Diane C Chugani1, Harry T Chugani2, Max Wiznitzer3, Sumit Parikh4, Patricia A Evans5, Robin L Hansen6, Ruth Nass7, James J Janisse8, Pamela Dixon-Thomas9, Michael Behen10, Robert Rothermel11, Jacqueline S Parker10, Ajay Kumar12, Otto Muzik12, David J Edwards13, Deborah Hirtz14. 1. Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI; Children's Hospital of Michigan, Detroit, MI. Electronic address: Diane.Chugani@nemours.org. 2. Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI; Children's Hospital of Michigan, Detroit, MI; Department of Neurology, Wayne State University School of Medicine, Detroit, MI. 3. Neuroscience Institute, University Hospitals Case Medical Center, Rainbow Babies and Children's Hospital, Cleveland, OH. 4. Cleveland Clinic Neurogenetics & Metabolism, Neuroscience Institute Lerner College of Medicine-Case Western Reserve University, Cleveland, OH. 5. Departments of Neurology and Pediatrics, University of Texas Southwestern Medical Center, Children's Medical Center of Dallas, Dallas, TX. 6. Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, Department of Pediatrics, University of California Davis, Davis, CA. 7. Department of Neurology, New York University Langone Medical Center, New York, NY; Department of Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, NY. 8. Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI. 9. Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI. 10. Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI; Children's Hospital of Michigan, Detroit, MI. 11. Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI. 12. Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI; Children's Hospital of Michigan, Detroit, MI; Department of Neurology, Wayne State University School of Medicine, Detroit, MI; Department of Radiology, Wayne State University School of Medicine, Detroit, MI. 13. School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada. 14. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
Abstract
OBJECTIVES: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). STUDY DESIGN:Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. RESULTS: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. CONCLUSIONS: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00873509.
RCT Entities:
OBJECTIVES: To determine safety and efficacy of the 5HT1Aserotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). STUDY DESIGN:Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. RESULTS: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. CONCLUSIONS: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00873509.
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