EPIDEMIOLOGY OF AGING (K LAPANE, SECTION EDITOR) Frailty and Unintended Risks of Medications David B. Hogan 1 & Colleen J. Maxwell 2 # Springer Nature Switzerland AG 2020 Abstract Purpose of Review In this narrative review, we focus on aspects of the complicated relationship between frailty and medications that we feel would be of particular interest to researchers and health care practitioners. Recent Findings Frailty and polypharmacy (≥5 medications) are inter-related with evidence of a bidirectional potentially casual relationship. Medication review and withdrawal of potentially inappropriate medications is frequently advised for the manage- ment of frailty. Changes in the pharmacokinetics and pharmacodynamics of drugs with frailty are felt to parallel those seen with aging though possibly more pronounced. While both frailty and polypharmacy are associated with adverse outcomes, recent research suggests that relative measures of associated risk may be blunted among older adults with frailty compared to non-frail older adults. Summary Research on drug therapy in later life should include a consideration of frailty and how changes in frailty status may affect the balance between benefit and risk with pharmacotherapy. Keywords Frailty . Medications . Older adults . Adverse drug reactions . Health outcomes Introduction Our understanding of the relationship between frailty and medications is an evolving one. In this narrative review, we focus on recent research addressing this area that would be of particular interest to epidemiologists and relevant to practi- tioners. We start with brief overviews of frailty and drug use by older persons before moving on to the association between them. Frailty Frailty is a state of increased vulnerability to stressors (includ- ing medications) arising from impairments in multiple physio- logical systems leading to declines in homeostatic reserve [1•]. It is a way to appreciate the variable resilience of older individ- uals, over and above their age, sex, and comorbidity level [2]. Many unresolved questions persist about its detection, patho- physiology, and relationship with aging, disability, and multi- morbidity [3]. Regardless of the particular frailty measure employed, higher levels of frailty have consistently been asso- ciated with a heightened risk for death, institutionalization, hos- pitalization, falls, and poorer quality of life [4••, 5•, 6•]. A number of approaches to its detection have been pro- posed. Their diversity reflects the multifaceted nature of frailty in later life, as well as the unique perspective taken by indi- vidual researchers. The various measures can be categorized as follows: (i) judgment-based (e.g., Canadian Study of Health and Aging (CSHA) clinical frailty scale); (ii) single measures of physical performance (e.g., gait speed); (iii) broader mea- sures of physical frailty (e.g., Cardiovascular Health Study (CHS) criteria, Study of Osteoporosis Fractures (SOF) scale); (iv) multidimensional tools (e.g., FRAIL, Edmonton Frail Scale (EFS)) [7•]; and, (v) indices of accumulated health def- icits (e.g., frailty index or FI) [8]. Which instrument is used to detect frailty in older populations will influence how many This article is part of the Topical Collection on Epidemiology of Aging * Colleen J. Maxwell colleen.maxwell@uwaterloo.ca David B. Hogan dhogan@ucalgary.ca 1 Department of Medicine, Division of Geriatric Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada 2 Schools of Pharmacy and Public Health and Health Systems, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada Current Epidemiology Reports https://doi.org/10.1007/s40471-020-00226-5