title: Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD.
  
  
  OBJECTIVE
  To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD.
  
  
  METHODS
  This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat.
  
  
  METHODS
  Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks.
  
  
  METHODS
  The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels.
  
  
  RESULTS
  After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, -13.7 to -4.6; P < .001), from a mean (SD) of 49.1 (24.3) to 40.2 (20.9). Moreover, the sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo (95% CI, -38.6 to -4.2; P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency (r = -0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study.
  
  
  CONCLUSIONS
  Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01638234.
authors.affiliation: Department of Pediatrics, Taipei City Hospital Renai Branch, Taipei, Taiwan2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan3School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yung-Sen
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, Yonghe Cardinal Tien Hospital, New Taipei City, Taiwan.
authors.forename: Ming-Hung
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Lee
authors.affiliation: Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yang-Shia
authors.initials: YS
authors.lastname: Dai
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Kuan-Hua
authors.initials: KH
authors.lastname: Chu
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Chi
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Yu-Tsan
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
authors.forename: Chun-An
authors.initials: CA
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Taipei City Hospital Renai Branch, Taipei, Taiwan.
authors.forename: Kong-Sang
authors.initials: KS
authors.lastname: Wan
authors.affiliation: Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan8Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan9Department of Medical Research, National Taiwan University Hospital.
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000097:blood; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003876:Dermatitis, Atopic / Q000097:blood / Q000150:complications*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D017286:Polysomnography; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects*; D012893:Sleep Wake Disorders / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002492:Central Nervous System Depressants; C054513:6-sulfatoxymelatonin; D007073:Immunoglobulin E; D008550:Melatonin