Treatment of circadian rhythm disorders--melatonin.

Melatonin has clear acute and delayed effects on sleep and circadian rhythms. Decrements in core temperature and alertness have been found at different times of day following low pharmacological and physiological doses of melatonin. When correctly timed, melatonin induces both phase advances and phase delays of the circadian system in humans. When timed to advance, the decrement in temperature and alertness and the degree of shift are closely related to dose. In both simulation and field studies, correctly timed melatonin can alleviate some of the problems of shiftwork and jet lag, notably enhancing sleep and alertness and hastening adaptation of rhythms to the imposed schedule. Performance effects and changes in sleep architecture need to be fully evaluated. The optimization of dose and formulation is also an area that requires further work. Whether or not recently developed melatonin analogs (72) will prove more or less useful than melatonin in adapting to phase shift remains to be seen. If incorrectly timed, melatonin has the potential to induce deleterious effects. While short-term studies indicate that it has very low toxicity, there are no long-term safety data. All of the studies reported here concern healthy adult volunteers and the use of a preparation licensed for human experimental use and available on a named patient basis on prescription. There are no data on uncontrolled preparations available over the counter in some countries. Its effects in pregnancy, interaction with other medications, and many other considerations remain to be addressed. Thus, while melatonin is useful in well-controlled conditions, the indiscriminate use of unlicensed preparations is not advisable.