Melatonin deficiency and its implications for the treatment of insomnia in elderly subjects

Purpose: Melatonin, the major hormone produced nocturnally by the pineal gland, is involved in the regulation of sleep in humans. Melatonin production decreases with advancing age and is impaired in several clinical syndromes and by certain drugs. Here we review the data on the link between melatonin deficiency and sleep, and the efficacy of melatonin replacement in age-related insomnia. Methods: Studies and review articles that reported on the correlation of endogenous melatonin and sleep and effects of exogenous melatonin on sleep were selected from the Medline database and from major conferences on sleep and chronobiology. Results: Low or distorted melatonin rhythms have repeatedly been reported in middle-aged and elderly insomniacs. In elderly insomniacs, melatonin replacement therapy was found to decrease significantly sleep latency and, in some studies, to increase sleep efficiency and decrease wake time after sleep onset. In addition, melatonin decreased sleep latency and increased sleep efficiency and mean total sleep time in chronic benzodiazepine-using elderly patients. In these studies, sleep was assessed objectively by means of wrist actigraphy or polysomnography. Conclusion: These data show an association between melatonin rhythm disturbances and psychophysiological insomnia. Melatonin replacement therapy may thus provide a rational approach to treat age-related insomnia in the elderly.