title: Phase-dependent treatment of delayed sleep phase syndrome with melatonin.
abstract: OBJECTIVE
  Delayed sleep phase syndrome (DSPS) is a circadian-rhythm sleep disorder characterized by abnormally late sleep and wake times. Melatonin, taken in the evening, advances sleep and circadian phase in patients with DSPS. However, little is known about the most effective dose or time of administration. In the present study, we tested the effectiveness of melatonin to advance the timing of sleep and circadian phase in individuals with DSPS.
  
  
  METHODS
  Following baseline assessment of sleep and circadian phase, subjects were randomly assigned to 1 of 3 treatment groups. The administration of melatonin (0.3 or 3.0 mg) or placebo was double-blinded.
  
  
  METHODS
  All procedures were conducted on an outpatient basis.
  
  
  METHODS
  Thirteen subjects with DSPS, recruited via flyers, advertisements, and referrals from the Sleep Clinic, completed this study.
  
  
  METHODS
  Melatonin (0.3 or 3.0 mg) or placebo was administered between 1.5 and 6.5 hours prior to dim light melatonin onset for a 4-week period.
  
  
  RESULTS
  Both doses of melatonin advanced the circadian phase of endogenous melatonin. The magnitude of phase advance in dim-light melatonin onset correlated strongly with the time of melatonin administration, with earlier times being more effective (r2 = 0.94, P < .0001). Similar, though weaker, relationships were obtained between the timing of melatonin administration and changes in sleep time.
  
  
  CONCLUSIONS
  These results indicate that melatonin advances the circadian clock and sleep in patients with DSPS in a phase-dependent manner. This is the first study that reports a relationship between timing of melatonin administration and phase changes in patients with DSPS.
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Evanston, IL, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Mundey
authors.forename: Susan
authors.initials: S
authors.lastname: Benloucif
authors.forename: Krisztina
authors.initials: K
authors.lastname: Harsanyi
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Dubocovich
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Zee
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D020178:Sleep Disorders, Circadian Rhythm / Q000188:drug therapy*; D012894:Sleep Stages / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D008550:Melatonin