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Cited by 407Circadian rhythm and melatoninSleep and related disordersDementia and Cognitive Impairment Research

A Multicenter, Placebo-controlled Trial of Melatonin for Sleep Disturbance in Alzheimer's Disease

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Singer, Clifford, Tractenberg, Rochelle E., Kaye, Jeffrey, Schafer, Kim, Gamst, Anthony, Grundman, Michael, Thomas, Ronald, Thal, Leon J.·2003·Sleep
DOI 10.1093/sleep/26.7.893PMC PMC4418658
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Abstract

OBJECTIVES: To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer's disease. DESIGN: 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. SETTING: Private homes and long-term care facilities. PARTICIPANTS: 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. MEASUREMENTS: 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.

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  • A double-blind, multicentre study in 157 individuals with AD showed that evening melatonin treatment improved cognition, decreased nocturnal activity and increased sleep.

    “a double-blind, multicentre study in 157 individuals with AD showed that evening melatonin treatment improved cognition, decreased nocturnal activity and increased sleep302”

    From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [302]

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Research works printed but not linked: 5

  1. Sack RL. Melatonin. Sci Med 1998;5:5:8-17.
  2. Singer C, Wild, Sack R, Lewy A. High dose melatonin is well tolerated by the elderly. Sleep Res 1994c;23:86.
  3. Singer C, Moffit M, Colling E, et al. Low dose melatonin administration and nocturnal activity levels in patients with Alzheimer's disease. Sleep Res 1997;26:752.
  4. Sack RL, Stevenson J, Lewy AJ. Entrainment of a previously free-running blind human with melatonin. Sleep Res 1990;19:404.
  5. Colling E, Wright M, Lahr S, Schmedlen L, DeJongh L, Singer C. A comparison of wrist actigraphy with polysomnography as an instrument of sleep detection in elderly persons. Sleep 2000;23:A378.

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Authors
Singer, C., Tractenberg, R. E., Kaye, J., Schafer, K., Gamst, A., Grundman, M., Thomas, R., & Thal, L. J.
Affiliations
  • Oregon Health & Science University (US)
  • Georgetown University (US)
  • University of California San Diego (US)
Corresponding author
Singer, Clifford
ORCID
Venue
Sleep
Publisher
Oxford University Press (OUP)
Published
2003-10
Volume
26
Issue
7
Pages
893-901
ISSN
  • 0161-8105 (ISSN-L)
  • 1550-9109
DOI
10.1093/sleep/26.7.893
PMC
PMC4418658
OpenAlex
W1649820184
Cited by
407
References
62
Citations by year
2026: 10 · 2025: 15 · 2024: 15 · 2023: 14 · 2022: 13 · 2021: 15 · 2020: 16 · 2019: 11 · 2018: 14 · 2017: 9 · 2016: 24 · 2015: 20 · 2014: 25 · 2013: 20 · 2012: 19
FWCI
7.03
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • SLEEP (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (AG 10483, U01AG010483, U19AG010483)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
melatonin, Alzheimer's disease, insomnia, dose comparison, actigraphy, total sleep time, wake after sleep onset, sleep efficiency, long-term care, adverse events
MeSH terms
Aged, Alzheimer Disease, Antioxidants, Circadian Rhythm, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Male, Melatonin, Severity of Illness Index, Sleep Wake Disorders, Polysomnography

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