Almost half the patients with Alzheimer's disease experience some sleep disruption, ranging from nighttime awakenings to a complete reversal of the diurnal sleep/wake cycle. Whatever memory and other cognitive loss is already present in these patients is likely worsened by the loss of normal sleep. Sleep disruption is also a major factor in decisions by family members to move a patient into a nursing home.

Melatonin has shown some benefit anecdotally and in pilot studies, but because it is not a drug that can be patented, there has been no rush to submit the compound to clinical trials. The Alzheimer's Disease Cooperative Study, funded by the National Institute on Aging to conduct such trials, has now addressed this research gap.

Led by Clifford Singer of Oregon Health and Science University in Portland, the trial lasted two months and was conducted at 36 different clinics. Two sustained release doses of melatonin—one termed "moderately high" by the authors (10 mg) and the other "moderately low" (2.5 mg)—were compared to placebo in 157 AD patients with sleep disruption.

The authors unfortunately found no significant improvement in objective measures of sleep (sleep maintenance, sleep duration, or day-night sleep ratio). They do not rule out experimenting with melatonin in individual AD patients, however, citing nonsignificant trends toward improvement in several measures, as well as their own evidence that the drug "is very well-tolerated, even at a high dose." They also note that one of their patients showed dramatic improvement, and he may have suffered from a circadian rhythm disturbance unrelated to his Alzheimer's pathology.

“Nevertheless, the essentially negative results of this trial leave us without any proven therapy for most AD patients with insomnia, and clinicians are left to make intuitive choices of sleep therapies until more conclusive data are available," conclude the authors.—Hakon Heimer.

Reference:
Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep. 2003 Nov 1;26(7):893-901. Abstract