Challenges with Polypharmacy in the Geriatric Population

April 9, 2024

By Olivia Descorbeth

Peer Reviewed

As individuals advance in age, they tend to accumulate medical conditions that require a bevy of pharmaceutical treatments to manage. As a result, polypharmacy, generally defined as the use of five or more medications simultaneously, is relatively common, with a 37% prevalence in the geriatric population, and this estimate is likely much higher in inpatient and nursing home settings.1 The pervasiveness of polypharmacy is further compounded by the self-administration of over-the-counter and homeopathic medicines.

The notion of physical frailty in geriatric medicine attempts to quantify the impact that changing metabolism and organ function have on mortality.2 This mortality risk is associated with a diminished ability to endure environmental and biological stressors, leading to injury, sensory deficits, and functional dependence.3 Polypharmacy, especially when applied inappropriately, is known to contribute to physical frailty, and this frailty has been strongly associated with cognitive impairment.4,5 The connection is especially concerning, given that individuals with mild cognitive impairment are up to four times more likely to develop dementia, the seventh leading cause of death in the US.6,7

Although the connection between cognitive impairment and polypharmacy has been widely observed, the physiologic underpinnings of the connection are not well understood. One prominent theory focuses on the role of drug-drug interactions in increasing anticholinergic toxicity risk for older adults. Anticholinergic drugs are used to treat many conditions that are commonly observed in the geriatric population, including COPD (tiotropium), Parkinson’s disease (benztropine), insomnia (diphenhydramine), and urinary incontinence (oxybutynin).8 As people age, they experience a delayed onset of drug action and a decline in their ability to effectively clear medications, allowing for more drug-drug interactions as these agents linger in the body.9 As a result, elderly people are particularly vulnerable to adverse drug reactions. Anticholinergic toxicity is known to cause delirium, often with agitation and hallucinations, in geriatric populations.10 This effect is particularly alarming when considering the significant link between delirium and accelerated cognitive decline.11 One cohort study found that older adults taking anticholinergic drugs had a significant decline in cognitive function compared to controls, and this effect was stronger for those who possessed the apolipoprotein ε4 allele.7

The threat of drug-drug interactions extends beyond anticholinergic drugs to include GABA-aminergic and antidopaminergic agents, which also increase older patients’ risk of dementia.12 These limitations pose a unique challenge to managing medications for psychiatric conditions in the geriatric population. Aging is associated with unique psychological stressors that make the elderly more likely to develop mental illnesses.13 In addition, night-time agitation and delirium are common indications for the introduction of anti-psychotic medication in older adults.

Simplifying medication regimens and mitigating the risk of cognitive impairment should be pursued as much as possible. However, attempts to avoid polypharmacy can have their own deleterious effects. Undertreatment, the administration of medications at subtherapeutic levels, leads in psychiatric conditions to the persistence of subacute or more nuanced symptoms that can interfere with one’s instrumental activities of daily living. Because the assessment of therapeutic benefit in this context can be largely subjective, establishing effective dosing of psychiatric medication in the setting of complex comorbidities serves as a major obstacle to mental healthcare. Older individuals also tend to have atypical psychiatric presentations that are often mistaken with normal aging, obfuscating symptom severity and allowing for more pervasive undertreatment. Additionally, the treatment of physical conditions tends to take priority in medical management, likely because their improvement can generally be tied to more objective markers.

Although an optimal path toward limiting polypharmacy while avoiding undertreatment is still unclear, the problem could be helped by further inclusion of geriatric patients in clinical research. Elderly individuals have been historically excluded from clinical trials, largely due to comorbidities that render these patients unable to meet the inclusion criteria for many studies.14 The role of ageism in this issue should also be acknowledged, as the importance of including this population may be undervalued due to bias. Some organizations have taken steps to address the issue of polypharmacy in geriatrics directly. The American Geriatrics Society recently updated its “Beers criteria” list of medications that should be limited or avoided in elderly populations, and their guidelines have been vital in advising practitioners as they prescribe medications to older patients.15 However, the complexity of geriatric cases leads to these directives being routinely violated in order to align medical care with patient priorities.16 The lack of relevant data in the literature leaves geriatric providers to make more subjective judgments on how to approach pharmaceutical management. Until stronger evidence can be compiled, the “start low and go slow” principle that prevails in the field of geriatrics allows for necessary caution and flexibility in geriatric medication management.17

Olivia Descorbeth is a Class of 2025 medical student at NYU Grossman School of Medicine

Peer reviewed by Michael Tanner, MD, Associate Editor, Clinical Correlations, Professor, Department of Medicine at NYU Grossman School of Medicine

Image courtesy of Craig from Glasgow, Scotland, CC BY 2.0 <>, via Wikimedia Commons


  1. Delara M, Murray L, Jafari B, et al. Prevalence and factors associated with polypharmacy: a systematic review and meta-analysis. BMC Geriatr. 2022;22(1):601.
  1. Ruiz M, Cefalu C, Reske T. Frailty syndrome in geriatric medicine. Am J Med Sci. 2012;344(5):395-398.
  1. Lyu H, Wang C, Jiang H, Wang P, Cui J. Prevalence and determinants of frailty in older adult patients with chronic coronary syndrome: a cross-sectional study. BMC Geriatr. 2021;21(1):519.
  1. Bonfiglio V, Umegaki H, Kuzuya M. Potentially inappropriate medications and polypharmacy: a study of older people with mild cognitive impairment and mild dementia. J Alzheimers Dis. 2019;71(3):889-897.
  1. Clague F, Mercer SW, McLean G, Reynish E, Guthrie B. Comorbidity and polypharmacy in people with dementia: insights from a large, population-based cross-sectional analysis of primary care data. Age Ageing. 2017;46(1):33-39.
  1. Alzheimer’s Association. 2010 Alzheimer’s disease facts and figures. Alzheimers Dement. 2010;6(2):158-194.
  1. Threapleton CJ, Harris T, Baker EH. Stratifying patients for polypharmacy interventions: The case for a new biomarker? Br J Clin Pharmacol. 2022;88(4):1515-1517.
  1. Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry. 2001;62 Suppl 21:11-14.
  1. Chippa V, Roy K. Geriatric cognitive decline and polypharmacy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2023 Apr 16.
  1. Tune LE, Egeli S. Acetylcholine and delirium. Dement Geriatr Cogn Disord. 1999;10(5):342-344.
  1. Davis DHJ, Muniz-Terrera G, Keage HAD, et al; Epidemiological Clinicopathological Studies in Europe (EClipSE) Collaborative Members. Association of delirium with cognitive decline in late life: a neuropathologic study of 3 population-based cohort studies. JAMA Psychiatry. 2017;74(3):244-251.
  1. Kingston P, Le Mesurier N, Yorston G, Wardle S, Heath L. Psychiatric morbidity in older prisoners: unrecognized and undertreated. Int Psychogeriatr. 2011;23(8):1354-1360.
  1. Varma S, Sareen H, Trivedi JK. The geriatric population and psychiatric medication. Mens Sana Monogr. 2010;8(1):30-51.
  1. Bugeja G, Kumar A, Banerjee AK. Exclusion of elderly people from clinical research: a descriptive study of published reports. BMJ. 1997;315(7115):1059.
  1. 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081.
  1. Roth MT, Weinberger M, Campbell WH. Measuring the quality of medication use in older adults. J Am Geriatr Soc. 2009;57(6):1096-1102.
  1. Moore AR, O’Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging. 1999;15(1):15-28.