Daytime sleep and performance following a zolpidem and melatonin cocktail.
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.
Wesensten
Nancy Jo
NJ
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
Balkin
Thomas J
TJ
Reichardt
Rebecca M
RM
Kautz
Mary A
MA
Saviolakis
George A
GA
Belenky
Gregory
G
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
D000975:Antioxidants; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem; D008550:Melatonin