Impact of Risperidone on Repetitive Behavior in Autism: Results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network Trials

Thursday, May 15, 2014
Atrium Ballroom (Marriott Marquis Atlanta)
D. G. Sukhodolsky1, E. I. Anderberg2 and L. Scahill3, (1)Child Study Center, Yale School of Medicine, New Haven, CT, (2)University of Washington, Seattle, WA, (3)Marcus Autism Center, Atlanta, GA
Background: The Children’s Yale Brown Obsessive Compulsive Scales modified for youth with with ASD (CYBOCS-ASD) has demonstrated reliability and validity for measuring repetitive behavior in this population (Scahill et al., 2006). The CYBOCS-ASD was used as an outcome measure in two randomized clinical trials focused on repetitive behavior. The first study evaluated the efficacy of the selective serotonin reuptake inhibitor, citalopram (King et al., 2009). The second trial examined the efficacy of an oral-disintegrating formulation of fluoxetine (Autism Speaks, 2009). In each of these studies, there was no difference between drug and placebo on the CYBOCS-ASD.

Objectives: The purpose of the present report is to examine the sensitivity of the CYBOCS-ASD to detect change in repetitive behavior in a large sample of well-characterized children with ASD treated with risperidone.  

Methods: Data for this set of analyses was compiled from two federally-funded, multisite, randomized clinical trials (Aman et al., 2009; RUPP Autism Network, 2002) and included 225 subjects (187 boys and 38 girls, age 4 to 17 years). In the first trial, subjects were randomly assigned to risperidone (n=49) or placebo (n=52) for eight weeks under double-blind conditions. All 101 participants In Study 1 met DSM-IV criteria for autistic disorder (RUPP Autism Network, 2002). Study 2 included 124 children with autistic disorder, Asperger’s disorder or Pervasive Developmental Disorder.  In Study 2, we used an unbalanced randomization whereby 49 subjects were assigned to risperidone alone and 75 were assigned to risperidone plus parent training. An independent evaluator, who was blinded to treatment assignment and did not engage in discussion of adverse effects, rated the CGI-Improvement scale at each visit and the CYBOCS-ASD at baseline, Weeks 4 and 8. The CYBOCS-ASD includes a symptom checklist and five severity dimensions (Time Spent, Interference, Distress, Resistance and Degree of Control) each rated from 0 to 4 for a total score from 0 to 20.

Results: Using clinician-rated CYBOCS-ASD scores at baseline, Week 4 and Week 8, we compared the change on the CYBOCS across the four treatment groups (placebo and double-blind risperidone in Study 1, risperidone alone and risperidone plus parent training in Study 2) with a linear repeated measures mixed model. After eight weeks of treatment, CYBOCS-ASD total scores declined in the three active treatment groups, and showed no change with placebo. Pair-wise comparisons showed significant differences in the change from baseline to Week 8 between placebo and all active treatment groups: Study 1 blinded risperidone (effect size = 0.74); Study 2 risperidone alone (effect size=0.88) and Study 2 risperidone plus Parent Training (effect size = 0.86). There were no significant differences between any of the active treatment groups.

Conclusions: The CYBOCS-ASD is a reliable measure of repetitive behavior in children with ASD which is sensitive to treatment change and ready for use in clinical trials.