期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 76, 期 6, 页码 1010-1018出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glaa060
关键词
Polypharmacy; Drug Burden Index; Deprescribing; Frailty; Geriatric pharmacology
资金
- Penney Ageing Research Unit, Royal North Shore Hospital, Australia
- Ramsay Research and Teaching Fund, Royal North Shore Hospital, Australia
- National Institute on Aging, National Institutes of Health
- U.S. National Institute on Aging at the National Institutes of Health [R01 AG047891, P30AG021342, P30AG021342-16S1]
- NATIONAL INSTITUTE ON AGING [ZIAAG000361, ZIAAG000363] Funding Source: NIH RePORTER
The use of multiple medications and a high Drug Burden Index are linked with impaired physical function in older adults, but deprescribing may offer potential benefits. A preclinical study on mice found that chronic polypharmacy and a high DBI score can increase frailty and decrease function in old age, with drug withdrawal in old age able to reverse these outcomes. It was not the number of medications but the type and dose that caused adverse geriatric outcomes.
Polypharmacy (use of >= 5 medications) and increasing Drug Burden Index (DBI) score (measure of person's total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes.
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