A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease

Clifford Singer, Rochelle E. Tractenberg, Jeffrey Kaye, Kim Schafer, Anthony Gamst, Michael Grundman, Ronald Thomas, Leon J. Thal

Research output: Contribution to journalArticle

277 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalSleep
Volume26
Issue number7
StatePublished - Nov 1 2003

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Melatonin
Alzheimer Disease
Sleep
Placebos
Actigraphy
Wrist
Caregivers
Sleep Initiation and Maintenance Disorders
Long-Term Care
Therapeutics
Quality Improvement
Randomized Controlled Trials

ASJC Scopus subject areas

  • Physiology

Cite this

Singer, C., Tractenberg, R. E., Kaye, J., Schafer, K., Gamst, A., Grundman, M., ... Thal, L. J. (2003). A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep, 26(7), 893-901.

A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. / Singer, Clifford; Tractenberg, Rochelle E.; Kaye, Jeffrey; Schafer, Kim; Gamst, Anthony; Grundman, Michael; Thomas, Ronald; Thal, Leon J.

In: Sleep, Vol. 26, No. 7, 01.11.2003, p. 893-901.

Research output: Contribution to journalArticle

Singer, C, Tractenberg, RE, Kaye, J, Schafer, K, Gamst, A, Grundman, M, Thomas, R & Thal, LJ 2003, 'A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease', Sleep, vol. 26, no. 7, pp. 893-901.
Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M et al. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep. 2003 Nov 1;26(7):893-901.
Singer, Clifford ; Tractenberg, Rochelle E. ; Kaye, Jeffrey ; Schafer, Kim ; Gamst, Anthony ; Grundman, Michael ; Thomas, Ronald ; Thal, Leon J. / A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. In: Sleep. 2003 ; Vol. 26, No. 7. pp. 893-901.
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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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