Table 1.
Studies including treatment of Alzheimer’s disease (AD) patients with melatonin.
| Design | Subjects | Treatment | Time | Measured | Results | Reference |
|---|---|---|---|---|---|---|
| Open-label study | 10 AD patients | 3 mg melatonin p.o./daily at bed time | 3 weeks | Daily logs of sleep and wake quality completed by caretakers | 7 out of 10 dementia patients having sleep disorders treated with melatonin showed a significant decrease in sundowning and reduced variability of sleep onset time | [155] |
| Open-label study | 14 AD patients | 9 mg melatonin p.o./daily at bed time | 22 to 35 months | Daily logs of sleep and wake quality completed by caretakers. Neuro-psychological assessment | Sundowning was no longer detectable in 12 patients and persisted, although attenuated in 2 patients. A significant improvement of sleep quality was found. Lack of progression of the cognitive and behavioral signs of the disease during the time they received melatonin | [156] |
| Case report | Mono-zygotic twins with AD of 8 years duration | One of the patients was treated with melatonin 9 mg p.o./daily at bed time. | 36 months | Neuro-psychological assessment. Neuroimaging | Sleep and cognitive function severely impaired in the twin not receiving melatonin as compared to the melatonin-treated twin | [157] |
| Open-label study | 11 AD patients | 3 mg melatonin p.o./daily at bed time | 3 weeks | Daily logs of sleep and wake quality | Significant decrease in agitated behaviors in all three shifts; significant decrease in daytime sleepiness | [158] |
| Open-label, placebo-controlled trial | 14 AD patients | 6 mg melatonin p.o./daily at bed time or placebo | 4 weeks | Daily logs of sleep and wake quality completed by caretakers. Actigraphy | AD patients receiving melatonin showed a significantly reduced percentage of nighttime activity compared to a placebo group | [159] |
| Randomized double blind placebo-controlled cross over study | 25 AD patients | 6 mg of slow release melatonin p.o. or placebo at bed time | 7 weeks | Actigraphy | Melatonin had no effect on median total time asleep, number of awakenings or sleep efficiency | [160] |
| Open-label study | 45 AD patients | 6–9 mg melatonin p.o./daily at bed time | 4 months | Daily logs of sleep and wake quality completed by caretakers. Neuro-psychological assessment | Melatonin improved sleep and suppressed sundowning, an effect seen regardless of the concomitant medication employed | [161] |
| Randomized placebo-controlled clinical trial | 157 AD patients | 2.5-mg slow-release melatonin, or 10-mg melatonin or placebo at bed time | 2 months | Actigraphy. Caregiver ratings of sleep quality | Non significant trends for increased nocturnal total sleep time and decreased wake after sleep onset in the melatonin groups. Caregiver ratings of sleep quality showed a significant improvement in the 2.5-mg sustained-release melatonin group relative to placebo | [162] |
| Double-blind, placebo-controlled study | 20 AD patients | Placebo or 3 mg melatonin p.o./daily at bed time | 4 weeks | Actigraphy. Neuro-psychological assessment | Melatonin significantly prolonged the sleep time and decreased activity in the night. Cognitive function was improved by melatonin | [163] |
| Open-label study | 7 AD patients | 3 mg melatonin p.o./daily at bed time | 3 weeks | Actigraphy. Neuro-psychological assessment. | Complete remission of day-night rhythm disturbances or sundowning was seen in 4 patients, with partial remission in other 2 | [164] |
| Randomized placebo-controlled study | 17 AD patients | 3 mg melatonin p.o./daily at bed time (7 patients). Placebo (10 patients) | 2 weeks | Actigraphy. Neuro-psychological assessment. | In melatonin-treated group, actigraphic nocturnal activity and agitation showed significant reductions compared to baseline | [165] |
| Case report | 68-year-old man with AD who developed rapid eye movement (REM) sleep behavior disorder | 5–10 mg melatonin p.o./daily at bed time. | 20 months | Polysomno-graphy | Melatonin was effective to suppress REM sleep behavior disorder | [166] |
| Randomized placebo-controlled study | 50 AD patients | Morning light exposure (2500 lux, 1 h) and 5 mg melatonin (N = 16) or placebo (N = 17) in the evening | 10 weeks | Actigraphy | Light treatment alone did not improve nighttime sleep, daytime wake, or rest-activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest-activity rhythm | [167] |
| Randomized placebo-controlled study | 41 AD patients | Melatonin (8.5 mg immediate release and 1.5 mg sustained release) (N = 24) or placebo (N = 17) administered at 22:00 h | 10 days | Actigraphy | There were no significant effects of melatonin, compared with placebo, on sleep, circadian rhythms, or agitation | [168] |
p.o.: per os.