A Cochrane systematic review has found a clear lack of evidence in the pharmacologic guidance of sleep problems in dementia.
Patients with dementia experience sleep problems, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness. These disturbances are associated with significant distress to caregivers, higher healthcare costs, and institutionalism.
To evaluate the effects of any drug treatment vs. placebo for sleep disorders in patients with dementia, researchers identified all relevant randomized controlled trials. They included trials that compared a drug to placebo and that had the primary objective of improving sleep in patients with dementia who had an identified sleep disturbance at baseline.
Six trials evaluating 3 drugs—melatonin (n=222), trazodone (n=30), and ramelteon (n=74)—were eligible for inclusion.
Patients in the trazodone study and almost all in the melatonin studies exhibited moderate-to-severe dementia due to Alzheimer’s disease. Patients in the ramelteon study had mild-to-moderate Alzheimer’s disease. Primary sleep outcomes were measured using actigraphy.
Overall, study authors found no evidence that melatonin (up to 10mg) improved any major sleep outcome over 8–10 weeks in patients with Alzheimer’s who were identified as having a sleep disturbance. For total nocturnal sleep time, mean difference (MD) was 10.68 minutes (95% CI: -16.22 to 37.59) and the ratio of daytime sleep to nighttime sleep had a mean difference -0.13 (95 %CI: -0.29 to 0.03).
No difference was seen for sleep efficiency, time awake after sleep onset, or number of nighttime awakenings between the melatonin and placebo groups from single studies. Base on two studies, melatonin was not fond to effect cognition or performance of activities of daily living.
For trazodone, there was low-quality evidence that 50mg taken at night for 2 weeks improved total nocturnal sleep time (MD 42.46 minutes, 95% CI: 0.9 to 84.0) and sleep efficiency (MD 8.53%, 95% CI: 1.9 to 15.1) in patients with moderate-to-severe Alzheimer’s disease. However it did not affect the amount of time spent awake after sleep onset (MD -20.41, 95% CI: -60.4 to 19.6) or the number of nocturnal awakenings (MD -3.71, 95% CI: -8.2 to 0.8). In addition, trazodone had no effect on daytime sleep, cognition or activities of daily living.
For ramelteon, data from a Phase 2 trial evaluating the 8mg dose taken at night was considered to be of low quality. Authors found no effect of ramelteon on total nocturnal sleep time at 1 week or 8 weeks in patients with mild-to-moderate Alzheimer’s disease. A few significant differences between ramelteon and placebo were reported regarding sleep, behavioral, or cognitive outcomes; none of which were likely to be clinically significant.
Authors concluded that “high pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in dementia” are needed, and that “systematic assessment of adverse effects is essential.”
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