Lan Chi Vo1, Christopher Snyder2, Courtney McCracken3, Christopher J McDougle4, James T McCracken5, Michael G Aman6, Elaine Tierney7, L Eugene Arnold6, Daniel Levi8, Michael Kelleman3, Deirdre Carroll9, John Morrissey8, Benedetto Vitiello10, Lawrence Scahill11. 1. 1 Department of Psychiatry, Emory University School of Medicine , Atlanta, Georgia . 2. 2 Division of Pediatric Cardiology, University Hospitals Rainbow Babies and Children's Hospital , Cleveland, Ohio. 3. 3 Children's Hospital of Atlanta & Emory University School of Medicine , Atlanta, Georgia . 4. 4 Harvard Medical School, Massachusetts General Hospital, Lurie Center for Autism , Boston, Massachusetts. 5. 5 Division of Child Psychiatry, University of California at Los Angeles , Los Angeles, California. 6. 6 Nisonger Center, Ohio State University , Columbus, Ohio. 7. 7 Kennedy Krieger Institute , Baltimore, Maryland. 8. 8 Mattel Children's Hospital, University of California at Los Angeles , Los Angeles, California. 9. 9 Yale Child Study Center, Yale University School of Medicine , New Haven, Connecticut. 10. 10 National Institute of Mental Health , Bethesda, Maryland. 11. 11 Marcus Autism Center, Emory University School of Medicine , Atlanta, Georgia .
Abstract
OBJECTIVES: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
RCT Entities:
OBJECTIVES: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Authors: Gian Loreto D'Alò; Franco De Crescenzo; Laura Amato; Fabio Cruciani; Marina Davoli; Francesca Fulceri; Silvia Minozzi; Zuzana Mitrova; Gian Paolo Morgano; Franco Nardocci; Rosella Saulle; Holger Jens Schünemann; Maria Luisa Scattoni Journal: Health Qual Life Outcomes Date: 2021-01-25 Impact factor: 3.186