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Pharmacotherapies for sleep disturbances in dementia

Overview of attention for article published in Cochrane database of systematic reviews, November 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Mentioned by

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1 news outlet
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125 tweeters
facebook
2 Facebook pages
wikipedia
2 Wikipedia pages

Citations

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42 Dimensions

Readers on

mendeley
222 Mendeley
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Title
Pharmacotherapies for sleep disturbances in dementia
Published in
Cochrane database of systematic reviews, November 2016
DOI 10.1002/14651858.cd009178.pub3
Pubmed ID
Authors

Jenny McCleery, Daniel A. Cohen, Ann L Sharpley

Abstract

Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant caregiver distress, increased healthcare costs, and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population. To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia, through identification and analysis of all relevant randomised controlled trials (RCTs). We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, in March 2013 and again in March 2016, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, sundowning. We included RCTs that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline. Trials could also include non-pharmacological interventions, as long as both drug and placebo groups had the same exposure to them. Two review authors independently extracted data on study design, risk of bias, and results from the included study reports. We obtained additional information from study authors where necessary. We used the mean difference as the measure of treatment effect, and where possible, synthesized results using a fixed-effect model. We found six RCTs eligible for inclusion for three drugs: melatonin (222 participants, four studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), trazodone (30 participants, one study), and ramelteon (74 participants, one study, no peer-reviewed publication, limited information available).The participants in the trazodone study and almost all participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. Only two studies made a systematic assessment of adverse effects. Overall, the evidence was at low risk of bias, although there were areas of incomplete reporting, some problems with participant attrition, related largely to poor tolerance of actigraphy and technical difficulties, and a high risk of selective reporting in one trial that contributed very few participants. The risk of bias in the ramelteon study was unclear due to incomplete reporting.We found no evidence that melatonin, at doses up to 10 mg, improved any major sleep outcome over 8 to 10 weeks in patients with AD who were identified as having a sleep disturbance. We were able to synthesize data for two of our primary sleep outcomes: total nocturnal sleep time (mean difference (MD) 10.68 minutes, 95% CI -16.22 to 37.59; N = 184; two studies), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; N = 184; two studies). From single studies, we found no difference between melatonin and placebo groups for sleep efficiency, time awake after sleep onset, or number of night-time awakenings. From two studies, we found no effect of melatonin on cognition or performance of activities of daily living (ADL). No serious adverse effects of melatonin were reported in the included studies. We considered this evidence to be of low quality.There was low-quality evidence that trazodone 50 mg given at night for two weeks improved total nocturnal sleep time (MD 42.46 minutes, 95% CI 0.9 to 84.0; N = 30; one study), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; N = 30; one study) in patients with moderate-to-severe AD, but it did not affect the amount of time spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6; N = 30; one study), or the number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8; N = 30; one study). No effect was seen on daytime sleep, cognition, or ADL. No serious adverse effects of trazodone were reported.Results from a phase 2 trial investigating ramelteon 8 mg administered at night were available in summary form in a sponsor's synopsis. Because the data were from a single, small study and reporting was incomplete, we considered this evidence to be of low quality in general terms. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or eight weeks (end of treatment) in patients with mild-to-moderate AD. 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 from ramelteon. We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in dementia. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in dementia, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin (up to 10mg) helped sleep problems in patients with moderate to severe dementia due to AD. There was some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in dementia. Systematic assessment of adverse effects is essential.

Twitter Demographics

The data shown below were collected from the profiles of 125 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 222 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Unknown 221 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 36 16%
Student > Bachelor 31 14%
Researcher 25 11%
Student > Ph. D. Student 21 9%
Student > Postgraduate 17 8%
Other 54 24%
Unknown 38 17%
Readers by discipline Count As %
Medicine and Dentistry 72 32%
Nursing and Health Professions 24 11%
Psychology 21 9%
Neuroscience 17 8%
Pharmacology, Toxicology and Pharmaceutical Science 11 5%
Other 29 13%
Unknown 48 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 86. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 January 2020.
All research outputs
#222,321
of 14,575,084 outputs
Outputs from Cochrane database of systematic reviews
#506
of 11,003 outputs
Outputs of similar age
#7,444
of 237,069 outputs
Outputs of similar age from Cochrane database of systematic reviews
#10
of 156 outputs
Altmetric has tracked 14,575,084 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,003 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.3. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 237,069 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 156 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.