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 We asked principal authors of relevant studies to tell us about unpublished trials.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. An updating search was carried out on 12/2/2008 but no new studies were identified.
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 well being, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms.
Data collection and analysis
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.
Eight 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. The estimated number needed to treat (NNT) is 2, based on the only two trials that gave the necessary data. 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.
電子搜尋Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index,手動搜尋 journals ‘Aviation, Space and Environmental Medicine’和 ‘Sleep’ 搜尋相關研究的文獻是否有其他相關試驗.像主要作者詢問是否有未發布試驗資料.隨機試驗外的melatonin相關的副作用採系統竟搜索‘Side Effects of Drugs’ (SED)和SED Annuals, ‘Reactions Weekly’, MEDLINE, the WHO Uppsala Monitoring Centre (UMC)和美國食品藥品管理局的副作用資料庫
10個試驗符合那如條件.都比較melatonin 和安慰劑.其中一個還有與安眠藥zolpidem比較.有九個試驗品質合格,納入評估,另一個有設計缺失,不能納入. MEDLINE, 搜索‘Reactions Weekly’,和世界衛生組織UMC資料庫,已取得試驗外的melatonin相關的副作用
10個試驗中有八個發現, 在目的地預定睡覺時間(晚上10 – 12點)左右服用melatonin,可減少穿越5個以上時區後產生的時差. 每日melatonin 劑量介於0.5 – 5毫克的療效相當,但比起使用0.5毫克的受試者,使用5毫克的受試者較快入睡且睡眠品質較好. 使用5毫克以上療效更大. 2毫克緩釋melatonin相對較無療效,顯示快速達到最大血清藥量的melatonin療效較佳.只有兩個試驗提供的資料可估計益一需治數,估計值為 2, 經過時區越多,治療益處越大,西向航班益處較少.服用melatonin 的時間很重要.服藥時間不對,例如在一大早服用,會讓人想睡且延長適應時間.其他副作用發生率低. Melatonin可能有害於癲癇或使用warfarin的患者
Melatonin對預防和治療時差療效卓越,偶爾短期使用是安全的.應建議飛行經過五個以上時區的成人旅客使用,尤其是一大早到目的地的班機或之前有時差的旅客. 經過2 – 4個時區的旅客也可使用.需系統性研究探討melatonin的藥理學和毒性,也需對melatonin藥品有常規的品質檢測. Melatonin對癲癇患者的影響或可能與warfarin產生的交互作用,都有待研究
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌