title: An open label trial of donepezil for enhancement of rapid eye movement sleep in young children with autism spectrum disorders.
abstract: BACKGROUND
  Rapid eye movement (REM) sleep is greatest in the developing brain, is driven by acetylcholine, and may represent a protected time for neuroplasticity. Recently published data from our lab observed that children with autism spent significantly less time in this state during a single night recording than did typically developing children and those with developmental delay without autism. The objective of this study was to determine whether or not donepezil can increase the REM % in children with diagnosed autism spectrum disorder (ASD) found to have REM % values of at least two standard deviations below expected for age.
  
  
  METHODS
  Five subjects found to have an ASD (ages 2.5-6.9 years) and demonstrated deficits in REM sleep compared with within-lab controls were enrolled in a dose finding study of donepezil. Each subject was examined by polysomnography for REM sleep augmentation after drug administration.
  
  
  RESULTS
  REM sleep as a percentage of Total Sleep Time was increased significantly and REM latency was decreased significantly after drug administration in all subjects. No other observed sleep parameter was changed significantly.
  
  
  CONCLUSIONS
  Donepezil can increase the amount of time that children with an ASD spend in the REM sleep state. A double-blind, placebo-controlled trial is needed to assess the association between REM sleep augmentation and learning, cognition, and behavior in such children.
authors.affiliation: Department of Pediatrics and Developmental Neuroscience, National Institute of Mental Health , Bethesda, Maryland 20892, USA. shu.buckley@nih.gov
authors.forename: Ashura Williams
authors.initials: AW
authors.lastname: Buckley
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sassower
authors.forename: Alcibiades J
authors.initials: AJ
authors.lastname: Rodriguez
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Jennison
authors.forename: Katherine
authors.initials: K
authors.lastname: Wingert
authors.forename: Jack
authors.initials: J
authors.lastname: Buckley
authors.forename: Audrey
authors.initials: A
authors.lastname: Thurm
authors.forename: Susumu
authors.initials: S
authors.lastname: Sato
authors.forename: Susan
authors.initials: S
authors.lastname: Swedo
mesh_terms: D001321:Autistic Disorder / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000188:drug therapy*; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000188:drug therapy*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018697:Nootropic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017286:Polysomnography; D012890:Sleep / Q000502:physiology; D012893:Sleep Wake Disorders / Q000175:diagnosis; D012895:Sleep, REM / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil