title: Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00873509.
authors.affiliation: 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.
authors.forename: Diane C
authors.initials: DC
authors.lastname: Chugani
authors.affiliation: 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.
authors.forename: Harry T
authors.initials: HT
authors.lastname: Chugani
authors.affiliation: Neuroscience Institute, University Hospitals Case Medical Center, Rainbow Babies and Children's Hospital, Cleveland, OH.
authors.forename: Max
authors.initials: M
authors.lastname: Wiznitzer
authors.affiliation: Cleveland Clinic Neurogenetics & Metabolism, Neuroscience Institute Lerner College of Medicine-Case Western Reserve University, Cleveland, OH.
authors.forename: Sumit
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Departments of Neurology and Pediatrics, University of Texas Southwestern Medical Center, Children's Medical Center of Dallas, Dallas, TX.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Evans
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, Department of Pediatrics, University of California Davis, Davis, CA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Hansen
authors.affiliation: 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.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nass
authors.affiliation: Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI.
authors.forename: James J
authors.initials: JJ
authors.lastname: Janisse
authors.affiliation: Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Pamela
authors.initials: P
authors.lastname: Dixon-Thomas
authors.affiliation: Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI; Children's Hospital of Michigan, Detroit, MI.
authors.forename: Michael
authors.initials: M
authors.lastname: Behen
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Robert
authors.initials: R
authors.lastname: Rothermel
authors.affiliation: Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI; Children's Hospital of Michigan, Detroit, MI.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: 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.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: 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.
authors.forename: Otto
authors.initials: O
authors.lastname: Muzik
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors.forename: Deborah
authors.initials: D
authors.lastname: Hirtz
mesh_terms: D000067877:Autism Spectrum Disorder / Q000188:drug therapy*; D002065:Buspirone / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D012701:Serotonin / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D017366:Serotonin Receptor Agonists; D012701:Serotonin; D002065:Buspirone