Melatonin and Its Agonist Ramelteon in Alzheimer's Disease: Possible Therapeutic Value
Table 1
Clinical studies on melatonin efficacy in AD.
Design
Subjects
Treatment
Study’s duration
Measured
Results
Reference
Open-label study
10 (6, 4) demented patients
3 mg melatonin p.o./daily at bed time
3 weeks
Daily logs of sleep and wake quality completed by caretakers
Seven out of ten dementia patients having sleep disorders treated with melatonin showed a significant decrease in sundowning and reduced variability of sleep onset time
Daily logs of sleep and wake quality completed by caretakers. Neuropsychological assessment.
At the time of assessment, a significant improvement of sleep quality was found. Sundowning was not longer detectable in 12 patients and persisted, although attenuated in 2 patients. Clinically, the patients exhibited lack of progression of the cognitive and behavioral signs of the disease during the time they received melatonin.
Daily logs of sleep and wake quality completed by caretakers. Neuropsychological assessment.
Melatonin improved sleep and suppressed sundowning, an effect seen regardless of the concomitant medication employed to treat cognitive or behavioral signs of AD.
2.5 mg slow-release melatonin, or 10 mg melatonin or placebo at bed time
2 months
Actigraphy. Caregiver ratings of sleep quality
Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5 mg sustained-release melatonin group relative to placebo.
Morning light exposure (2,500 lux, 1 h) and 5 mg melatonin () or placebo () in the evening. Control subjects () received usual indoor light (150–200 lux).
10 weeks
Night time sleep variables, day sleep time, day activity, day : night sleep ratio, and rest-activity parameters were determined using actigraphy.
Light treatment alone did not improve night time sleep, daytime wake, or rest-activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest-activity rhythm.