Risperidone in the Treatment of Disruptive Behavioral Symptoms in Children With Autistic and Other Pervasive Developmental Disorders

Abstract

ABSTRACT. Objective. To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders (PDD).Methods. In this 8-week, randomized, double-blind, placebo-controlled trial, risperidone/placebo solution (0.01-0.06 mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events, and laboratory tests.Results. Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects (risperidone vs placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups.Conclusions. Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children. Pediatrics 2004;114:e634-e641. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2003-0264-F; autistic disorder, pervasive developmental disorders, risperidone.ABBREVIATIONS. PDD, pervasive developmental disorders; EPS, extrapyramidal symptom; CARS, Childhood Autism Rating Scale; ESRS, Extrapyramidal Symptom Rating Scale; ABC, Aberrant Behavior Checklist; N-CBRF, Nisonger Child Behavior Rating Form; VAS, Visual Analog Scale; CGI-C, Clinical Global Impression-Change; ITT, intention-to-treat; RUPP, Research Units on Pediatric Psychopharmacology. T he pervasive developmental disorders (PDD) are a group of neuropsychiatric disorders that include autistic disorder, Asperger's disorder, childhood disintegrative disorder, Rett's disorder, and PDD not otherwise specified. 1 These disorders are characterized by atypical development in social, communicative, and behavior areas. Onset typically occurs within the first years of life. Prevalence rates as high as 63 per 10 000 children have recently been ...

Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions

“…[5][6][7]29 These positive effects were maintained at least during 1 year, which was the maximum period evaluated in this study. As expected from earlier trials, we found a marked increase in BMI, waist circumference and prolactin levels.…”

“…1 According to a recent survey, 31% of children with autism spectrum disorders take an antipsychotic medication, 2 with risperidone one of the most popular atypical antipsychotics prescribed. Several open trials of risperidone in autism (reviewed in 3,4 ) and three placebo double-blind randomized controlled trials, [5][6][7] reported significant improvements in at least half of the patients evaluated. 4,8 Risperidone was shown to be well tolerated and effective in treating aggressiveness, hyperactivity, irritability, self-injurious behaviours, stereotipies, social withdrawal and lack of interest.…”

Change in Autism Symptoms and Maladaptive Behaviors in Adolescents and Adults with an Autism Spectrum Disorder

“…Maladaptive behaviors are behaviors that interfere with everyday activities, and include self-injurious behavior, withdrawal, uncooperative behavior, aggression, and destruction of property. Although maladaptive behaviors are often exhibited by people with ASD (Aman, Lam, & CollierCrespin, 2003;Hollander, Phillips, & Yeh, 2003;Shea et al, 2004) and are noted as an associated condition in the DSM-IV definition of autism (APA, 2000), there has been relatively little research documenting their prevalence and course. A longitudinal study of 967 children with different types of intellectual disabilities reported that children with autism had higher levels of maladaptive behaviors than children with fragile × syndrome, Williams syndrome, Prader-Willi syndrome, Down syndrome, or children with an intellectual disability with no specified etiology (Tonge & Einfeld, 2003).…”

Improving the Prediction of Response to Therapy in Autism

“…The approval was largely based on the findings from two randomized, controlled trials in 79 and 101 children with autistic disorder and severe behavioral problems. 4,5 In the larger study, children in the risperidone group had a 57% reduction in irritability compared to only a 14% reduction among children in the placebo group (p Ͻ 0.001). 4 A second atypical antipsychotic, aripiprazole, was approved in late 2009 for the same indication (irritability) in children with ASD, based on the results from two 8-week randomized, placebo-controlled trials in 98 and 218 patients.…”