Melatonin for the prevention and treatment of jet lag

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Abstract
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 We asked principal authors of relevant studies to tell us about unpublished trials.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. 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. Melatonina para la prevención y tratamiento de la desadaptación horaria ("jet lag") : La desadaptación horaria ("jet lag") afecta con frecuencia a los que viajan en avión y cruzan varias zonas horarias. La misma es el resultado de que los ritmos internos del cuerpo se desajustan con el ciclo día-noche de la zona de destino. La melatonina es una hormona pineal que tiene una importante función en la regulación de los ritmos corporales y se ha utilizado como un fármaco para reajustar los mismos al mundo exterior. : Evaluar la efectividad de la melatonina oral administrada en diferentes regímenes de dosis para mejorar la desadaptación horaria ("jet lag") después de viajes en avión a través de varias zonas horarias. : Se hicieron búsquedas en el Registro Cochrane de Ensayos Controlados (Cochrane Controlled Trials Register), en MEDLINE, EMBASE, PsychLit y Science Citation Index electrónicamente, y manualmente en las revistas "Aviation, Space and Environmental Medicine" y "Sleep". Se hicieron búsquedas en las listas de referencias de los estudios pertinentes para obtener información sobre otros ensayos pertinentes. Se solicitó información sobre ensayos no publicados a los autores principales de los estudios pertinentes. Se buscaron de forma sistemática informes de eventos adversos vinculados al uso de la melatonina fuera del contexto de ensayos aleatorios en "Side Effects of Drugs" (SED) y SED Annuals, "Reactions Weekly", MEDLINE y las bases de datos de reacciones adversas de los fármacos del WHO Uppsala Monitoring Centre (UMC) y la Food & Drug Administration de los EE.UU. : Ensayos aleatorios en pasajeros de líneas aéreas, personal de las líneas aéreas o personal militar a los que se les administró melatonina oral, comparada con placebo u otra medicación. Las medidas de resultados debería consistir en clasificación subjetiva de desadaptación horaria o los componentes relacionados, tales como el bienestar, cansancio en horario diurno, comienzo y calidad del sueño, funcionamiento psicológico, duración del retorno a la normalidad o indicadores de los ritmos circadianos. : Diez ensayos cumplieron los criterios de inclusión. Todos compararon melatonina con placebo; uno, además, la comparó con un...