Potential Contribution of Medications to Frailty

To the Editor: With interest we read the article by Sanders and colleagues on the understanding of the physiological basis of frailty. Disease burden, defined using the Physiologic Index of Comorbidity, was significantly associated with frailty, independent of inflammation, coagulation, and diagnosed medical conditions. Although this important study demonstrates the contribution of physiological changes to frailty, individuals’ medicines may have confounded the cause–effect relationship. Polypharmacy, use of five or more medications, is common in older adults with chronic diseases and in frail older adults. Moreover, polypharmacy has been associated with the incidence of frailty in older adults independent of medical diagnoses. The mechanisms for the contribution of medicine use to frailty are plausible. There is a linear relationship between a number of medications and weight loss, impaired balance, poor nutritional status, and functional impairment. These are important clinical features of frailty. Future interventions striving to promote healthy aging and longevity should also aim to improve the management of frailty by considering medication withdrawal because reduction in medicine use has positive outcomes in older adults. Judicious prescribing, preserving the balance between the benefits and harms of medicines, may optimize functional abilities in frail adults or even prevent frailty.