Higher Dose 'Z-Drugs' Tied to Serious Risks in Dementia Pati
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Sleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia.

Researchers used data from 27,090 patients diagnosed with dementia from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. They compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines.

They defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to more than 7.5 mg zopiclone or more than 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates.

Results
-- The mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women.

-- Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67, 1.96, 1.33 and 1.88 respectively.

-- They observed similar associations when compared to non-sedative-users with proximal GP consultation.

-- Minimal or inconsistent excess risks were observed at less than 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism.

-- They observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR of 0.73).

Conclusively, higher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed.

Source: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01821-5
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