antagonising the effect
of bright light.
This review aims to evaluate whether melatonin taken by mouth can prevent or alleviate jet-lag
associated with air
travel across several time zones. The review also examines the evidence for the effectiveness of
Airline passengers, airline staff or military personnel.
Oral melatonin, compared with placebo or other medication, taken before during and/or after travel.
The primary outcome measure is subjective rating of jet-lag, and components or correlates of this,
fatigue, daytime tiredness, onset of sleep at destination, onset and quality of sleep, psychological
duration of return to normal, and measures indicating the phase of circadian rhythms.
See: Collaborative Review Group search strategy
We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and PsychLit
Citation Index was searched to identify trials that had cited the studies. The journals 'Aviation, Space
and Environmental Medicine' and 'Sleep' from 1986 -1999 were searched by hand, including the
conference abstracts published there. We searched citation lists of relevant studies for other relevant
trials. We asked principal authors of relevant studies to tell us about unpublished trials.
We also searched for reports of suspected adverse effects of melatonin that were not reported in the
studies retrieved in the above searches.
We checked Martindale 99, Meyler's Side Efects of Drugs (SED 96), and Side Effects of Drugs
Annuals (SEDA) up to vol 22 (1999);
searched 'Reactions Weekly' from 1990 to 1999, using the annual indexes to find all items
obtained the reports mentioning melatonin from the WHO Uppsala Monitoring Centre and the US
and searched MEDLINE using the MESH term 'Melatonin-adverse effects'.
We did not search EMBASE because that is used in the production of SED and SEDA.
All relevant RCTs were considered and the full reports obtained, as was subsequent published
them. Several authors were contacted and asked for supplementary information.
The trials that met the inclusion criteria are referred to in this review by the year of publication
followed by the first author's name, eg '87 Arendt', except when they are mentioned informally in the
text. This has been done so that they can be listed in chronological order in the Table of
characteristics of included studies, to make it easier for readers to see how the design of the studies
has developed over the years. The other references are cited and listed in the conventional style.
*Quality assessment: allocation concealment and blinding was looked for, described and evaluated
Methods of measurement used in the trials are described and their relevance, validity and
*Data were extracted independently by each author; differences were reconciled
*Data synthesis: the following comparisons are made -
(1) melatonin v. placebo;
(2) treatment with melatonin only after arrival at destination ('post' regimen) v. treatment before,
during and after travel ('pre+post' regimen);
(3) eastward flights v. westward flights (with placebo and with melatonin);
(4) passengers v. airline staff v. military personnel;
(5a) low doses (5mg or less) v. high (8mg or more);
(5b) low doses v. very low doses (0.5mg);
(5c) rapid-release melatonin v. slow-release melatonin;
(6) short (48 hr or less) v. long (over 48 hr) treatment.
A meta-analysis was performed of visual analogue scores of jet-lag symptoms from 5 trials that were
sufficiently similar in design.
Adverse events noted in the course of the trials are summarised and assessed.
Reports of adverse events linked with melatonin in other contexts, i.e. outside RCTs, were screened.
Those that were considered potentially relevant to the use of melatonin for jet-lag are summarised
and evaluated. To be considered potentially relevant, reports had to be related to use of melatonin for
14 days or less, or use for jet-lag, and to include enough contextual information about the event to
raise reasonable suspicion that melatonin might have contributed to it.
Description of studies
Nine trials, published between 1986 and 1999, met the inclusion criteria. All compared melatonin
One study, in US soldiers on an overseas rapid deployment mission, was excluded because it tested
their adaptation to night operations at the destination in the Middle East, and not adaptation to the
new time zone (Comperatore 96).
One trial (93 Petrie) directly compared a 'pre+post' with an 'post' regimen, in airline cabin staff who