Name:	Melatonin
FDA Phase:	Not FDA regulated
Primary Medical Role:	Over-the-counter treatment for insomnia.
Role in Alzheimer's Disease:	A number of studies have documented disturbances in circadian rhythm associated with Alzheimer's disease, resulting in changes of body temperature, hormonal concentrations, sleep and wakefulness patterns, and rest- activity cycles. These cycles are regulated by the daily rise and fall of melatonin levels, and as one of the symptoms associated with the aging process has been a decline in the amplitude of the melatonin rhythm, there is currently interest in using melatonin to treat circadian disturbances in Alzheimer's disease. In both in vivo and in vitro experiments melatonin has been shown to reduce lipid peroxidation and oxidative damage to nuclear DNA. A variety of studies also suggest melatonin may inhibit Abeta toxicity. Some researchers hypothesize that an age- related decline in melatonin could be a cause of Alzheimer's, but it is just as probable that the disruption of the melatonin cycle is the result of an underlying disease process.
Pharmacological Role:	Melatonin is a natural hormone secreted by the pineal gland. It plays an important role in regulating the circadian sleep-wake cycle, but has also been reported in the popular media as being a 'miracle drug' with putative wide-ranging effects on health, largely unsupported by scientific studies.
Contraindications:	Almost nothing is known about interactions between melatonin and other drugs and diseases, but because melatonin is a potent natural hormone, caution should be used regarding the timing, dosage, etc. Probably best avoided by children, pregnant women and nursing mothers.
Side Effects:	Tolerance, fatigue, nightmares, hypotension, sleep disorders, abdominal pain,and other side effects have been reported. Repeated administration of a pharmacologic dose (3mg) may disrupt, rather than improve, sleep in some individuals. Some authorities say melatonin use on consecutive nights should be avoided and only the lowest effective hypnotic dose should be taken. More research needs to be done on potential effects on reproductive hormones, deleterious metabolites, effects on the central nervous system, the cardiovascular system and platelet aggregation, glucose metabolism, immunology, and cancer.
Evidence pro its efficacy:	Efficacy in treating circadian disturbances in Alzheimer's patients has been reported in individual cases, but needs to be verified in large-scale clinical trials.
Evidence con its efficacy:	Anecdotal reports of people who do not respond to melatonin. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease published in November 2003 found no significant improvement in objective measures of sleep in AD patients. See ARF News story.
Dosage:	The 'pharmacologic dose' is 3 mg, but some research indicates lower doses (0.3 mg) are effective and 3 mg may result in disrupted sleep. The pharmacologically effective dose has not been established by rigorous studies.
Notes:	In the U.S. melatonin is currently classified as a dietary supplement and not subject to FDA approval. In Europe, melatonin is classified as a neurohormone and cannot be sold over the counter. There is very little data on the toxicology of melatonin. The Alzheimer's Disease Cooperative Study is seeking people with diagnosed Alzheimer's disease to participate in a clinical trial to study the efficacy of melatonin as a treatment for sleep disturbances in AD.

References

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