Pharmacology management of major neurocognitive disorders in the United Kingdom: a population-based drug utilization study

Background: Major neurocognitive disorders (MNCD) affect 1 in 11 persons over age 65. Cholinesterase inhibitors (ChEIs, i.e. donepezil, galantamine, and rivastigmine) and memantine are the only approved drugs for the management of MNCD in both the United Kingdom (UK) and Canada. The objective of this thesis was to describe the sex, age, and clinical characteristics associated with MNCD drug utilization, and to examine how prescription patterns vary with these characteristics.Methods: I assembled a retrospective, population-based inception cohort of all patients aged 65+ years with a new diagnosis of MNCD between 1997 and 2017 in the Clinical Practice Research Datalink, a primary care database with 15 million patient records from over 700 primary care practices in the UK. Patients were followed from MNCD diagnosis until the date of departure from the general practitioner practice, death, or March 2017. MNCD drug utilization patterns included time from date of diagnosis to medication initiation, switches, adherence and persistence, which were described overall, by sex, age group (65-74, 75-84, 85-94, 95+) and MNCD subtype (Alzheimer's, vascular, mixed, other [dementia with Lewy bodies, frontotemporal and Parkinson's] and non-specific). Associations between patient characteristics and drug initiation, switches, discontinuation and non-adherence were compared using Cox proportional hazards regression models, presented as hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant demographic and clinical covariates.Results: A total of 91,025 patients with MNCD were identified, among whom 25,071 (28%) received at least 1 MNCD drug prescription during follow-up and 13% of initiators switched to a second MNCD drug. Persistence was low (82% after the first trial, 56% after 6 months, 19% after 2 years), and adherence was modest among those who were persistent (53% at 2 years). Compared to male patients, female patients were more likely to initiate treatment with donepezil (adjusted HR=1.10, 95% CI 1.07-1.14), less likely to discontinue treatment with donepezil (adjusted HR=0.96, 95% CI 0.93-0.99) and less likely to become non-adherent (adjusted HR=0.91, 95% CI 0.87-0.96) to donepezil treatment. As compared to patients diagnosed at age 65-74, those diagnosed over age 95 were more frequently prescribed memantine (28%, versus 9%), less likely to switch medications (adjusted HR=0.25, 95% CI 0.23-0.28), were less persistent and had a higher rate of non-adherence. There were observed differences among the 5 dementia subtypes with respect to MNCD treatment initiation, switches and persistence but not adherence. Conclusion: In this population-based inception cohort, the largest MNCD primary care drug utilization study conducted to date, MNCD drug utilization varied by sex, age and MNCD subtype.

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