title: Daytime sleep and performance following a zolpidem and melatonin cocktail.
abstract: OBJECTIVE
  Pharmacologic enhancement of daytime sleep may help sustain optimal cognitive performance. At effective doses, zolpidem induces sleep but also impairs performance. Combining melatonin with low-dose zolpidem may promote daytime sleep without exacerbating performance impairments seen with high-dose zolpidem alone.
  
  
  METHODS
  Following an 8-hour undisturbed nighttime sleep period, 80 subjects (50 men, 30 women) were administered oral zolpidem 0, 5, 10, or 20 mg at 10:00 am (n = 20 per group) and then oral melatonin 0 or 5 mg at 10:30 am (thus, n = 10 per drug combination) in a double-blind randomized fashion. Subjects napped from 10:00 am to 11:30 am, at which time they were awakened and cognitive tests administered (Restricted Reminding, Paired-Associates, and Psychomotor Vigilance). A second nap ensued from 12:45 pm to 4:00 pm, followed immediately by further testing.
  
  
  RESULTS
  Melatonin 5 mg plus zolpidem 0 mg enhanced daytime sleep (P < .05) with no memory or performance impairment (P > .05). Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep (albeit nonsignificantly), but memory and vigilance were impaired (P < .05). Melatonin's sleep-promoting effects were not evident until the second nap.
  
  
  CONCLUSIONS
  No advantages to administering melatonin plus zolpidem "cocktails" were evident. Unlike zolpidem, melatonin 5 mg alone improved daytime sleep without impairing memory and vigilance. Functional coupling of sleep-inducing and memory-impairing effects may be specific to benzodiazepine-receptor agonists such as zolpidem, suggesting potential advantages to using melatonin in the operational environment. That melatonin's sleep-promoting effects were delayed for several hours presents a practical consideration that may limit melatonin's usefulness when daytime sleep periods cannot be reliably anticipated or planned in advance.
authors.affiliation: Department of Behavioral Biology, Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. nancy.wesensten@us.army.mil
authors.forename: Nancy Jo
authors.initials: NJ
authors.lastname: Wesensten
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Balkin
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reichardt
authors.forename: Mary A
authors.initials: MA
authors.lastname: Kautz
authors.forename: George A
authors.initials: GA
authors.lastname: Saviolakis
authors.forename: Gregory
authors.initials: G
authors.lastname: Belenky
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D002940:Circadian Rhythm; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D011939:Mental Recall / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012463:Saliva / Q000737:chemistry; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects; D000077334:Zolpidem
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem; D008550:Melatonin