title: Melatonin improves sleep in children with epilepsy: a randomized, double-blind, crossover study.
abstract: OBJECTIVE
  Insomnia, especially maintenance insomnia, is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, crossover study to identify the effects of melatonin on sleep and seizure control in children with epilepsy.
  
  
  METHODS
  Eleven prepubertal, developmentally normal children aged 6-11 years with epilepsy were randomized by a software algorithm to receive placebo or a 9-mg sustained release (SR) melatonin formulation for four weeks, followed by a one-week washout and a four-week crossover condition. The pharmacy performed blinding; patients, parents, and study staff other than a statistician were blinded. The primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. The secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on electroencephalogram (EEG), and reaction time (RT) measures on psychomotor vigilance task (PVT). Statistical tests appropriate for crossover designs were used for the analysis.
  
  
  RESULTS
  Data were analyzed from 10 subjects who completed the study. Melatonin decreased sleep latency (mean difference, MD, of 11.4 min and p = 0.02) and WASO (MD of 22 min and p = 0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, slow-wave sleep duration and rapid eye movement (REM) latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin.
  
  
  CONCLUSIONS
  SR melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed, but the study was too small to allow any conclusions to be drawn in this regard.
authors: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: Sejal.Jain@cchmc.org.
authors: Sejal V
authors: SV
authors: Jain
authors: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: Paul S
authors: PS
authors: Horn
authors: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Pulmonology and Sleep Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: Narong
authors: N
authors: Simakajornboon
authors: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: Dean W
authors: DW
authors: Beebe
authors: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: Katherine
authors: K
authors: Holland
authors: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: Anna W
authors: AW
authors: Byars
authors: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: Tracy A
authors: TA
authors: Glauser
mesh_terms: D002648:Child; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000150:complications*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D017286:Polysomnography; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000209:etiology*
chemical_list: D003692:Delayed-Action Preparations; D006993:Hypnotics and Sedatives; D008550:Melatonin
keywords: EEG spikes; Natural supplement; Seizure frequency; Sleep architecture; Sleep latency; WASO