Melatonin for the prevention and treatment of jet lag.

Background: Jet lag commonly affects air travelers 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. Objectives: To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet lag after air travel across several time zones. Search Strategy: 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 We asked principal authors of relevant studies to tell us about unpublished trials.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 randomized 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. Selection Criteria: Randomized 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. Main Results: Nine of the 10 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 the cochrane column Opher Caspi, MD PhD, is a research assistant professor in the Program in Integrative Medicine at the University of Arizona. (Altern Ther Health Med. 2004;10(2):60-63. ) CLINICAL SCENARIO An otherwise healthy middle-age businessman who lives in California is planning an important business trip to Europe next month. Concerned about being too fatigued when he arrives there, he asks whether you have any tips on how he can avoid jet lag. SEARCHING FOR AN EVIDENCE-BASED ANSWER Since medical decisions, whether diagnostic or therapeutic, are usually made within the specific context and particularities of the patient for whom evidence is being sought, the search for evidence must always start with the construction of a well-built clinical question that focuses on the specifics. These questions are typically: who is the patient? What is the specific health issue to be addressed? What is the range of intervention options considered? And what is the set of potential outcomes desired or to be avoided? In the above case, the patient is an otherwise healthy middle-age man who would like to avoid jet lag while traveling eastward across many time zones. Please note how this case differs from, for example, a person who is already experiencing jet lag, or one that is about to travel westward a relatively short distance. Some other parameters, such as the patient’s gender are likely to be inconsequential in this specific case, yet very important in other cases. Evidence-based medicine works best when the question includes just the important parameters. Too much specification could be a bit too confusing. The next step is to retrieve the existing body of knowledge that pertains to the specific question under consideration. To maximize yield, it is important to prioritize the search so that you consult only those sources that are likely to provide you with valuable information. Sometimes textbooks would be sufficient (for example, when you want to learn about the natural history of a disease or its differential diagnosis). However, for the latest evidence on the efficacy and effectiveness of various therapeutics it is advisable to search for a systematic review that summarizes the evidence qualitatively, or better still, a meta-analysis that summarizes it quantitatively. A quick search of the Cochrane database reveals a Cochrane review “Melatonin for the prevention and treatment of jet lag,” an abstract of which follows: