social impairments [McDougle et al., 2005]. Less is known about whether risperidone may be effective in reducing cognitive inflexibility in ASD. "
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    ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with restricted interests and repetitive behaviors (RRBs). RRBs can severely limit daily living and be particularly stressful to family members. To date, there are limited options for treating this feature in ASD. Risperidone, an atypical antipsychotic, is approved to treat irritability in ASD, but less is known about whether it is effective in treating “higher order” RRBs, for example cognitive inflexibility. Risperidone also has multiple receptor targets in which only a subset may be procognitive and others induce cognitive impairment. 5HT2A receptor blockade represents one promising and more targeted approach, as various preclinical studies have shown that 5HT2A receptor antagonists improve cognition. The present study investigated whether risperidone and/or M100907, a 5HT2A receptor antagonist, improved probabilistic reversal learning performance in the BTBR T + tf/J (BTBR) mouse model of autism. The effects of these treatments were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, similar to one in which ASD individuals exhibit impairments, both risperidone (0.125 mg) and M100907 (0.01 and 0.1 mg) improved reversal learning in BTBR mice. Risperidone (0.125 mg) impaired reversal learning in B6 mice. Improvement in probabilistic reversal learning performance resulted from treatments enhancing the maintenance of the newly correct choice pattern. Because risperidone can lead to unwanted side effects, treatment with a specific 5HT2A receptor antagonist may improve cognitive flexibility in individuals with ASD while also minimizing unwanted side effects. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 10/2014; 7(5). DOI:10.1002/aur.1395 · 4.53 Impact Factor
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    • "treatment of irritability, and compulsive and disruptive behaviors has been demonstrated in large-scale, randomized controlled trials (RCTs), little evidence exists for specific benefit for SIB (McCracken et al. 2002; Shea et al. 2004; McDougle et al. 2005; Marcus et al. 2009; Owen et al. 2009). Atypical antipsychotics have also not demonstrated efficacy in reducing SIB in adults with intellectual disability, with or without ASD (Ruedrich et al 2008). "
    Journal of child and adolescent psychopharmacology 05/2014; 24(4). DOI:10.1089/cap.2013.0137 · 3.07 Impact Factor
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    • "Risperidone>placebo for decreases in repetitive behavior (p <0.001) McDougle et al. (2005) 101 5 to 17 "
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    ABSTRACT: The purpose of this paper is to systematically review empirical evidence for the assessment and treatment of obsessive–compulsive disorder (OCD) among individuals with autism spectrum disorders (ASD). Systematic searches were conducted in electronic databases, reference lists, and journals. Fifty-five studies met inclusion criteria: 21 studies investigating prevalence, symptom presentation, and assessment, as well as 34 intervention studies investigating 14 different interventions. Based on the Chambless criteria for treatment efficacy, four treatments (behavior analysis and behavior modification, risperidone, fluoxetine, and fluvoxamine for adults) met criteria for possible efficacious interventions for OCD among individuals with ASD. Positive intervention outcomes were reported in the majority of studies, but there was not enough research to make firm conclusions regarding efficacy of other treatments.
    03/2013; 1(1):62-79. DOI:10.1007/s40489-013-0006-1
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