People with dementia often have trouble sleeping, and this can severely harm patient and carer quality of life. Sleeping drugs called Z-drugs (which include zolpidem, zaleplon and zopiclone) are often used, but we don't know how safe they are or how well they work for people with dementia. Z-drugs might cause falls and fractures, worsen memory or making people more confused or agitated during the day. They might cause dehydration, stroke or infections by making people more sedated. We will use routinely collected information from the Clinical Practice Research Datalink to test whether these harmful events are more common in people with dementia who use Z-drugs compared to people with dementia who do not. We will study dementia patients who had a sleep disorder recorded by their GP, and will describe what medicines, if any, they were prescribed to improve their sleep. We will compare rates of harmful events in the two years after their sleep problem between those prescribed and not prescribed Z-drugs. Our research will help improve guidelines and advice for people with dementia who have difficulty with sleep, professionals who prescribe or review medication of dementia patients, and ultimately help patients and carers.
Objective: To estimate the unintended consequences of Z-drugs (zolpidem, zaleplon and zopiclone) when used for sleep disturbance in people with dementia (PwD). Methods Cohort study of UK patients diagnosed with dementia since the year 2000 with first evidence of sleep disturbance post dementia diagnosis. Evidence of sleep disturbance is defined as the first of a diagnosis/symptom code for sleep disturbances or for a prescription of a Z-drug, low dose tricyclic antidepressant (LDTCA) or melatonin (index date). We will follow patients for the following outcomes: falls, fractures, infections, stroke, venous thromboembolism, mortality, agitation/psychosis, new medication use, and healthcare utilisation. Sleep medication classes considered as exposures include Z-drugs, benzodiazepines, melatonin, and LDTCA. Statistical analysis Hazard ratios associated with any prescription from each sleep medication class compared to no sleep prescription for each binary outcome shall be estimated using Cox regression models adjusted for a range of potential confounders. Negative binomial regression will be used to calculate incidence rate ratios for the number of GP visits and hospital visits in the two years post index date. Sleep medication exposure will be modelled as time-varying, such that PwD at the index date will be included for analysis in the 'no treatment' group until initiation of their first treatment.
Specific outcomes: 1. Incident (a) fracture (any location) (b) hip fracture (c) forearm fracture. Hip fracture recording in CPRD has been well validated (PPV of 91%). 2. Incident fall. GP records of falls may under-represent all falls that occur in the older population, but more accurately represent 'injurious falls requiring medical attention'. 3. Mortality (based on CPRD GOLD's death dates). 4. Incident (a) infection (any), (b) urinary tract infection or respiratory infections, (c) antibiotic use. Respiratory tract infection has been validated in CPRD (PPV of 97%). 5. Stroke. Stroke has been well validated in CPRD. 6. Venous thromboembolism. Diagnosis in CPRD has been validated (PPV of 94%). 7. Incident agitation/psychosis. Psychosis diagnosis has been validated in CPRD (PPV of 93%), but the symptoms may be under-reported. 8. Additional medication use: (a) sedatives and other sleep medications (ATC N05C or N05BA), (b) antipsychotics (ATC N05A), (c) antidepressants (ATC N06A) 9. Health care utilisation: number of GP visits; hospital admissions..
Kathryn Richardson - Chief Investigator - University of East Anglia
Kathryn Richardson - Corresponding Applicant - University of East Anglia
Antony Arthur - Collaborator - University of East Anglia
Chris Fox - Collaborator - University of East Anglia
Clare Aldus - Collaborator - University of East Anglia
clive Ballard - Collaborator - University of Exeter
George Savva - Collaborator - University of East Anglia
Ian Maidment - Collaborator - Aston University, Birmingham
Nicholas Steel - Collaborator - University of East Anglia
Penelope Boyd - Collaborator - University of East Anglia
Robert Howard - Collaborator - UCL Hospital
Yoon Loke - Collaborator - University of East Anglia
HES Admitted Patient Care;HES Admitted Patient Care;ONS Death Registration Data;ONS Death Registration Data;Practice Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation