Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

Pandina, Gahan; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

doi:10.1007/s10803-006-0234-7

Cited by 121 publications

(101 citation statements)

References 26 publications

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“…The ABC-I measures the emotional and behavioral symptoms of ASD, including aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. Since its use in the seminal studies with risperidone, 12,13 the ABC-I has been accepted as the gold standard for measuring IA in medication trials for ASD. Therefore, we used the ABC-I as the primary endpoint for our meta-analysis in this study.…”

Section: Meta-analysismentioning

confidence: 99%

“…12,13,[19][20][21][22][23][25][26][27]29,30,34,35,38,39,41,60 NAC, clonidine, methylphenidate, and tianeptine yielded moderate to large effect sizes. 26,27,30,38,41 In contrast to risperidone and aripiprazole, NAC, methylphenidate, and tianeptine did not cause significant somnolence, EPSs, or weight gain.…”

Section: Figurementioning

confidence: 99%

“…The agency included the target behaviors (ie, aggression, deliberate self-injury, and temper tantrums) under the general heading of "irritability" based on 2 8-week, placebo-controlled trials of risperidone in 156 patients aged 5 to 16 years. 12,13 Subsequently, aripiprazole was also approved for this purpose, with evidence from 2 randomized controlled trials (RCTs) supporting its efficacy and safety in the treatment of IA. Currently, risperidone and aripiprazole are the only medications approved by the FDA for the treatment of IA in people with ASD.…”

mentioning

confidence: 99%

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Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis

et al. 2016

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BACKGROUND: Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families. Although many medications have been tested for IA in ASDs in randomized controlled trials (RCTs), critical quantitative analyses of these trials are lacking in the literature. OBJECTIVES:To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD.DATA SOURCES: Studies were identified from Medline, PsycINFO, Embase, and review articles. METHODS:Original articles on placebo-controlled RCTs of pharmacologic treatments of IA in youth age 2 to 17 years with ASD were included. Data items included study design, study goals, details of study participants, details of intervention, study results, statistical methods, side effects, and risks of bias. The primary study outcome measure was the effect size of reduction in the Aberrant Behavioral Checklist-Irritability (ABC-I) scores in the medication group, as compared with placebo, in RCTs using parallel groups design. RESULTS:Forty-six RCTs were identified. Compared with placebo, 3 compounds resulted in significant improvement in ABC-I at the end of treatment. Risperidone and aripiprazole were found to be the most effective, with the largest effect sizes. Sedation, extrapyramidal sides effects, and weight gain were assessed quantitatively. CONCLUSIONS:Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies.

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Section: Meta-analysismentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

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Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis

et al. 2016

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“…Within the small number of randomized, placebo-controlled trials, several support improvements in overall ASD severity (Luby et al 2006;Nagaraj et al 2006), as well as specific primary ASD symptoms including socialization (Shea et al 2004;Nagaraj et al 2006;Pandina et al 2007), language or communication (Shea et al 2004;Nagaraj et al 2006), and stereotyped, repetitive behaviors (Shea et al, 2004;Nagaraj et al 2006). Open label trials (Zuddas et al 2000;Williams et al 2006;Gencer et al 2008) and naturalistic studies (Masi et al 2003;Capone et al, 2008) also support risperidone's ability to improve social functioning and autistic severity, and one controlled blinded study suggested that this effect was specific to risperidone versus the typical antipsychotic haloperidol .…”

mentioning

confidence: 99%

“…Because the largest trials selected for children with elevated irritability and aggression (McCracken et al 2002), the findings related to risperidone's effects on core symptoms may be less generalizable to more heterogeneous clinical populations with ASD. In studies that have examined effects on social deficits, the instruments used often broadly characterized social function, rather than providing sensitive quantitative measurements of core ASD symptoms (Shea et al, 2004;Pandina et al 2007;Scahill et al 2013). Although the evidence of risperidone's efficacy for irritability in ASD is well established, knowing its impact on primary autistic impairment in children could be critical for treatment planning.…”

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confidence: 99%

Lack of Effect of Risperidone on Core Autistic Symptoms: Data from a Longitudinal Study

Marrus

Underwood-Riordan

Randall

et al. 2014

Journal of Child and Adolescent Psychopharmacology

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Objective: The purpose of this study was to investigate the course of autistic symptoms, using a quantitative measure of core autistic traits, among risperidone-treated children who participated in a 10 year life course longitudinal study. Methods: Parents completed surveys of intervention history, as well as serial symptom severity measurements using the Social Responsiveness Scale (SRS), on their autism spectrum disorder (ASD)-affected children. Fifty participants (out of a total of 184 with full intervention histories) were reported to have been treated with risperidone during the course of the study. Serial SRS scores during risperidone treatment were available for a majority of children whose parents reported a positive effect from risperidone. Results: Two thirds of risperidone-treated children (n = 33) were reported by parents to have improved by taking the medication, with the principal effects described being that children were calmer, better focused, and less aggressive. SRS scores of children reported to have responded positively to risperidone did not improve over time. Conclusions: Risperidone's beneficial effect on aggression and other elements of adaptive functioning were not necessarily accompanied by reduction in core ASD symptoms, as serially assessed by the same caregivers who reported improvement in their children. These results reflect the distinction between reduction in core symptom burden and improvement in adaptive functioning. Given the cumulative risks of atypical neuroleptics, the findings underscore the importance of periodic reevaluation of medication benefit for children with ASD receiving neuroleptic treatment.

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Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

et al. 2013

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IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00086645

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Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

Cited by 121 publications

References 26 publications

Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis

Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis

Lack of Effect of Risperidone on Core Autistic Symptoms: Data from a Longitudinal Study

Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

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