title: No Apparent Cardiac Conduction Effects of Acute Treatment with Risperidone in Children with Autism Spectrum Disorder.
abstract: Risperidone is approved for the treatment of serious behavioral problems in children with autism spectrum disorder (ASD). This study examined the effects of risperidone on cardiac conduction in children with ASD.
  
  
  
  Data were collected from an 8-week, five-site trial conducted by the Research Units on Pediatric Psychopharmacology Autism Network. Children (age 5-17 years) were randomly assigned to risperidone (n = 49) or placebo (n = 52) under double-blind conditions. Risperidone was superior to placebo in reducing serious behavioral problems. A standard 12-lead, electrocardiogram (ECG) was obtained in most subjects at screening and week 8. A pediatric electrophysiologist blind to treatment assignment reviewed all available ECGs for readability, abnormalities, and cardiac conduction parameters, including QTc. The electrophysiologist measurements were compared to machine readings. A second blinded electrophysiologist examined all available ECGs for abnormalities and a 20% random sample for QTc.
  
  
  
  Of the 101 randomized subjects in the trial, complete pretreatment and week 8 data were available on 65 subjects (placebo n = 30; risperidone n = 35). The electrophysiologist did not identify any cardiac conduction adverse effects of risperidone and there was no difference in mean change on the QTc compared to placebo. The Bland-Altman plot showed a systematic bias in QTc measurements by the electrophysiologist and machine. Machine readings produced higher values than the electrophysiologist for shorter QTc intervals and machine scoring was lower than electrophysiologist readings for longer QTc values (p = 0.001). Two electrophysiologists had overall percent agreements of 82.9% (95% CI: 76.3 to 89.6) on qualitative assessment and 88.6% (95% CI: 79.3 to 98.0) on QTc interval.
  
  
  
  Using conventional doses during acute treatment in children with ASD and serious behavioral problems, there was no difference in the mean change in QTc between risperidone and placebo. Compared to the electrophysiologist, the machine readings may miss elevated QTc measurements.
authors.affiliation: 1 Department of Psychiatry, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Lan Chi
authors.initials: LC
authors.lastname: Vo
authors.affiliation: 2 Division of Pediatric Cardiology, University Hospitals Rainbow Babies and Children's Hospital , Cleveland, Ohio.
authors.forename: Christopher
authors.initials: C
authors.lastname: Snyder
authors.affiliation: 3 Children's Hospital of Atlanta & Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Courtney
authors.initials: C
authors.lastname: McCracken
authors.affiliation: 4 Harvard Medical School, Massachusetts General Hospital, Lurie Center for Autism , Boston, Massachusetts.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McDougle
authors.affiliation: 5 Division of Child Psychiatry, University of California at Los Angeles , Los Angeles, California.
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.affiliation: 6 Nisonger Center, Ohio State University , Columbus, Ohio.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Aman
authors.affiliation: 7 Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Tierney
authors.affiliation: 6 Nisonger Center, Ohio State University , Columbus, Ohio.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: 8 Mattel Children's Hospital, University of California at Los Angeles , Los Angeles, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levi
authors.affiliation: 3 Children's Hospital of Atlanta & Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Michael
authors.initials: M
authors.lastname: Kelleman
authors.affiliation: 9 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Carroll
authors.affiliation: 8 Mattel Children's Hospital, University of California at Los Angeles , Los Angeles, California.
authors.forename: John
authors.initials: J
authors.lastname: Morrissey
authors.affiliation: 10 National Institute of Mental Health , Bethesda, Maryland.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.affiliation: 11 Marcus Autism Center, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Lawrence
authors.initials: L
authors.lastname: Scahill
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000067877:Autism Spectrum Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone
keywords: QTc; autism spectrum disorder; cardiac conduction; electrocardiogram; risperidone