Melatonin and Its Agonist Ramelteon in Alzheimer's Disease: Possible Therapeutic Value
Table 2
Clinical studies on melatonin efficacy in MCI.
Design
Subjects
Treatment
Study’s duration
Measured
Results
Reference(s)
Double-blind, placebo-controlled, crossover study
10 (4, 6) patients with mild cognitive impairment (MCI)
6 mg melatonin p.o./daily at bed time
10 days
Actigraphy. Neuropsychological assessment.
Enhanced the rest-activity rhythm and improved sleep quality (reduced sleep onset latency and in the number of transitions from sleep to wakefulness Total sleep time unaffected. The ability to remember previously learned items improved along with a significant reduction in depressed mood.
Sleep questionnaire and a battery of cognitive tests at baseline and at 4 weeks
Melatonin administration improved reported morning “restedness” and sleep latency after nocturnal awakening and also improved scores on the California Verbal Learning Test-interference subtest.
25 had received daily 3–9 mg of a fast-release melatonin preparation p.o. at bedtime. Melatonin was given in addition to the standard medication
9–18 months
Daily logs of sleep and wake quality. Initial and final neuropsychological assessment.
Patients treated with melatonin showed significantly better performance in neuropsychological assessment. Abnormally high. Beck Depression Inventory scores decreased in melatonin-treated patients, concomitantly with an improvement in wakefulness and sleep quality.
Randomized, double blind, placebo-controlled study
354 individuals with age-related cognitive decay
prolonged release melatonin (Circadin, 2 mg) or placebo, 2 h before bedtime
3 weeks
Leeds Sleep Evaluation and Pittsburgh Sleep Questionnaires, Clinical Global Improvement scale score and quality of life.
PR-melatonin resulted in significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency, and quality of life
Long-term, double-blind, placebo-controlled, factorial randomized study
189 (19, 170) individuals with age-related cognitive decay
Long-term daily treatment with whole-day bright (1000 lux) or dim (300 lux) light. Evening melatonin (2.5 mg) or placebo administration
1 to 3.5 years
Standardized scales for cognitive and noncognitive symptoms, limitations of activities of daily living, and adverse effects assessed every 6 months.
Light attenuated cognitive deterioration and also ameliorated depressive symptoms. Melatonin shortened sleep onset latency and increased sleep duration but adversely affected scores for depression. The combined treatment of bright light plus melatonin showed the best effects.
Prospective, randomized, double-blind, placebo-controlled, study
22 (15, 7) individuals with age-related cognitive decay
Participants received 2 months of melatonin (5 mg o.o./day) and 2 months of placebo
2 months
Sleep disorders were evaluated with the Northside Hospital Sleep Medicine Institute (NHSMI) test. Behavioral disorders were evaluated with the Yesavage Geriatric Depression Scale and Goldberg Anxiety Scale.
Melatonin treatment significantly improved sleep quality scores. Depression also improved significantly after melatonin administration.