A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease.
OBJECTIVE
To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer's disease.


METHODS
A multicenter, randomized, placebo-controlled clinical trial of 2 dose formulations of oral melatonin coordinated by the National Institute of Aging-funded Alzheimer's Disease Cooperative Study. Subjects with Alzheimer's disease and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin.


METHODS
Private homes and long-term care facilities.


METHODS
157 individuals were recruited by 36 Alzheimer's disease research centers. Subjects with a diagnosis of Alzheimer's disease were eligible if they averaged less than 7 hours of sleep per night (as documented by wrist actigraphy) and had 2 or more episodes per week of nighttime awakenings reported by the caregiver.


METHODS
Nocturnal total sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was defined by an automated algorithmic analysis of wrist actigraph data.


RESULTS
No statistically significant differences in objective sleep measures were seen between baseline and treatment periods for the any of the 3 groups. Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. Trends for a greater percentage of subjects having more than a 30-minute increase in nocturnal total sleep time in the 10-mg melatonin group and for a decline in the day-night sleep ratio in the 2.5-mg sustained-release melatonin group, compared to placebo, were also seen. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5-mg sustained-release melatonin group relative to placebo. There were no significant differences in the number or seriousness of adverse events between the placebo and melatonin groups.


CONCLUSIONS
Based on actigraphy as an objective measure of sleep time, melatonin is not an effective soporific agent in people with Alzheimer's disease.
Singer
Clifford
C
Department of Psychiatry, Oregon Health & Science University, Portland, USA. singerc@ohsu.edu
Tractenberg
Rochelle E
RE
Kaye
Jeffrey
J
Schafer
Kim
K
Gamst
Anthony
A
Grundman
Michael
M
Thomas
Ronald
R
Thal
Leon J
LJ
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications*; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000187:drug effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D017286:Polysomnography; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*
D000975:Antioxidants; D003692:Delayed-Action Preparations; D008550:Melatonin