Researchers Find Multiple Medications Cause Frailty, but Effects Can Be Reversed

A world-first study by a team from the Kolling Institute of Medical Research in Australia may inform the future use of multiple medications by older people, minimizing adverse impacts such as frailty.

The longitudinal research, published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, is the first preclinical study to demonstrate that chronic polypharmacy increases frailty and impairs function in old age, and that stopping some medications is an effective way to reduce these harms.

Research lead Sarah Hilmer, BScMed (Hons), MBBS (Hons), FRACP, PhD, said there is a large body of observational evidence associating multiple medications with adverse geriatric outcomes such as falls and confusion.

“There has however, been a lack of data identifying whether multiple medications actually cause these adverse geriatric outcomes or are just an indicator of disease,” said Hilmer, head of the Department of Clinical Pharmacology at Royal North Shore Hospital, and University of Sydney Conjoint Professor of Geriatric Pharmacology.

“There has been uncertainty about whether it is the number of drugs, the type or the dose of drugs that drive these outcomes, and whether these effects are reversible once the medications are stopped.

“Our research, conducted by Dr. John Mach with a team of local, national, and international scientists, applied rigorous methods in ageing biology and biostatistics to measure the impact of multiple medications in old age and evaluate whether they actually cause adverse geriatric outcomes.

“For the first time, we found that multiple medications increased frailty and impaired function in old age, and interestingly, it was not the number of drugs, but the type and dose of medications that caused the adverse outcomes.

“Importantly, we also found that the adverse effects on frailty and function reduced after stopping the medications.

“This research provides the critical evidence required to inform a medication review in our ageing population, not just in Australia, but also internationally.

“We now know which mix of medications cause frailty and reduce independence in old age, and that these effects are reversible once the medications are stopped.

“Even if an older person has taken medications for many years, if the risk starts to outweigh the benefits, we can improve their function by withdrawing unnecessary drugs.

“As a geriatrician, this gives me the evidence I need to optimize medications for my older patients. I can be confident about which drug exposures are exacerbating frailty, and weigh those risks against any potential benefits.

“It also means that I know their function and independence is likely to improve by withdrawing medications.

“We expect our model will have wide ranging applications to help assess other interventions to improve health in old age, such as a new therapeutic drug or vaccine,” Hilmer said.

Collaborators from a large number of organizations were involved in the research, including the Kolling Institute of Medical Research, Royal North Shore Hospital, the University of Sydney, Ageing and Alzheimers Institute, Centre for Education and Research on Ageing, and ANZAC Research Institute in Australia; Yale University, Harvard Medical School and the National Institute on Aging in the U.S.; and Dalhousie University in Canada. The journal article is titled “Chronic polypharmacy with increasing Drug Burden Index (DBI) exacerbates frailty and impairs physical function, with effects attenuated by deprescribing, in aged mice.”

This latest research supports earlier work by Hilmer’s team to develop a clinical risk assessment tool to guide a medication review in older patients. The Drug Burden Index measures a patient’s cumulative exposure to medications that impair function and increase frailty. This tool is being adopted throughout hospitals, community and residential aged care settings in Australia and internationally.

###

The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences is a peer-reviewed publication of The Gerontological Society of America (GSA), the nation's oldest and largest interdisciplinary organization devoted to research, education, and practice in the field of aging. The principal mission of the Society — and its 5,500+ members — is to advance the study of aging and disseminate information among scientists, decision makers, and the general public. GSA’s structure also includes a policy institute, the National Academy on an Aging Society, and an educational unit, the Academy for Gerontology in Higher Education.