Non-benzodiazepine hypnotic use for sleep disturbance in people aged over 55 years living with dementia: a series of cohort studies

Richardson, Kathryn, Savva, George, Boyd, Penelope, Aldus, Clare, Maidment, Ian, Pakpahan, Eduwin, Loke, Yoon, Arthur, Antony, Steel, Nicholas, Ballard, Clive, Howard, Robert and Fox, Chris (2021) Non-benzodiazepine hypnotic use for sleep disturbance in people aged over 55 years living with dementia: a series of cohort studies. Health Technology Assessment, 25 (1). ISSN 1366-5278

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Background: Sleep disturbance affects around 60% of people living with dementia (PLWD), and negatively impacts their quality of life and their carers. Hypnotic Z-drugs (zolpidem, zopiclone and zaleplon) are commonly used to treat insomnia, but their safety and efficacy has not been evaluated for PLWD. Objectives: To estimate the benefits and harms of Z-drugs in PLWD with sleep disturbance. Design: A series of observational cohort studies using existing data from (1) Primary care data linked to hospital admission data, and (2) Clinical cohort studies (CCS) of PLWD. Data sources: Primary care study: Clinical Practice Research Datalink linked to Hospital Episodes Statistics and Office of National Statistics mortality data. CCS: Resource Use and Disease Course in Dementia – Nursing Homes (REDIC), National Alzheimer’s Co-ordinating Center clinical dataset (NACC), and the Improving Well-being and Health for People with Dementia in nursing homes (WHELD) randomised controlled trial. Setting: Primary care study: 371 primary care practices in England; CCS: 47 nursing homes in Norway, 34 Alzheimer’s Disease Centers in the United States, and 69 care homes in England. Participants: Primary care study: NHS England primary care patients diagnosed with dementia aged over 55 years, and with sleep disturbance or prescribed Z-drugs or low-dose tricyclic antidepressants, followed over 2 years. CCS: PLWD consenting to participate followed over 3-years, 12-years, and 9-months, for REDIC, NACC and WHELD. Interventions: The primary exposure was prescription or use of Z-drugs. Secondary exposures included prescription or use of benzodiazepines, low-dose tricyclic antidepressants, and antipsychotics. Main outcome measures: Falls, fractures, infection, stroke, venous thromboembolism, mortality, cognitive function, and quality of life (QoL). There was insufficient data to investigate sleep disturbance. Results: The primary care and combined CCS studies included 6,809 and 18,659 PLWD, with 3,089 and 914 taking Z-drugs, respectively. New Z-drug use was associated with a greater risk of fractures [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01-1.94], with risk increasing with greater cumulative dose (p=0.002). The HR (95% CI) for Z-drug use and hip fracture was 1.59 (1.00-2.53) and for mortality was 1.34 (1.10-1.64). No excess risks of falls, infections, stroke, or venous thromboembolism were detected. Z-drug use also did not impact on cognition, neuropsychiatric symptoms, disability or QoL. Limitations: Primary care study: possible residual confounding due to difficulties identifying patients with sleep disturbance, and by dementia severity. CCS: the small numbers of PLWD taking Z-drugs and outcomes not necessarily being measured before Z-drug initiation restricted analyses. Conclusions: We observed a dose dependent increase in fracture risk, but no other harms, with Z-drug use in dementia. However, multiple outcomes were examined, increasing the risk of false positive findings. The mortality association was unlikely causal. Further research is needed to confirm the increased fracture risk. Decisions to prescribe Z-drugs may need to consider the risk of fractures, balanced against the impact of improved sleep for PLWD and their carers. Our findings suggest that when Z-drugs are prescribed, falls prevention strategies may be needed, and that the prescription should be regularly reviewed. Future work: More research is needed on safe and effective management strategies for sleep disturbance in PLWD. Study registration: EUPAS18006 Funding details: NIHR HTA 14/221/02

Item Type: Article
Additional Information: Early title: Non-benzodiazepine hypnotic (Z-drug) use for sleep disturbance in people living with dementia: a series of observational cohort studies
Uncontrolled Keywords: zopiclone,zaleplon,zolpidem,caregivers,sleep initiation and maintenance disorders,benzodiazepines,quality of life,accidental falls,venous thromboembolism,dementia,nursing homes,stroke,cognition,primary health care,hip fractures,cohort studies
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Medicine and Health Sciences > School of Health Sciences
Depositing User: LivePure Connector
Date Deposited: 09 Jan 2021 01:00
Last Modified: 20 Jan 2021 00:50
DOI: 10.3310/hta25010

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