title: Melatonin and zopiclone as pharmacologic aids to facilitate crew rest.
abstract: OBJECTIVE
  In response to mission imperatives, transport aircrews must often sleep at inappropriate circadian times resulting in inadequate sleep. This study was undertaken to determine whether either melatonin or zopiclone could facilitate early circadian sleep, and to assess whether either of these medications would result in a psychomotor performance decrement which would preclude their use in aircrew.
  
  
  METHODS
  Thirteen subjects from DCIEM completed a double-blind cross-over protocol. All subjects were assessed for psychomotor performance during 3 drug conditions (placebo, 10 mg melatonin, and 7.5 mg zopiclone), which were separated by one week. Each of these conditions involved 2 nights of sleep, back-to-back, with the first night being a normal circadian control sleep (23:00 h bedtime, arising at 06:45 h), and the second night being an early circadian drug sleep (drugs at 16:45 h, 17:00 h bedtime, arising at 23:45 h). All subjects were tested for psychomotor performance, on both nights of each of the 3 drug conditions, pre- and post-sleep. Further, during the early circadian drug night, all subjects were tested every hour after arising at 23:45 h (24:00 h until 07:00 h. At the beginning of each psychomotor test session, subjects were asked for their subjective levels of sleepiness and fatigue.
  
  
  RESULTS
  Relative to placebo (339.5 min) the subjects slept more on melatonin (370.2 min, p < 0.01), and zopiclone (373.3 min, p < 0.01). Performance in serial reaction time (SRT) task (p < 0.001), logical reasoning task (LRT) (p < 0.001), serial subtraction task (SST) (p < 0.02), and Multitask (MT) (p < 0.03) were impaired for all 3 drug conditions immediately on awakening, compared with pre-sleep performance, as a result of a sleep-inertia effect. With respect to the subjective data, sleep inertia effects were evident for sleepiness (p < 0.001), mental fatigue (p < 0.002), and physical fatigue (p < 0.05). For SRT, LRT, and SST, performance recovered to pre-sleep levels within 1.25 h of awakening, and for MT recovery occurred 2.25 h after awakening. There were no differences in performance or subjective measures between placebo, melatonin and zopiclone.
  
  
  CONCLUSIONS
  Both zopiclone and melatonin improved sleep relative to placebo. After sleep inertia, performance recovered to pre-sleep levels for all tasks and was sustained at that level throughout the balance of the testing period. There was no impact of melatonin or zopiclone on performance measures compared with placebo.
authors.affiliation: Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada. mpaul@dciem.dnd.ca
authors.forename: M A
authors.initials: MA
authors.lastname: Paul
authors.forename: G
authors.initials: G
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Buguet
authors.forename: G
authors.initials: G
authors.lastname: Gray
authors.forename: R A
authors.initials: RA
authors.lastname: Pigeau
authors.forename: H
authors.initials: H
authors.lastname: Weinberg
authors.forename: M
authors.initials: M
authors.lastname: Radomski
mesh_terms: D000328:Adult; D000337:Aerospace Medicine; D053961:Azabicyclo Compounds; D002170:Canada; D002940:Circadian Rhythm / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008875:Middle Aged; D008887:Military Medicine; D010879:Piperazines / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D013647:Task Performance and Analysis
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D008550:Melatonin