Jet lag—Jet lag, a disturbance of the sleep-wake cycle, occurs when there is a disparity between the external time, ie, hours of daylight or darkness, and the traveler’s endogenous circadian clock (internal time). The internal time regulates not only daily sleep rhythms but also body temperature and many metabolic systems. The synchronization of the circadian clock relies on light as the most potent “zeitgeber” (time giver).
Jet lag is especially common among frequent travelers and airplane cabin crews. Typical symptoms of jet lag may include daytime drowsiness, insomnia, frequent awakenings, and gastrointestinal upset. Clinical studies of melatonin have reported subjective reduction in daytime fatigue, improved mood, and a quicker recovery time (return to normal sleep patterns, energy, and alertness). These outcomes are also supported by a systematic review that showed melatonin was better than placebo in helping patients fall asleep faster and to sleep better at their destination. When traveling across five or more time zones, jet lag symptoms are reduced when taking melatonin close to the target bedtime (10 pm to midnight) at the new destination. The benefit of melatonin is thought to be greater as more time zones are crossed. In addition, melatonin appears more effective for eastbound travel than for westward travel. Finally, maximizing exposure to daylight on arrival at the new destination can also aid in resetting the internal clock.
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Insomnia—Melatonin has been studied in the treatment of various sleep disorders, including insomnia and delayed sleep-phase syndrome. It has been reported to improve sleep onset, duration, and quality when administered to healthy volunteers, suggesting a pharmacologic hypnotic effect. Melatonin has also been shown to increase rapid eye movement (REM) sleep. These observations have been applied to the development of ramelteon, a prescription hypnotic that is an agonist at melatonin receptors (see Chapter 22).
Clinical studies in patients with primary insomnia have shown that oral melatonin supplementation may alter sleep architecture. Melatonin appears effective in some patients who develop insomnia from β blockers. Subjective and objective improvements in sleep quality and improvements in sleep onset and sleep duration have been reported. Specifically, melatonin taken at the desired bedtime, with bedroom lights off, has been shown to improve morning alertness and quality of sleep as compared with placebo. These effects have been observed in both young and older adults (18–80 years of age). Interestingly, baseline endogenous melatonin levels were not predictive of exogenous melatonin efficacy.
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Preand postoperative anxiety in adults—Melatonin given as a premedication has been shown to reduce preoperative anxiety in adults. Melatonin may be as effective as midazolam in reducing anxiety before a surgical procedure (measured 50–100 minutes after administration). The effect of melatonin on postoperative anxiety in adults is mixed, but studies support an overall reduction in anxiety as compared to preoperative anxiety levels.
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Female reproductive function—The presence of melatonin within the female reproductive system appears widespread in mammals, and research suggests it plays a role in reducing oxidative stress. Melatonin receptors have been identified in ovarian granulosa cell membranes, and significant amounts of melatonin have been detected in follicular fluid. Some studies suggest it can be used as an adjunctive therapy in the treatment of infertility during in vitro fertilization by reducing oxidative stress and thereby improving the quality of oocytes and embryos during ovulation induction and egg retrieval. Melatonin requirements increase during pregnancy, and researchers are evaluating the role of melatonin in preeclampsia and neonatal neurologic morbidity. Importantly, melatonin has been shown to lack teratogenic effects when taken during pregnancy. Melatonin supplementation may decrease prolactin release in women and therefore should be used cautiously or not at all while nursing.
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