Melatonin Randomized Trial in Insomnia in the Elderly

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DESCRIPTION (provided by applicant): Chronic insomnia affects up to 35% of the elderly. It can significantly impair quality of life and daytime functioning. Currently, most medical therapy for insomnia involves sedative-hypnotic agents that may lead to dependence, withdrawal side effects and reduced efficacy after extended periods of use. A growing body of work has suggested that melatonin, a neurohormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, the primary circadian pacemaker, may play a role in mediating insomnia. Ongoing research at the University of Pennsylvania in 180 elderly insomnia patients has found statistically significant evidence of a decreased sleep efficiency in low melatonin insomniacs. Thus, melatonin production is impaired in a subgroup of elderly insomnia patients and this may contribute to their insomnia. However, melatonin treatment trials in elderly insomniacs have been equivocal. These studies have had serious methodologic limitations including inadequate sample size (Type II error), lack of objective measures of sleep or daytime functioning, and no placebo control arm. This has raised many questions such as whether melatonin deficiency is a marker of insomnia or, instead, a contributing factor and whether increased doses are needed to recreate the higher levels seen in the cerebrospinal fluid compartment. In addition, melatonin is widely used as an over-the-counter sleeping aid with litre true insight into its effectiveness/safety, especially in older adults. To address the primary hypothesis that melatonin can treat insomnia in melatonin-deficient elderly, the principal investigator proposes conducting a large randomized, double-blind clinical trial comparing low dose melatonin (0.4 mg), high dose melatonin (4.0 mg) and placebo in a well-defined group of elderly insomniacs with low melatonin levels (189 total subjects). The specific aims are to 1) evaluate the effectiveness of melatonin and 2) assess the daytime consequences and safety of melatonin treatment in this population. Intention-to-treat analysis will compare low dose melatonin, high dose melatonin, and placebo on objective and subjective parameters of sleep and daytime function. This protocol will extend well beyond the research done to date by rigorously testing the role of targeted melatonin replacement therapy as an effective treatment for insomnia in the elderly and by evaluating the safety profile of melatonin with a particular focus on daytime functioning.