: Jet-lag commonly affects air travellers who cross several time zones. It results
from the body's internal rhythms being out of step with the day-night cycle at the
destination. Melatonin is a pineal hormone that plays a central part in regulating
bodily rhythms and has been used as a drug to re-align them with the outside world.
: To assess the effectiveness of oral melatonin taken in different dosage regimens
for alleviating jet-lag after air travel across several time zones.
: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and
Science Citation Index electronically, and the journals 'Aviation, Space and Environmental
Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for
other relevant trials. We asked principal authors of relevant studies to tell us about
unpublished trials. Reports of adverse events linked to melatonin use outside randomised
trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals,
'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala
Monitoring Centre (UMC) and the US Food & Drug Administration.
: Randomised trials in airline passengers, airline staff or military personnel given
oral melatonin, compared with placebo or other medication. Outcome measures should
consist of subjective rating of jet-lag or related components, such as subjective
wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning,
duration of return to normal, or indicators of circadian rhythms.
: Ten trials met the inclusion criteria. All compared melatonin with placebo; one
in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate
quality to contribute to the assessment, one had a design fault and could not be used
in the assessment. Reports of adverse events outside trials were found through MEDLINE,
'Reactions Weekly', and in the WHO UMC database.
: Nine of the ten trials found that melatonin, taken close to the target bedtime at
the destination (10pm to midnight), decreased jet-lag from flights crossing five or
more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective,
except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses
above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release
melatonin suggests that a short-lived higher peak concentration of melatonin works
better. Based on the review, the number needed to treat (NNT) is 2. The benefit is
likely to be greater the more time zones are crossed, and less for westward flights.
The timing of the melatonin dose is important: if it is taken at the wrong time, early
in the day, it is liable to cause sleepiness and delay adaptation to local time. The
incidence of other side effects is low. Case reports suggest that people with epilepsy,
and patients taking warfarin may come to harm from melatonin.
: Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional
short-term use appears to be safe. It should be recommended to adult travellers flying
across five or more time zones, particularly in an easterly direction, and especially
if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time
zones can also use it if need be. The pharmacology and toxicology of melatonin needs
systematic study, and routine pharmaceutical quality control of melatonin products
must be established. The effects of melatonin in people with epilepsy, and a possible
interaction with warfarin, need investigation.