Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment

Dev Med Child Neurol. 1998 Mar;40(3):186-92. doi: 10.1111/j.1469-8749.1998.tb15445.x.


Nine girls with Rett syndrome (mean age, 10.1 years) were monitored 24 hours a day over a period of 10 weeks using wrist actigraphy. Baseline sleep-wake patterns were assessed for 1 week. Subsequently, patients underwent a 4-week melatonin treatment period in a double-blind, placebo-controlled, crossover protocol that employed a 1-week washout between treatment trials. Melatonin doses ranged from 2.5 to 7.5 mg, based upon individual body weight. Baseline sleep quality was poor compared with healthy children. At baseline the group demonstrated a low sleep efficiency (mean [+/- SE], 68.0+/-3.9%), long sleep-onset latency (42.1+/-12.0 minutes), and a short and fragmented total sleep time (7.5+/-0.3 hours; 15+/-2 awakenings per night). Melatonin significantly decreased sleep-onset latency to (mean +/- SE) 19.1+/-5.3 minutes (P<0.05) during the first 3 weeks of treatment. While the variability of individual responsiveness was high, melatonin appeared to improve total sleep time and sleep efficiency in the patients with the worse baseline sleep quality. Finally, a 4-week administration of melatonin appears to be a safe treatment as no adverse side effects were detected, yet long-term effects of chronic melatonin use in pediatric patients are unknown at this time.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / therapeutic use
  • Antioxidants / therapeutic use*
  • Child
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Melatonin / therapeutic use*
  • Rett Syndrome / complications*
  • Seizures / drug therapy
  • Severity of Illness Index
  • Sleep Wake Disorders / complications*
  • Sleep Wake Disorders / diagnosis
  • Sleep Wake Disorders / drug therapy*
  • Wakefulness


  • Anticonvulsants
  • Antioxidants
  • Melatonin