Daytime sleep and performance following a zolpidem and melatonin cocktail

Sleep. 2005 Jan;28(1):93-103. doi: 10.1093/sleep/28.1.93.

Abstract

Study objectives: 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.

Design and 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antioxidants / administration & dosage
  • Antioxidants / analysis
  • Antioxidants / pharmacology*
  • Circadian Rhythm*
  • Cognition / drug effects
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Melatonin / administration & dosage
  • Melatonin / analysis
  • Melatonin / pharmacology*
  • Mental Recall / drug effects
  • Psychomotor Performance / drug effects*
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Saliva / chemistry
  • Sleep / drug effects*
  • Wakefulness / drug effects
  • Zolpidem

Substances

  • Antioxidants
  • Drug Combinations
  • Hypnotics and Sedatives
  • Pyridines
  • Zolpidem
  • Melatonin