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. 2008 Dec 4;2008:2303.

Jet lag

Andrew Herxheimer 1
PMCID: PMC2907932  PMID: 19445780

Abstract

Introduction

Jet lag is a syndrome caused by disruption of the "body clock", and affects most air travellers crossing five or more time zones; it tends to be worse on eastward than on westward flights.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent or minimise jet lag? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found five systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: hypnotics, lifestyle and environmental adaptations, and melatonin.

Key Points

Jet lag is a syndrome associated with rapid long-haul flights across several time zones, characterised by sleep disturbances, daytime fatigue, reduced performance, gastrointestinal problems, and generalised malaise.

  • It is caused by a disruption of the "body clock", which gradually adapts under the influence of light and dark, mediated by melatonin secreted by the pineal gland: darkness switches on melatonin secretion; exposure to strong light switches it off.

  • The incidence and severity of jet lag increase with the number of time zones crossed; it tends to be worse on eastward than on westward flights.

Melatonin reduces subjective ratings of jet lag on eastward and on westward flights compared with placebo.

  • The adverse effects of melatonin have not been systematically studied, but people with epilepsy and people taking an oral anticoagulant should probably not use it without medical supervision.

Hypnotics (zopiclone or zolpidem), taken before bedtime on the first few nights after flying, may reduce the effects of jet lag by improving sleep quality and duration but not other components of jet lag.

  • Hypnotics are associated with various adverse effects, including headache, dizziness, nausea, confusion, and amnesia, which may outweigh any short-term benefits.

We found no studies that examined the effectiveness of lifestyle or environmental adaptations (such as eating, avoiding alcohol or caffeine, sleeping, daylight exposure, or arousal).

  • After a westward flight, it is worth staying awake while it is daylight at the destination and trying to sleep when it gets dark. After an eastward flight, one should stay awake but avoid bright light in the morning, and be outdoors as much as possible in the afternoon. This will help to adjust the body clock and turn on the body's own melatonin secretion at the right time.

About this condition

Definition

Jet lag is a syndrome associated with rapid long-haul flights across several time zones, characterised by sleep disturbances, daytime fatigue, reduced performance, gastrointestinal problems, and generalised malaise. As with most syndromes, not all of the components must be present in any one case. It is caused by the "body clock" continuing to function in the day–night rhythm of the place of departure. The rhythm adapts gradually under the influence of light and dark, mediated by melatonin secreted by the pineal gland: darkness switches on melatonin secretion; exposure to strong light switches it off.

Incidence/ Prevalence

Jet lag affects most air travellers crossing five or more time zones. The incidence and severity of jet lag increase with the number of time zones crossed.

Aetiology/ Risk factors

Someone who has previously experienced jet lag is liable to do so again. Jet lag worsens with the more time zones crossed in one flight, or series of flights, within a few days. Westward travel generally causes less disruption than eastward travel as it is easier to lengthen, rather than to shorten, the natural circadian cycle.

Prognosis

Jet lag is worst immediately after travel and gradually resolves over 4 to 6 days as the person adjusts to the new local time. The more time zones crossed, the longer it takes to wear off.

Aims of intervention

To prevent or minimise jet lag, with minimal adverse effects.

Outcomes

Severity of jet lag, including subjective jet lag score and daytime alertness; Sleep quality and duration; Adverse effects of treatment.

Methods

Clinical Evidence search and appraisal June 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to June 2008, Embase 1980 to June 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 2 (1966 to date of issue). An additional search was carried out of the NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single-blinded, and containing more than 20 people of whom more than 80% were followed up. The minimum length of follow-up required to include studies was 3 days, as jet lag fades rapidly and rarely lasts longer than 5 days. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. This review includes studies whose purpose was the prevention of jet lag, in which interventions may have been given before or after travelling. RCTs were included only if the author described the basis of their definition of jet lag, even if not all components of the syndrome were looked for or documented. To aid readability of the numerical data in our reviews, we round percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Jet lag.

Important outcomes Severity of jet lag, Sleep quality
Studies (Participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of interventions to prevent or minimise jet lag?
10 (975) Severity of jet lag Melatonin versus placebo 4 0 –1 –1 0 Low Consistency point deducted for conflicting results. Directness point deducted for non-standardised formulation of melatonin
1 (52) Severity of jet lag Melatonin after arrival versus placebo 4 –1 0 –2 0 Very low Quality point deducted for sparse data. Directness points deducted for non-standardised formulation of melatonin and narrow population
1 (52) Sleep quality Melatonin after arrival versus placebo 4 –1 0 –2 0 Very low Quality point deducted for sparse data. Directness points deducted for non-standardised formulation of melatonin and narrow population
1 (52) Severity of jet lag Melatonin before and after arrival versus placebo 4 –1 0 –2 0 Very low Quality point deducted for sparse data. Directness points deducted for non-standardised formulation of melatonin and narrow population
2 (170) Severity of jet lag Hypnotics versus placebo 4 –1 –1 –1 0 Very low Quality point deducted for sparse data. Consistency point deducted for conflicting results. Directness point deducted for narrow inclusion criteria in one RCT
3 (303) Sleep quality Hypnotics versus placebo 4 0 0 –1 0 Moderate Directness point deducted for narrow inclusion criteria in one RCT
1 (137) Severity of jet lag Zolpidem plus melatonin versus placebo 4 –1 –1 0 0 Low Quality point deducted for sparse data. Consistency point deducted for conflicting results
1 (137) Sleep quality Zolpidem plus melatonin versus placebo 4 –1 0 0 0 Moderate Quality point deducted for sparse data
1 (137) Sleep quality Zolpidem plus melatonin versus zolpidem alone 4 –1 0 –1 0 Low Quality point deducted for sparse data. Directness point deducted for narrow inclusion criteria
1 (20) Severity of jet lag Different types of artificial light exposure versus each other 4 –1 0 0 0 Moderate Quality point deducted for sparse data
1 (20) Sleep quality Different types of artificial light exposure versus each other 4 –1 0 0 0 Moderate Quality point deducted for sparse data
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We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

  • 1.Herxheimer A, Waterhouse J. The prevention and treatment of jet lag. BMJ 2003;326:296–297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. In: The Cochrane Library, Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd. Search date 1999. Primary sources Cochrane Controlled Trials Register, Medline, Embase, Psychlit, Science Citation Index, hand searches of relevant journals, and contact with authors. A systematic search for harms of melatonin outside randomised trials was also made. [DOI] [PubMed] [Google Scholar]
  • 3.Daurat A, Benoit O, Buguet A. Effects of zopiclone on the rest/activity rhythm after a westward flight across five time zones. Psychopharmacology 2000;149:241–245. [DOI] [PubMed] [Google Scholar]
  • 4.Jamieson AO, Zammit GK, Rosenberg RS, et al. Zolpidem reduces the sleep disturbance of jet lag. Sleep Med 2001;2:423–430. [DOI] [PubMed] [Google Scholar]
  • 5.Suhner A, Schlagenhauf P, Hofer I, et al. Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag. Aviat Space Environ Med 2001;72:638–646. [PubMed] [Google Scholar]
  • 6.Boulos Z, Macchi MM, Sturchler MP, et al. Light visor treatment for jet lag after westward travel across six time zones. Aviat Space Environ Med 2002;73:953–963. [PubMed] [Google Scholar]
  • 7.Waterhouse JM, Minors DS, Waterhouse ME, et al. Keeping in time with your body clock. Oxford, UK: Oxford University Press, 2002. [Google Scholar]
BMJ Clin Evid. 2008 Dec 4;2008:2303.

Melatonin

Summary

Melatonin reduces subjective ratings of jet lag on eastward and on westward flights, compared with placebo.

Melatonin has been associated with possible adverse effects, and its pharmacology and toxicology are unclear. People with epilepsy or taking warfarin (or another oral anticoagulant) should not use melatonin without medical supervision.

Routine pharmaceutical quality control of melatonin products is necessary.

Benefits and harms

Melatonin versus placebo:

We found one systematic review (search date 1999, 10 RCTs, 975 people) comparing melatonin versus placebo. Nine RCTs included in the review were in air travellers, and one was in international airline cabin staff. In the RCTs, melatonin was given in a varying combination of: before the flight, on the day of the flight, and after the flight. Four RCTs reported global jet lag scores that could be combined.

Severity of jet lag

Melatonin compared with placebo Melatonin may be more effective than placebo at reducing jet lag scores after eastward and westward flights (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Jet lag score

Systematic review		 142 travellers on eastward flights
4 RCTs in this analysis		 Weighted mean subjective jet lag score
30.9 with melatonin
50.7 with placebo
WMD –19.5
95% CI –28.1 to –10.9 		Effect size not calculated melatonin

Systematic review		 90 travellers on westward flights
2 RCTs in this analysis		 Weighted mean subjective jet lag score
22.3 with melatonin
40.6 with placebo
WMD –17.3
95% CI –27.3 to –7.3 		Effect size not calculated melatonin
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Sleep quality

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 Travellers on eastward and westward flights
10 RCTs in this analysis		 Adverse effects
with melatonin
with placebo
Absolute results not reported
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Melatonin after arrival versus placebo:

One RCT included in the review (52 international airline cabin crew completing a 9-day tour of duty) compared melatonin after arrival, and melatonin before and after arrival, versus placebo.

Severity of jet lag

Melatonin compared with placebo Melatonin after arrival may be no more effective than placebo at reducing jet lag scores after flights (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Jet lag score

Systematic review		 52 international airline cabin crew completing a 9-day tour of duty
Data from 1 RCT		 Jet lag
with melatonin after arrival
with placebo
P <0.005
The review noted that it is difficult to generalise from this finding because the airline staff had complex disordered circadian rhythms due to rapidly repeated flights 		Effect size not calculated melatonin after arrival
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Sleep quality

Melatonin compared with placebo Melatonin after arrival may be more effective than placebo at improving sleep quality after flights (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Sleep disturbance

Systematic review		 52 international airline cabin crew completing a 9-day tour of duty
Data from 1 RCT		 Sleep disturbance
with melatonin after arrival
with placebo
Absolute results not reported
P <0.01
The review noted that it is difficult to generalise from this finding because the airline staff had complex disordered circadian rhythms due to rapidly repeated flights 		Effect size not calculated melatonin after arrival
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Adverse effects

No data from the following reference on this outcome.

Melatonin before and after arrival versus placebo:

One RCT included in the review (52 international airline cabin crew completing a 9-day tour of duty) compared melatonin after arrival, and melatonin before and after arrival, versus placebo.

Severity of jet lag

Melatonin compared with placebo We don’t know whether melatonin before and after arrival is more effective than placebo at reducing the severity of jet lag after flights (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Severity of jet lag

Systematic review		 52 international airline cabin crew completing a 9-day tour of duty
Data from 1 RCT		 Overall recovery
with melatonin before and after arrival
with placebo
Absolute results not reported
Significance not assessed
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Sleep quality

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 52 international airline cabin crew completing a 9-day tour of duty Adverse effects
with melatonin before and after arrival
with placebo
Melatonin has been associated with neurological and gastrointestinal adverse effects; see further information on studies for full details
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Melatonin plus zolpidem:

See option on hypnotics.

Further information on studies

The review reported that melatonin reduced the symptoms of jet lag in eight RCTs, whereas two RCTs found no effect on symptoms between melatonin and placebo (see comment).

The adverse effects of melatonin have not yet been adequately investigated (see comment). One RCT found no significant difference between melatonin and placebo in adverse effects; another found that a disorientating "rocking" feeling was significantly more frequent with melatonin (P = 0.036). Hypnotic effects after melatonin occurred in five RCTs, affecting about 10% of people (further details not reported). Other effects included headache or heavy head (2 RCTs); disorientation (1 RCT); ear, nose, and throat problems; nausea; and gastrointestinal problems (absolute numbers not reported; P values not reported). One person had difficulty in swallowing and breathing within 20 minutes of taking melatonin. Symptoms subsided after 45 minutes. They recurred after a further dose of melatonin. The review reported that the adverse events in the trials occurred during treatment and seemed to have been short-lived. The review noted that the pharmacology and toxicology of melatonin had not been systematically studied. It found six published and 19 unpublished case reports of possible related adverse effects on the central nervous system (including confusion, ataxia, headache, and convulsant effects), blood clotting (prothrombin increased or decreased, suspected interaction with warfarin), cardiovascular system (including chest pain and dyspnoea), and skin (fixed drug eruption). Although it noted the difficulty of interpreting such data, it questioned the safety of melatonin in people with epilepsy and in people taking warfarin or other oral anticoagulants. It suggested that people in these groups should not use melatonin without an informed (medical) discussion, and concluded that further investigation was needed.

Comment

The trials reviewed did not state whether travellers were frequent flyers or not. Two RCTs found no effect on symptoms with melatonin. In the first of these RCTs, the review noted that there was probably insufficient time between inward and outward flights for participants to have fully adjusted to the new time zone. Hence, people may have suffered less jet lag on the return flight than might be expected, making it harder to detect effects. In the second RCT, the data suggested that melatonin may have reduced jet lag after 3 days, but the statistical analysis in the RCT did not test this. One RCT reported details of the source of melatonin; most did not state the pharmaceutical form used. Some melatonin products have been found to contain unidentified impurities. The review concluded that "the pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established".

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Dec 4;2008:2303.

Hypnotics

Summary

Hypnotics (zopiclone or zolpidem), taken before bedtime on the first few nights after flying, may reduce the effects of jet lag by improving sleep quality and duration but not other components of jet lag.

Hypnotics are associated with adverse effects including headache, dizziness, nausea, confusion, and amnesia. Short-term benefits of hypnotics must be considered in the light of potential adverse effects.

Benefits and harms

Hypnotics versus placebo:

We found no systematic review but found three RCTs.

Severity of jet lag

Hypnotics compared with placebo The effect of hypnotics (zopiclone and zolpidem) on severity of jet lag are unclear (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Severity of jet lag

RCT		 33 people, westward flight crossing 5 time zones Subjective jet lag scores (see comment) first, second, fifth, and sixth days after the flight
with zopiclone (taken 30 minutes before bedtime on the first 4 nights after the flight)
with placebo
Absolute results not reported
Not significant 		Not significant

RCT
4-armed trial 		137 people, eastward flight crossing 5–9 time zones Alleviating symptoms of jet lag (see comment) fourth day after the flight
with zolpidem alone taken during the flight and at bedtime for 4 consecutive days after the flight
with placebo
Absolute results not reported
P <0.05 		Effect size not calculated zolpidem alone
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No data from the following reference on this outcome.

Sleep quality

Hypnotics compared with placebo Hypnotics (zopiclone and zolpidem) are more effective than placebo at improving sleep duration and quality (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Sleep quality

RCT		 33 people, westward flight crossing 5 time zones Sleep duration 2 nights after the flight
with zopiclone (taken 30 minutes before bedtime on the first 4 nights after the flight)
with placebo
Absolute results not reported
P <0.05 		Effect size not calculated zopiclone

RCT		 33 people, westward flight crossing 5 time zones Sleep duration 3 nights after the flight
with zopiclone (taken 30 minutes before bedtime on the first 4 nights after the flight)
with placebo
Absolute results not reported
P <0.01 		Effect size not calculated zopiclone

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Mean number of awakenings the first 2 nights after the flight
with zolpidem (taken immediately before bedtime on the first 3 nights after the flight)
with placebo
Absolute results not reported
P <0.05 		Effect size not calculated zolpidem

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Sleep quality (measured using a 4-point rating scale) the first 3 nights after the flight
with zolpidem (taken immediately before bedtime on the first 3 nights after the flight)
with placebo
Absolute results not reported
P <0.05 		Effect size not calculated zolpidem

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Overall self-rated sleep quality (measured using a 5-point rating scale) during the flight
with zolpidem alone taken during the flight and at bedtime for 4 consecutive days after the flight
with placebo
P <0.05 		Effect size not calculated zolpidem alone
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Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Headache
12/68 (18%) with zolpidem
6/65 (9%) with placebo

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Rhinitis
2/68 (3%) with zolpidem
1/65 (2%) with placebo

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Diarrhoea
2/68 (3%) with zolpidem
1/65 (2%) with placebo

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Abnormal dreaming
2/68 (3%) with zolpidem
0/65 (0%) with placebo

RCT		 133 people aged 25–65 years who had travelled overseas at least twice during the past 24 months, eastward flights crossing 5–9 time zones Sinusitis
0/68 (0%) with zolpidem
2/65 (3%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Number of people with adverse effects
6/34 (18%) with zolpidem
3/39 (8%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Nausea
4/34 (12%) with zolpidem
1/39 (3%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Vomiting
2/34 (6%) with zolpidem
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Confusion
2/34 (6%) with zolpidem
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Dizziness
1/34 (3%) with zolpidem
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Headache
1/34 (3%) with zolpidem
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Palpitations
1/34 (3%) with zolpidem
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Sweating
0/34 (0%) with zolpidem
1/39 (3%) with placebo		 Effect size not calculated

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Dry mouth
1/34 (3%) with zolpidem
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Incapacitation
0/34 (0%) with zolpidem
0/39 (0%) with placebo
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No data from the following reference on this outcome.

Zolpidem plus melatonin versus placebo:

We found no systematic review but found one RCT.

Severity of jet lag

Zolpidem plus melatonin compared with placebo Zolpidem plus melatonin may be no more effective at reducing the symptoms of jet lag (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Severity of jet lag

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Alleviating symptoms of jet lag (see comment) fourth day after the flight
with zolpidem plus melatonin during the flight and at bedtime for 4 consecutive days after the flight
with placebo
Absolute results not reported
Reported as not significant 		Not significant
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Sleep quality

Zolpidem plus melatonin compared with placebo Zolpidem plus melatonin may be more effective than placebo at improving sleep quality during an eastward flight crossing 6–9 time zones (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Sleep quality

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Overall self-rated sleep quality (measured using a 5-point rating scale) during the flight
with zolpidem plus melatonin during the flight and at bedtime for 4 consecutive days after the flight
with placebo
Absolute results not reported
P <0.05 		Effect size not calculated zolpidem plus melatonin
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Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Number of people with adverse effects
7/29 (24%) with zolpidem plus melatonin
3/39 (8%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Nausea
4/29 (14%) with zolpidem plus melatonin
1/39 (3%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Vomiting
2/29 (7%) with zolpidem plus melatonin
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Confusion
4/29 (14%) with zolpidem plus melatonin
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Dizziness
2/29 (7%) with zolpidem plus melatonin
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Headache
2/29 (7%) with zolpidem plus melatonin
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Palpitations
0/29 (0%) with zolpidem plus melatonin
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Sweating
1/29 (3%) with zolpidem plus melatonin
1/39 (3%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Dry mouth
1/29 (3%) with zolpidem plus melatonin
0/39 (0%) with placebo

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Incapacitation
1/29 (3%) with zolpidem plus melatonin
0/39 (0%) with placebo
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No data from the following reference on this outcome.

Zolpidem plus melatonin versus zolpidem alone:

We found no systematic review but found one RCT.

Sleep quality

Zolpidem alone compared with zolpidem plus melatonin Zolpidem alone and zolpidem plus melatonin may be equally effective at improving sleep quality and duration (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Sleep quality

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Overall self-rated sleep quality (measured using a 5-point rating scale) during the flight
with zolpidem plus melatonin during the flight and at bedtime for 4 consecutive days after the flight
with zolpidem alone during the flight and at bedtime for 4 consecutive days after the flight
Absolute results not reported
Reported as not significant 		Not significant
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Severity of jet lag

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Number of people with adverse effects
7/29 (24%) with zolpidem plus melatonin
6/34 (18%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Nausea
4/29 (14%) with zolpidem plus melatonin
4/34 (12%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Vomiting
2/29 (7%) with zolpidem plus melatonin
2/34 (6%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Confusion
4/29 (14%) with zolpidem plus melatonin
2/34 (6%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Dizziness
2/29 (7%) with zolpidem plus melatonin
1/34 (3%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Headache
2/29 (7%) with zolpidem plus melatonin
1/34 (3%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Palpitations
0/29 (0%) with zolpidem plus melatonin
1/34 (3%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Sweating
1/29 (3%) with zolpidem plus melatonin
0/34 (0%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Dry mouth
1/29 (3%) with zolpidem plus melatonin
1/34 (3%) with zolpidem alone

RCT
4-armed trial 		137 people, eastward flight crossing 6–9 time zones Incapacitation
1/29 (3%) with zolpidem plus melatonin
0/34 (0%) with zolpidem alone
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Further information on studies

The RCT assessed subjective jet lag scores using a 100 mm visual analogue scale; jet lag symptoms were described as: feeling tired at unusual times of the day, bad mood, feeling of ill-being, digestive problems, and absence of energy.

The RCT used a 100 mm visual analogue scale to assess the severity of jet lag symptoms and effectiveness of medication.

Comment

Clinical guide:

Disruption of sleep is a major component of jet lag, and hypnotics have been used to try to reduce it. The short-term benefit seems to be outweighed by the wide range of unpleasant effects, some of them common.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Dec 4;2008:2303.

Lifestyle and environmental adaptations (eating, avoiding alcohol or caffeine, sleeping, daylight exposure, arousal)

Summary

We don't know whether lifestyle or environmental adaptations (such as eating, avoiding alcohol or caffeine, sleeping, daylight exposure, or arousal) are effective as we found insufficient high-quality evidence.

After a westward flight, it is worth staying awake while it is daylight at the destination and trying to sleep when it gets dark. After an eastward flight, one should stay awake but avoid bright light in the morning, and be outdoors as much as possible in the afternoon. This will help to adjust the body clock and turn on the body's own melatonin secretion at the right time.

Benefits and harms

Lifestyle adaptions (eating, avoiding alcohol or caffeine, sleeping, daylight exposure, or arousal) versus no lifestyle adaptions:

We found no systematic review or RCTs looking at the lifestyle and environmental adaptations of eating, avoiding alcohol or caffeine, sleeping, daylight exposure, or arousal (i.e., doing interesting things such as sightseeing or visiting friends; see comment).

Different types of artificial light exposure versus each other:

We found one RCT (20 people age 21–34 years) comparing artificial bright white light via a head-mounted light visor versus artificial dim red light for 3 hours on the first 2 evenings after a westward flight crossing six time zones.

Severity of jet lag

Artificial bright white light compared with artificial dim red light Artificial bright white light for 3 hours each evening is no more effective than artificial dim red light at reducing the severity of jet lag after 2 days (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Severity of jet lag

RCT		 20 people aged 21–34 years, westward flight crossing 6 time zones Jet lag (rated subjectively) 2 days
with artificial bright white light via a head-mounted light visor on the first 2 evenings
with artificial dim red light for 3 hours on the first 2 evenings
Absolute results not reported
Reported as not significant 		Not significant

RCT		 20 people aged 21–34 years, westward flight crossing 6 time zones Salivary melatonin (to detect the onset of evening secretion) 2 days
with artificial bright white light via a head-mounted light visor on the first 2 evenings
with artificial dim red light for 3 hours on the first 2 evenings
Absolute results not reported
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Sleep quality

Artificial bright white light compared with artificial dim red light Artificial bright white light for 3 hours each evening seems no more effective than artificial dim red light at improving sleep quality after 2 days (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Sleep quality

RCT		 20 people aged 21–34 years, westward flight crossing 6 time zones Sleep quality (rated subjectively) 2 days
with artificial bright white light via a head-mounted light visor on the first 2 evenings
with artificial dim red light for 3 hours on the first 2 evenings
Absolute results not reported
Reported as not significant 		Not significant
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Adverse effects

No data from the following reference on this outcome.

Further information on studies

None.

Comment

RCTs on the effects of lifestyle and environmental adaptation are unlikely to be carried out.

Clinical guide:

There is much physiological and anecdotal evidence to support environmental adaptation. Light is the major external environmental cue that pushes the circadian phase towards the light–dark rhythm at the destination. Endogenous melatonin production by the pineal gland is switched on by darkness, normally at dusk, and is inhibited by bright light. After a westward flight, it is probably worth staying awake while it is daylight at the destination and trying to sleep when it gets dark; and, after an eastward flight, being awake but avoiding bright light in the morning, and being outdoors as much as possible in the afternoon. Such behaviour may adjust the body clock and turn on the body's own melatonin secretion at the right time. Other cues may reinforce the effect of light, such as eating modestly at the times that correspond to usual meal times, and taking comfortable exercise.

Substantive changes

No new evidence

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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