DRUGS TO TREAT JET LAG SLEEP DISORDER
Melatonin appears safe
Most field studies have found that nightly doses of melatonin (2–8 mg) improve the quality of sleep30–32 or alleviate daytime symptoms of jet lag, or both.20,30,31,33–36 Immediate-release preparations appear to be more effective than slow-release ones.31 Although most studies looked exclusively at adaptation to eastward travel,30–32,35,36 one studied westward travel,33 and another assessed melatonin’s effects during both departure and return trips that traversed 11 time zones.34
In studies of preflight dosing, melatonin was scheduled for up to 3 days before departure (and en route in two instances),30,34 at clock hours corresponding to the nocturnal sleep period at the travel destination (consistent times daily), and then for a subsequent 3 to 4 days between a destination time of 22:00 and 00:00 hours (ie, at bedtime).30,31,34–36 Several other studies further simplified this regimen, with participants taking nocturnal melatonin only on arrival at the destination, either for eastward31,32 or for westward travel.33
The study involving solely westward travel (Los Angeles to New Zealand) was the only one of the studies with positive findings that allowed for comparisons between participants who received melatonin before departure (3 days at 5-mg doses, taken between 07:00 and 08:00 Los Angeles time) and continuing for 5 days after arrival at 22:00 to 00:00 New Zealand time, and those who received melatonin beginning only on arrival.33 Significantly better jet lag outcomes were found in the latter group.
An important caveat is that melatonin is sold over the counter as a nutritional supplement and is not regulated by the United States Food and Drug Administration (FDA), so verification of purity of the product is difficult.
A comprehensive review by the National Academy of Sciences stated that, given the available data, short-term use of melatonin in total daily doses of 10 mg or less in healthy adults appears to be safe.37
Benzodiazepine receptor agonists improve sleep, but maybe not sleepiness
The use of standard hypnotics during periods of circadian realignment appears to be commonplace but has not been well studied.20 Trials of the newer benzodiazepine receptor agonists—three studies of zolpidem (Ambien) 10 mg30,38,39 and two of zopiclone 5 to 7.5 mg32,40—found consistently favorable subjective30,38 and objective32,39,40 outcomes in counteracting jet-lag-induced insomnia (for both eastward and westward travel). (Note: Zopiclone is not available in the United States, but its enantiomer eszopiclone [Lunesta] is.) However, the evidence is less clear for daytime symptoms of jet lag, with outcomes reported as favorable,30 equivocal,40 or inaccessible.32,38,39
The discrepancy between studies incorporating systematic daytime assessments may be due to differential medication effects (zolpidem vs zopiclone).
In two studies that compared these standard hypnotics to oral melatonin, one found that zopiclone 5 mg and melatonin 2 mg were equally beneficial with respect to sleep variables (other jet lag symptoms were not assessed).32 In another study, zolpidem 10 mg was superior to melatonin 5 mg for sleep and other jet lag symptoms, and the combination of zolpidem and melatonin was no better than zolpidem alone.30
Importantly, however, adverse effects were more frequent in those taking zolpidem and included nausea, vomiting, and confusion.30 Although these effects were not deemed serious, 14 participants (10%) withdrew from the study.
Caffeine is commonly used to combat the sleepiness of jet lag, but only two controlled field studies have assessed its efficacy.41,42 Both used slow-release preparations at a daily dosage of 300 mg.
In one study, after an eastward flight traversing seven time zones, participants took the pill at 08:00 destination time every day for 5 days.41 Curiously, alertness and other jet lag symptoms were not assessed, but circadian rhythms (determined by levels of cortisol in saliva) were re-entrained at a more rapid rate with caffeine than with placebo, and to a degree comparable with that achieved by exogenous melatonin.
In a follow-up study by the same group, those receiving caffeine were objectively less sleepy (as assessed by multiple sleep latency tests) than those taking melatonin or placebo, but subjective differences between groups were not identified.42 Furthermore, those taking caffeine had significantly more nocturnal sleep complaints, as assessed both objectively and subjectively.
A recent randomized, double-blind, placebo-controlled trial of the stimulant armodafinil (Nuvigil) found less sleepiness on multiple sleep latency testing and a decrease in jet leg symptoms with a dosage of 150 mg than with placebo.43
SHIFT WORK SLEEP DISORDER: DEFINITION, PREDISPOSING FACTORS
Shift work refers to nonstandard work schedules, including on-call duty, rotating shifts, and permanent night work. In the United States, one in five workers works a nonstandard shift.20
While shift work presents obvious difficulties, the diagnosis of shift work sleep disorder is reserved for those who have chronic insomnia or sleepiness at times that are not conducive to the externally demanded sleep-wake schedule, despite having the opportunity for sufficient daytime sleep.1 When defined in such a fashion, this disorder may afflict nearly a third of workers,44 with potential adverse effects on safety, health, and quality of life.
Older age is considered a risk factor for intolerance to shift work.20 In a study of physiologic phase shifts in response to night work, older workers were less able to recover after several night shifts.45 A large survey of police officers working the night shift supported the finding of more sleep disruption and on-duty sleepiness in older people.46