A benzodiazepine hypnotic facilitates adaptation of circadian rhythms and sleep-wake homeostasis to an eight hour delay shift simulating westward jet lag.
OBJECTIVE
To determine whether appropriately timed administration of a short-acting benzodiazepine hypnotic, which has proven effective in an animal model of jet lag, also facilitates adaptation of circadian rhythmicity and sleep-wake homeostasis in a human model of jet lag.


METHODS
Subjects participated in two double-blind, placebo-controlled studies of adaptation to an 8-hr delay shift of sleep-wake and dark-light cycles simulating westward travel. Each 9-day laboratory study began with a 3-day habituation period followed by a 24-hr study to obtain basal hormonal and sleep profiles (23:00-07:00). Subjects were then kept awake until 07:00 the next day and slept in darkness 07:00-15:00 for the next five 24-hr spans post-shift.


METHODS
N/A.


METHODS
6 normal, healthy men 24-31 years of age.


METHODS
Oral Triazolam (0.5 mg) or placebo given at 04:00 before the first shifted sleep/dark period (3 hours before bedtime) and at 07:00 (at bedtime) on days 2-5 post-shift.


RESULTS
Sleep recordings and 24-hr cortisol and growth hormone profiles were obtained at baseline and on the first, third, and fifth days post-shift. Global measures of treatment efficacy were calculated for multiple endpoints representing circadian rhythmicity and sleep-wake homeostasis. With placebo, the shift induced disturbances of sleep and hormonal secretion, and a gradual re-entrainment of circadian rhythmicity. Triazolam significantly facilitated adaptation by accelerating re-entrainment of circadian rhythms (chronobiotic effect) and normalizing markers of sleep/wake homeostasis (hypnotic effect).


CONCLUSIONS
Appropriately timed administration of a benzodiazepine hypnotic appears to facilitate the adaptation of both circadian rhythmicity and sleep-wake homeostasis to a shifted dark/sleep cycle. Compounds with combined chronobiotic/hypnotic properties may be useful in conditions of jet lag or night work.
Buxton
O M
OM
Department of Medicine, University of Chicago, Illinois 60637, USA.
Copinschi
G
G
Van Onderbergen
A
A
Karrison
T G
TG
Van Cauter
E
E
D000222:Adaptation, Physiological / Q000187:drug effects*; D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000187:drug effects*; D004311:Double-Blind Method; D013006:Growth Hormone / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D017286:Polysomnography; D020178:Sleep Disorders, Circadian Rhythm / Q000175:diagnosis / Q000188:drug therapy*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014229:Triazolam / Q000494:pharmacology* / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D014229:Triazolam; D013006:Growth Hormone; D006854:Hydrocortisone