Pharmacotherapies for Sleep Disturbances in Dementia

Summary

A Cochrane review [Abstract] 1 included 6 studies with a total of 326 subjects with Alzheimer's disease (AD). All trials included participants with night-time behaviours that are associated with disturbance or distress to caregivers. Melatonin, trazodone and ramelteon were studied. There was no RCTs of other drugs that are widely prescribed for sleep problems in AD. The melatonin and trazodone studies recruited people with moderate-to-severe AD; the ramelteon study was of people with mild-to-moderate AD. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. The treatment times varied from 2 to 10 weeks.

• Melatonin (4 trials, n=220): There was no evidence that melatonin, at doses up to 10 mg, improved any major sleep outcome over 8 to 10 weeks. The data was synthesised for two sleep outcomes (2 trials, n=184): total nocturnal sleep time (MD 10.68 minutes, 95% CI -16.22 to 37.59), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03). There was no difference between treatment and placebo groups for sleep efficiency, time awake after sleep onset or number of night-time awakenings, nor in cognition or performance of activities of daily living (ADLs). No serious adverse effects were reported.
• Trazodone (one trial, n=30): 50 mg at night for 2 weeks significantly 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), but there was no clear evidence of effect on 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). No effect was seen on daytime sleep, nor on cognition or ADLs. No serious adverse effects were reported.
• Ramelteon (one trial, n=68): results from a phase 2 trial at dose of 8 mg were available in summary form in a sponsor's synopsis. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or 8 weeks (end of treatment). The synopsis reported few significant differences from placebo for any sleep, behavioural or cognitive outcomes; none were likely to be of clinical significance. There were no serious adverse effects of ramelteon.

Comment: The quality of the evidence is downgraded by imprecise results (limited study size for each comparison) and indirectness of evidence (short follow-up time).