Refining the Definition of Polypharmacy and Its Link to Disability in Older Adults: Conceptualizing Necessary Polypharmacy, Unnecessary Polypharmacy, and Polypharmacy of Unclear Benefit


Eric A Lee, MD1; Jeffrey W Brettler, MD1; Michael H Kanter, MD2;
Steven G Steinberg, MD3; Peter Khang, MD4; Christopher C Distasio, MD5;
John Martin, MD6; Mark Dreskin, MD7,8; Nolan H Thompson, MD9;
Timothy M Cotter, MD10; Kim Thai, MD11; Lyn Yasumura, MD12;
Nancy E Gibbs, MD13

Perm J 2020;24:18.212 [Full Citation]
E-pub: 12/11/2019


The term polypharmacy in older adults is generally used in a pejorative context in the medical literature. Because of its link to geriatric syndromes and disability, the avoidance of polypharmacy is usually recommended in older adults as a strategy to optimize functional status. However, there are many polypharmacy regimens based on high-quality trials that clearly reduce the risk of disability in older adults. Other guidelines for older adults recommend the use of additional medications that may or may not be evidence based and that may or may not reduce disability. Therefore, we propose that, in the geriatric literature, polypharmacy now be categorized as “necessary polypharmacy,” “unnecessary polypharmacy,” or “polypharmacy of unclear benefit.” In this article, we discuss the 3 categories of polypharmacy and give examples on each polypharmacy regimen and its potential relationship to disability in older adults.


Older adults, or patients older than 65 years, have diminished reserve capacity, or the physiologic plasticity to adapt, compared with their younger counterparts. Throughout the heterogeneous continuum of geriatric aging (from the robust marathoner to the prefrail patient using a cane to the frail bedbound nursing home resident), older adults have less lean body mass with increased body fat; are more likely to have renal, hepatic, and cardiac insufficiency; take more prescriptions medications on average; and tend to have more medical problems than their younger counterparts. Older adults often experience symptomatic drug toxicity that would not have been felt by their younger counterparts. The more medications an older adult receives, the more susceptible s/he is to these drug-drug, drug-disease, and drug-patient interactions. In older adults, these adverse drug reactions often can be subtle, such as somnolence or restricted activity. Other times they are overt, for example, a fall with hip fracture or symptomatic hypoglycemia. Whether insidious or sudden, drug toxicity leads to substantial morbidity to older adults.

Polypharmacy in patients older than 65 years (ie, “older adults”) is generally defined as taking 5 or more prescription medications.1 About 4 in 10 older adults are on polypharmacy regimens.2 In the geriatric literature, polypharmacy is considered a risk factor for functional decline, leading to dependence on others. Interventions to reduce polypharmacy are considered critical strategies to prevent disability in older adults.3-5 Classical geriatric teaching emphasizes minimizing the use of prescription medications, especially in older adults at risk of frailty. The addition of 1 prescription medication—whether the older patient was previously receiving no medications or 4 medications—can lead to substantial adverse drug events that might lead to disability.

Simplistically, major root causes of functional decline in the last year of life in older adults can be divided into at least 4 categories: Disability owing to advanced cancers, primary neurologic disorders, organ failure, and frailty.6,7 We will focus on the last 3 mechanisms of disability and their positive or negative relationship with polypharmacy.

We believe that the current definition of polypharmacy, with its negative connotations, is outdated. The definition of polypharmacy should be more nuanced. Recent trials have demonstrated that appropriate polypharmacy regimens can prevent disability in older adults.8-11 Hence, we believe that polypharmacy should be classified as “necessary polypharmacy” (NP), “unnecessary polypharmacy” (UP), or “polypharmacy of uncertain benefit.”

NP regimens should be considered additional medications that can optimize functional status and prevent disability in older adults. For older patients receiving NP regimens, the benefits outweigh the risks. Initiation and continued adherence are critical in this category. The prescribing of and continued adherence to these regimens indicate high-quality care.

In contrast, UP should be considered additional medications that put older adults at higher risk for the development of disability. For older patients receiving these regimens, the risks outweigh the benefits. Noninitiation of these medication regimens is preferred. Deprescribing is critical in this category. Both noninitiation and deprescribing indicate high-quality and thoughtful care.

Polypharmacy of uncertain benefit should be considered additional medications in which the research is unclear on whether the harms balance the benefits. Weighing the potential risks with the possible benefits must be thoughtfully considered, and shared decision making with the patient is critical before finalizing the medication regimen.

NP regimens are generally used in the prevention or treatment of organ failure caused by cardiovascular disease. However, NP regimens have been recommended for the prevention of disability caused by primary neurologic diseases and geriatric syndromes as well.

The prevalence of dementia is nearly 9% of individuals older than age 65 years.12 In 2017, the Lancet Commission on dementia care recommended the active treatment of hypertension in adults age 35 years and older as a key intervention to prevent dementia.13 Also in 2017, the National Academy of Medicine recommended that the appropriate treatment of hypertension could prevent, delay, or slow clinical Alzheimer-type dementia.14 Appropriately aggressive polypharmacy with antihypertensive medications in older adults with hypertension is a key component to prevent disability caused by dementia.

Subgroup analysis using Systolic Blood Pressure Intervention Trial (SPRINT) data demonstrated that appropriately aggressive control of blood pressure will reduce disability caused by cardiovascular disease.8 Using the automated office blood pressure (AOBP) technique, 2636 patients older than age 75 years (with major exclusion criteria; see Sidebar: Exclusion Criteria for Patients from SPRINT) were randomized to an AOBP systolic pressure target below 140 mmHg (equivalent to a systolic blood pressure of about 150 mmHg using the traditional office-based technique of sphygmomanometry) in the standard treatment group or an AOBP systolic blood pressure of less than 120 mmHg (equivalent to a systolic blood pressure of about 130 mmHg using the traditional blood pressure measurement technique) in the intensive treatment group. On average, older patients needed 2.1 antihypertensive medications to achieve the AOBP systolic blood pressure target of 140 mmHg in the standard treatment group and 2.9 medications to achieve the AOBP systolic blood pressure target of 120 mmHg for the intensive treatment group. The number needed to treat in 3.14 years in the intensive regimen was 27 to prevent any cardiovascular event (myocardial infarction, cerebrovascular accident, acute coronary syndrome, cardiovascular death) compared with the standard therapy.8


Concerns regarding adverse effects of these antihypertensive polypharmacy regimens have been tempered with the results of the SPRINT subgroup analysis, of which more than 30% of study participants were considered frail.8 The subgroup analysis showed that there was no absolute increased risk of injurious falls and no statistical difference in orthostatic hypotension in the intensive treatment group compared with the standard treatment group. In addition, there was no difference in gait speed, a proxy of frailty in the geriatric population.

Therefore, given the safety of hypertensive polypharmacy regimens and their proven benefits, we recommend a minimum blood pressure goal of less than 140/90 mmHg using the traditional blood pressure measurement in adults older than age 65 years. For older patients with established cardiovascular disease, chronic kidney disease with an estimated glomerular filtration rate between 20 mL/min/1.73 m2 and 59 mL/min/1.73 m2, or with a 10-year Framingham Risk Score of greater than 15% (or a 10-year American College of Cardiology/American Heart Association Pooled Cohort Equation Risk Score > 15% or a Kaiser Permanente A Risk Score > 10%), we recommend consideration of a blood pressure goal of less than 130/90 mmHg using traditional blood pressure measurements in noninstitutionalized, ambulatory patients.

NP regimens also have a role in prevention of disability caused by geriatric syndromes. An example might include the use of bisphosphonates, calcium, and vitamin D for the treatment of established osteoporosis. Appropriate use of alendronate has been shown to have a risk reduction of future fractures, including hip fractures, by nearly 50%.15

Conversely, UP regimens increase the risk of disability because of their strong association with the development of geriatric syndromes.3-5 Adverse drug reactions from UP regimens lead to unplanned hospitalizations, a risk factor for functional decline in older adults.16,17 UP regimens have been linked with the development of primary neurologic disorders.18 Finally, UP contributes to increased risk of disability by leading to poor medication reconciliation from clinicians and consequently less adherence to NP regimens.

We posit 11 common scenarios of UP regimens in older adults (Table 119-55). They can be considered medication errors that put the patient at higher risk of disability. Unnecessary polypharmacy regimens are a sign of poor prescribing quality.

Finally, polypharmacy of uncertain benefit occurs when risks vs benefits either negate each other or are unclear in relative magnitude. Shared decision making with the patient is paramount in these situations. An example of polypharmacy of uncertain benefit might include the off-label use of gabapentin for the treatment of painful neuropathy. Even if gabapentin improves the quality of life in an older adult by efficaciously reducing painful neuropathy, nearly 1 in 5 will experience dizziness, 1 in 7 will experience somnolence, and 1 in 7 will experience gait disturbances  at doses at or above 1200 mg daily in adults of all ages.32 Somnolence and dizziness are the top contributors of restricted activity in older adults,56 a risk factor for future disability.17 Gait impairment is a risk factor for falls.4

Another example includes the use of proton pump inhibitors (PPIs) in older adults receiving aspirin and clopidogrel (and with no history of peptic ulcer and/or not receiving concurrent corticosteroids, anticoagulants, or nonsteroidal anti-inflammatory drugs). The American College of Cardiology and the American Heart Association state that it is “reasonable” to use PPIs for these patients of “advanced age” who are receiving aspirin and clopidogrel therapy.24 Whether the reduction in peptic ulcer risk with the use of PPIs in this setting balances the increased risk of infections26 and osteoporotic fractures27 is not established.

We recognize that guidelines have been created for medication appropriateness by expert groups from all medical specialties that influence how physicians prescribe to older adults (see Sidebar: Consensus Statement on Polypharmacy). Controversy has shrouded guidelines because of the diversity of function in adults older than age 65 years and because of publication biases. Although we recognize that the theme of 1 size fits all will never apply to all patients older than age 65 years, exceptions should be minimized. Initiating UP or not initiating NP as well as refilling UP and not deprescribing UP can have monumental consequences for risk of future disability. Shared decision making should always occur in discussions with older patients with a focus on the risk/benefit ratio of NP, UP, and polypharmacy of uncertain benefit.

Language shapes how we think and act. Among geriatricians, the term polypharmacy has a negative connotation and suggests needlessly putting older adults at higher risk of harm. We must update this antiquated definition of polypharmacy by refining the term as NP, UP, or polypharmacy of uncertain benefit. Not all polypharmacy should be avoided, and in many circumstances, polypharmacy should be recommended. In older adults, superior prescribing performance reflects the appropriate noninitiation and deprescribing of UP, the appropriate initiation and continuation of NP, and thoughtful consideration of polypharmacy of uncertain benefit.


Disclosure Statement

The author(s) have no conflicts of interest to disclose.


Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

How to Cite this Article

Lee EA, Brettler JW, Kanter MH, et al. Refining the definition of polypharmacy and its link to disability in older adults: Conceptualizing necessary polypharmacy, unnecessary polypharmacy, and polypharmacy of unclear benefit. Perm J 2020;24:18.212. DOI:

Author Affiliations

1 Department of Internal Medicine, West Los Angeles Medical Center, CA

2 Department of Clinical Science, Kaiser Permanente School of Medicine, Pasadena, CA

3 Department of Family Medicine, Panorama City Medical Center, CA

4 Department of Geriatrics, Palliative Medicine, and Continuing Care, Los Angeles Medical Center, CA

5 Department of Neurology, South Bay Medical Center, Harbor City, CA

6 Department of Internal Medicine, Los Angeles Medical Center, CA

7 Department of Integrated Behavioral Health, Los Angeles Medical Center, CA

8 Urgent Care Division, Los Angeles Medical Center, CA

9 Department of Psychiatry, Panorama Medical Center, CA

10 Department of Cardiology, Baldwin Park Medical Center, CA

11 Department of Physical Medicine and Rehabilitation, Baldwin Park Medical Center, CA

12 Department of Obstetrics and Gynecology, Baldwin Park Medical Center, CA

13 Department of Geriatrics, Kaiser Permanente Southern California, Pasadena, CA

Corresponding Author

Eric A Lee, MD (

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Keywords: aging adults, deprescribing in older adults, disability in aging adults, drug-disease interactions, drug-drug interactions, drug-patient interactions, polypharmacy prescribed to aging adults


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