Pamela Sardo, PharmD, B.S.


Pamela Sardo, PharmD, B.S., is a licensed pharmacist and Freelance Medical Writer at Sardo Solutions in Texas.


Topic Overview

Patients may be diagnosed with multiple chronic conditions that require the use of multiple medications to maintain or improve patient outcomes. This is known as polypharmacy. However, there are situations where the therapeutic benefits of multiple medications are outweighed by the harm the medications may cause to the patient. Harm includes adverse events and poor health outcomes. Polypharmacy occurs when patients have co-occurring physical and mental health conditions (e.g., diabetes and schizophrenia) or when a patient is frail and suffers from chronic pain. Strategies to reduce possible harmful effects of polypharmacy include rigorous patient-centered medication reviews and raising patient awareness about the risks of polypharmacy. Monitoring systems can also be used to capture polypharmacy data. Exploratory research and a multidisciplinary healthcare team approach are two methods to reduce the devastating effects of polypharmacy on individuals’ quality of life.


Accreditation Statement:


image LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.


Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity 

Pharmacist  0669-0000-23-051-H01-P

Pharmacy Technician 0669-0000-23-052-H01-T

Credits: 1 hour of continuing education credit


Type of Activity: Knowledge


Media: Internet, Home Study Fee Information: $4.99

Estimated time to complete activity: 1 hour, including Course Test and course evaluation


Release Date: March 25, 2023 Expiration Date: March 25, 2026


Target Audience: This educational activity is for pharmacists.


How to Earn Credit: From March 25, 2023, through March 25, 2026, participants must:


Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;”

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.


Learning Objectives: Upon completion of this educational activity, participants should be able to:


Describe what polypharmacy means in healthcare

Identify patient settings where polypharmacy can occur

List common therapeutics associated with polypharmacy

Describe safety concerns of polypharmacy and ways to minimize them




The following individuals were involved in the development of this activity: Pamela Sardo, PharmD, B.S., and Susan DePasquale, MSN, PMHNP-BC. Pamela Sardo, Pharm.D., B.S., was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.


ⓒ LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of LLC.



Patients may be diagnosed with multiple, chronic illnesses that necessitate the use of multiple medications to treat their conditions. This is especially true of elderly patients. Multiple drug prescribing has been labeled polypharmacy in some cases. Importantly, prescribing and dispensing multiple medications require clinicians to optimize the benefits and minimize the harms that may present. There are also situations where polypharmacy is inappropriate because the therapeutic benefits of concomitant medications may be outweighed by harm, such as adverse events and poor health outcomes. Strategies may be used to reduce the possible harmful effects of inappropriate polypharmacy. Monitoring systems can also be used to capture polypharmacy data. Exploratory research and a multidisciplinary healthcare team approach are two methods that may reduce the potential negative effects of polypharmacy on a patient’s quality of life.


History of Polypharmacy


Over the years, a number of prominent physicians, scientists, and organizations have studied the use of multiple medications to treat patients. More than one hundred years ago, Sir William Osler, who was known as the “Father of Modern Medicine” and America's best diagnostician,1 criticized his colleagues for treating patients with a ‘shotgun’ approach.2 Sir William Osler did not approve of clinicians focusing on a patient’s symptoms and managing each symptom separately, rather than looking at and treating the disease process.1,2


Almost 60 years ago, Dr. Louis Lasagna, a clinical pharmacology pioneer, identified drug reaction complications. He identified gastrointestinal bleeding associated with anticoagulants and salicylates, excessive sedation from barbiturates, and osteoporosis due to steroids.3


In 1992, a publication by 13 United States and Canadian experts identified 19 drugs that should generally be avoided and 11 doses, frequencies, or durations of use of specific drugs that generally should not be

exceeded in skilled nursing facilities.4 Dr. Beers and his colleagues revealed that 40% of residents received at least one inappropriate medication order, and 10% received two or more inappropriate medication orders concurrently. Seven percent of all prescriptions were deemed inappropriate. They concluded that inappropriate medication prescribing in nursing homes was common.4


In 1993, Dr. Beers convened a consensus panel to develop a list of potentially inappropriate medications for older adults in nursing homes. This original list was originally known as the Beers Criteria.5


In 2001, the Healthy People 2000 Final Review revealed adverse drug reactions were estimated to play a role in more than 100,000 deaths nationwide each year. Physiological changes associated with increasing age, specific diseases and conditions, and polypharmacy were attributed to an increased risk of an adverse outcome.5


In 2015, the American Geriatric Society (AGS) acquired ownership of the Beers Criteria and now publishes updated and expanded information known as the AGS Beers Criteria®. This report now includes all older adults and is no longer limited by location or type of clinical care.5-7 This evidence- based document includes information regarding the level of evidence used to make recommendations and the overall strength of a recommendation. This document is updated every three years as new data emerges.6,7


What is Polypharmacy?


There is no universally agreed-upon definition for the term polypharmacy.8 In literature, it is generally referred to as the use of 5 or more medications but it has also been applied to the use of 3 to 10 medications, or more.8 Polypharmacy is also used interchangeably with overprescribing, medication overload, multiple-drug consumption, excessive use of drugs, unnecessary drug use, inappropriate medication use, the “other” drug problem, and medication use without indication.3,4,8

Although numerical definitions of polypharmacy may be used, these definitions do not distinguish between polypharmacy and inappropriate prescribing of medications.8 Pharmacotherapy has benefitted patients globally and when multiple drugs are prescribed, the result does not necessarily lead to inappropriate or incorrect use of medications.9 Masnoon, et al. (2017), pointed out that numerical definitions of polypharmacy do not consider a patient’s specific comorbidities and this makes it difficult to assess the safety and appropriateness of pharmacotherapy in the clinical setting.8 For example, in cardiology, clinical practice guidelines state that three medications are often needed to manage heart failure or control blood pressure appropriately. In endocrinology, individuals with type 2 diabetes often require at least two medications for effective glucose control.9 In infectious disease guidelines, combination antibiotic regimens, with different modes of action, are often chosen to eliminate different pathogens or to manage drug-resistant bacteria. In psychiatry, antipsychotics may be multi-receptor compounds involving the dopaminergic and serotonergic systems or focus on the glutamatergic system.10 Pharmaceutical manufacturers have also developed combination medications in one form as a treatment option and for ease of patient use.


To help clarify the definition of polypharmacy, some scholars propose that polypharmacy should be defined as “the use of more medications than are medically necessary.” Under this definition, medications that are not indicated, not effective, or duplicative and unnecessary, would be considered polypharmacy.11 Other studies recommend adopting terms like “appropriate polypharmacy” versus “inappropriate polypharmacy” to distinguish between the proper use of multiple drugs and over-prescribing.8 This could help focus attention on patients who are prescribed too many drugs or drugs that are inappropriate for them and that lead to adverse events.


Prevalence and Risks of Polypharmacy


The use of polypharmacy is most common in older populations who tend to suffer more from multiple illnesses. These patients may take one or more medicines to treat each condition.8 Moreover, patients generally are taking larger numbers of medications, and this includes children and adolescents.8

In the United States, polypharmacy rates increased from 6.3% to 10.7% from 1999–2000 through 2007–2008.12 Gu, et al. (2010) reported that 36.7% of Americans 60 years of age or older are taking five or more prescription drugs.13 Moreover, 27.3 percent of older patients are taking 3 to 5 prescription drugs.13 Following this report, Kantor, et al. (2015) reported that prescription drug use had increased significantly among adults in the United States between 1999–2000 and 2011–2012.14 This included “a marked increase in polypharmacy. Specifically, the prevalence of prescription drug use increased from 51% in 1999–2000 to 59% in 2011–2012, while the prevalence of polypharmacy increased from 8.2% to 15%.”14 In 2019, this upward trend continued with the Centers for Disease Control and Prevention reporting that among U.S. adults aged 40–79, one in seven took a prescription drug in the past 30 days, and 22.4% used five or more prescription drugs in the past 30 days.15 This supports the view that polypharmacy increased from 6.3% to 22.4% over the past two decades, an increase of over 300%.


In some cases, older adults have been prescribed 10 or more medications. Jokanovic, et al. (2015) revealed 65% of long-term care residents received 10 medications.16 When over-the-counter products and supplements are included, the number of older individuals taking five or more medications increases greatly.17


Polypharmacy is associated with adverse outcomes.8 For example, the prescription of 5 medications is associated with a published risk of adverse outcomes such as falls, disability, drug interactions, nonadherence, reduced function, and mortality.8,9 Polypharmacy also leads to extended hospital stays and readmissions soon after discharge.8


There is also a correlation between the number of drugs a patient takes and the risk of adverse events and harm: the more drugs a person takes, the greater the risk of harm. Researchers have published that elderly patients prescribed two medications have a 6% chance of experiencing an adverse event, compared with 50% for patients prescribed five drugs and 100% for patients prescribed eight or more drugs.18 Qato, et al. (2008) found that older adults, who resided in community dwellings, commonly took prescription and

nonprescription medications together.17 They reported that nearly 1 in 25 of these individuals were at risk for a major drug-drug interaction.17


In addition, older patients are at greater risk of harm and adverse effects because they tend to have reduced renal and hepatic function, lower lean body mass, and poorer hearing, vision, cognition, and mobility.8


Common Settings for Polypharmacy


Polypharmacy is identified in a wide range of patient care settings. It is identified in community practice electronic medical records and pharmacy computer systems. It can also be revealed in hospitals, long-term care facilities, and many other settings.4,19-21 For example, the United States Nursing Home Survey found that 39.7% of residents up to age 84 had been prescribed multiple medications and that the rate of polypharmacy for patients aged 85 years or older was 34.8%.11


Comorbidities Commonly Seen in Polypharmacy


Causes of polypharmacy include physical and mental health conditions, such as diabetes or schizophrenia. Other complex conditions, such as frailty and chronic pain, also contribute to increased utilization of medications.


Physicians caring for patients with complex comorbidities report that current decision-support processes are inadequate to optimize benefits and minimize harm.22 Factors contributing to polypharmacy include patient- related, systems-related, condition-related, medication-related, or social issues. Patient-related issues often include multiple medical conditions managed by multiple subspecialists, having chronic mental health conditions, and residing in a long-term care facility. Systems-related factors contributing to polypharmacy include poorly updated medical records, automated refill services, and prescribing to meet disease-specific quality metrics.23 Condition- related risk factors include depression, dementia or cognitive decline, combinations of chronic mental and physical diseases such as diabetes and schizophrenia, individuals with frailty, and those with a history of falls.

Medication-related risks include drugs with a narrow therapeutic range, high potential for drug-drug interactions, and the need for constant monitoring. Social risk factors include not living independently, and a limited ability to understand treatment recommendations.24


Children and adolescents receiving multiple medications concurrently have recently increased. Few publications have analyzed polypharmacy in this vulnerable population. Combination therapy is often prescribed for attention- deficit/hyperactivity disorder (ADHD). For example, published studies include the appropriate use of a stimulant with an alpha-agonist for residual symptoms of ADHD. Published evidence of efficacy exists for prescribing a stimulant plus risperidone for comorbid aggression or disruptive behavior. Combination treatments; however, frequently yielded more side effects.25


Pharmacokinetics involves how a medication is processed in the body and includes absorption, distribution, metabolism, and excretion. Pharmacodynamics involves how the medications act on the body. When assessing polypharmacy, distribution is affected by age. Medications that are distributed predominantly in skeletal muscle (e.g., digoxin) must be adjusted for age-related atrophy. Weight is also usually lower in older adults, and weight-based dosage adjustments are indicated for many medications (e.g., low-molecular-weight heparin (LMWH]).26


Many patients self-medicate by purchasing OTC medicines, such as nonsteroidal anti-inflammatory agents (NSAIDs), or medications for allergies and coughs. These may interact with prescribed medications and may cause harm. In some cases, patients may also be sharing prescription medicine with other individuals. Therefore, it is important to ask patients about the use of all types of medicines or remedies.27 The use of herbal medicine is often taken with prescribed medicine. Healthcare providers and pharmacy team members should ask patients if they use traditional and complementary medicines because herbal–drug interactions are possible and may cause a patient safety risk.27

Frequent Therapeutic Classes of Medications in Polypharmacy


Three classes of medications are reported to contribute to 60% of emergency visits for adverse drug reactions among older adults. These are anticoagulants, medications for patients with diabetes, and opioids.13 Additional therapeutic classes with the potential for harmful side effects include sedative-hypnotics, OTCs, medications for patients with hypertension, and antipsychotics.8


The World Health Organization (WHO) recommends attention be given to high-alert medications with polypharmacy.27 High-alert medications are drugs with a heightened risk of causing significant patient harm when they are used in error.28 Table 1 contains examples of high-alert, high-risk medications that should be monitored on an individual basis as polypharmacy.


Table 1

Select Classes or Categories of High Alert Medications

Adrenergic agonists, IV (e.g., epinephrine, phenylephrine, norepinephrine)
Adrenergic antagonists, IV (e.g., propranolol, metoprolol)
Antiarrhythmics, IV (e.g., lidocaine, amiodarone)


-anticoagulants (e.g., warfarin, low molecular weight heparin, unfractionated heparin)

-direct oral anticoagulants and factor Xa inhibitors (e.g., dabigatran, rivaroxaban, apixaban, edocaban, betrixaban, fondaparinux)

-thrombolytics (e.g., alteplase, reteplase, tenecteplase)

Dialysis solutions, peritoneal and hemodialysis)
Inotropics, IV (e.g., digoxin)
Insulin, subcutaneous and IV
Moderate sedation agents, IV (e.g., midazolam, lorazepam)
Moderate and minimal sedation agents for children, oral (e.g., lorazepam, midazolam)





Parenteral nutrition preparations
Sulfonylurea hypoglycemics (e.g., glyburide, glipizide)


Table 1 is taken from ISMP list of high-alert medications (2018)28


Researchers have published that a “prescribing cascade” may begin when an adverse drug reaction is misinterpreted as a new medical condition, for which another drug is then prescribed. This increases the possibility of additional adverse effects relating to this potentially unnecessary treatment. Possible adverse effects reported in “prescribing cascade” cases may include orthostatic hypotension, anticholinergic reactions, sedation, or cardiac conduction disturbances. It is prudent to consider these complications to prevent polypharmacy and associated negative outcomes.29


Considerations to Reduce Polypharmacy


Traditional disease-oriented guidelines are often inadequate when comorbidities and polypharmacy are present. Clinical decision-making becomes complicated in these situations.24


Strategies to reduce possible harmful effects of polypharmacy include rigorous patient-centered medication reviews and raising patient awareness about the risks of polypharmacy. The National Institute of Health (NIH) and National Institute on Aging recommend that deprescribing should be part of a clinician’s patient-centered care.30


Medication reviews are useful to manage polypharmacy. These reviews are discussed in polypharmacy guidance documents as a solution to optimize therapeutic regimens in patients with comorbid conditions and for comprehensive patient care. The reviews are a structured evaluation of patients’ medicines to optimize or improve health outcomes.27 For example, a clinician should evaluate whether a patient needs gabapentin, a nonsteroidal anti-inflammatory (e.g., diclofenac), and acetaminophen with codeine concurrently. Table 2 contains considerations within a medication review.

Commonly used tools that can help reduce polypharmacy include the Beers Criteria, the Screening Tool to Alert doctors to the Right Treatment (START), and the Screening Tool for Older Person's potentially inappropriate Prescriptions (STOPP). START focuses on ensuring that appropriate medications with likely benefits are not omitted in error. The Beers Criteria and STOPP tools strive to minimize exposure to medications that have risks possibly outweighing potential benefits.7,31


Table 2

Step-by-step approach to a patient-centered medication review


AimsWhat matters to the patient?Review diagnoses and objectives:
NeedIdentify essential medications

Identify essential medications (not to be stopped without specialist advice):

(e.g., medications for Parkinson’s disease)

Are unnecessary medications


Identify and review the need for medications:
EffectivenessAre therapeutic objectives achieved?Identify the need for adding/intensifying medications to achieve objectives:

Is there risk of adverse drug


Check for patient safety risks:

Understand medication goals

Manage existing problems

Prevent future problems

Medications with essential functions (e.g., thyroxine, antidiabetic medication, atenolol)

Medications preventing symptom decline

With temporary indications

With high maintenance doses

With limited benefit for the indicated use

For symptom control

To achieve biochemical/clinical targets

To prevent disease progression/exacerbation

Drug–disease interactions

Drug–drug interactions

Robustness of monitoring mechanisms for high-risk medications

Risk of accidental overdose

residents in a care home setting

patients on high-risk (high-alert) medications

patients taking multiple medications

patients with two or more comorbidities

patients who are frail

patients with dementia

Appropriate polypharmacy should be addressed at the point of initiation of new medicines. Discussion of treatment plans and therapeutics should occur during medication reviews and within settings where there is a transition of care. A transition of care can occur from higher intensity care (e.g., hospital setting) to lower intensity care (e.g., discharge to outpatient). It can also occur from lower intensity care to higher level care. Process enhancements should include data monitoring systems to identify issues, provide computer alerts, and measure improvement.27


What is Next in the Management of Polypharmacy?


Reducing inappropriate or unnecessary medications can significantly reduce hospitalization, physiological distress, the use of healthcare resources, mortality, and healthcare costs8 Physicians report four problem areas in the management of multiple comorbidities. These areas include fragmentation of healthcare, the inadequacy of guidelines and evidence-based medicine, challenges in delivering patient-centered care, and barriers to shared decision- making.22


In, entering the term polypharmacy as a keyword search, retrieved 168 studies.32 One trial is assessing the clinical and economic effectiveness of a pharmacogenomic approach to prescribing medications in patients with high-risk polypharmacy. The participant will collect a genetic sample with a mouth swab. Genetic testing, data analysis, and clinical interpretation will help prescribers select treatments based on evidence-based predictions of patient drug response and tolerance. The primary objective is to determine changes in healthcare expenditures and hospitalization, emergency room visits, medical office visits, and telephone encounters after the pharmacogenomics test and counseling of the prescribers by a study pharmacist.33


Exploratory research and a multidisciplinary healthcare team approach are two methods that may be used to reduce the devastating effects of polypharmacy on an individual’s quality of life. Researchers are implementing a clinical trial titled Aligning Medications with What Matters Most

(ALIGN). In this National Institute on Aging (NIA)-funded study, a clinical pharmacist collaborates with a primary care provider. The pharmacist will provide information by mail and conduct telehealth visits with individuals living with dementia, and their partners in care. The goal is to align medications with the overall goals of care. This trial strives to develop interventions that improve communication between clinicians and older adults and their families. To reduce polypharmacy, the pharmacist will make recommendations to the primary care provider to discontinue a medication that is not necessary.34,35


A structured evaluation of a patient’s medicines remains an unmet medical need and is necessary to address polypharmacy. The aim of multidisciplinary teams of healthcare professionals addressing polypharmacy is to optimize medication therapy and improve health outcomes and quality of life. This entails detecting drug-related problems and recommending interventions to minimize the risk of adverse outcomes such as falls, frailty, disability, and mortality. Pharmacy team members are well-positioned to contribute to the management of polypharmacy.




The use of polypharmacy has been rising over the past decades in all age groups. It is more prevalent in older populations who tend to suffer more from multiple illnesses. Appropriate polypharmacy should be addressed at the point of initiation of new medicines. Medication reviews are useful to manage polypharmacy. These reviews are discussed in polypharmacy guidance documents as a solution to optimize therapeutic regimens in patients with comorbid conditions and for comprehensive patient care. Discussion of treatment plans and therapeutics should occur during medication reviews and within settings where there is a transition of care. Commonly used tools that can help reduce polypharmacy include the Beers Criteria, the Screening Tool to Alert doctors to the Right Treatment (START), and the Screening Tool for Older Person's potentially inappropriate Prescriptions (STOPP).

Course Test


What concepts are associated with polypharmacy in healthcare?


It is not always inappropriate or incorrect

It can sometimes be referred to as overprescribing

It can sometimes be referred to as medication overload

All of the above are correct regarding polypharmacy


In which two practice settings is polypharmacy commonly identified?


Acupuncture office and community pharmacy

Hospitals and long-term care

Ultrasound clinic and nursing home

Pharmacy computer records and massage therapy


Which classes of medications are among those reported to contribute to 60% of emergency visits for adverse reactions in older adults?


Topical steroid creams and anticoagulants

Peroxide ear drops and diabetes medication

Anticoagulants and opioid medications

OTC eye drops and topical steroid creams


What is/are reported safety concern(s) when an individual takes 5+ medications?


Falls and nonadherence

Disability and reduced function

Drug interactions and mortality

All of the above have been reported


Which statement most accurately reflects a strategy to minimize polypharmacy?


Perform a medication review as a structured evaluation of patients’ medicines

Use STOPP tools to ensure inappropriate medications continue

Use Beers’ Criteria to ensure drugs for temporary indications continue

Involving the patient is only necessary for hospitalizations

What is an example of appropriate polypharmacy?


In cardiology, the use of more than 1 medication is very rare

In cardiology, 3 medications may be needed to manage heart failure

In endocrinology, type 2 diabetes means 2 antibiotics are required

In psychiatry, use 2 medications to eliminate pathogens


Which statement below is a reported fact about polypharmacy?


Nearly 30% of young adults are prescribed 10+ medications.

Among U.S. adults aged 40–79, 22.4% used five or more prescription drugs in the past 30 days.

Data shows that the number of persons taking 5+ medications has decreased over the past 10 years.

The number of older people taking 5+ medications does not change when over-the-counter drugs are included in the data.


An older patient has recently moved to your city, is taking multiple medications, and asks about supplements. Which information should be included in the patient counseling?


Let the pharmacy know before you purchase any sunscreen with multivitamins

Consult a provider before taking a herbal supplement to minimize the risk of interactions

It is permissible to use any OTC except for St. Johns Wort with prescription medications

Don’t worry about interactions if supplement use is limited to 4 days a week.

A 58-year-old has a medical history of type 2 diabetes (HbA1c=10%), coronary heart disease, hypertension (BP 150/85 mm Hg), atrial fibrillation, chronic obstructive pulmonary disease, chronic pain, depression, and hypothyroidism. The patient’s current medications include Aspirin, Lisinopril, Metformin, Amlodipine, Pioglitazone, Atenolol, Levothyroxine, Gabapentin, Citalopram, Acetaminophen w/ codeine, Diclofenac, and Omeprazole. Which medication(s) might be considered essential and is/are not to be stopped without specialist advice?




Antidiabetic medication

All of the above


The same patient, a 58-year-old with a medical history of type 2 diabetes (HbA1c=10%), coronary heart disease, hypertension (BP 150/85 mm Hg), atrial fibrillation, chronic obstructive pulmonary disease, chronic pain, depression, and hypothyroidism is taking Aspirin, Lisinopril, Metformin, Amlodipine, Pioglitazone, Atenolol, Levothyroxine, Gabapentin, Citalopram, Acetaminophen w/ codeine, Diclofenac, and Omeprazole. Which question below might be asked to the physician and/or patient to determine if polypharmacy can be reduced?


Have you had any infections, viruses, or received immunizations lately?

Regarding medications for pain, is gabapentin for neuropathic pain or mechanical pain and what is the level of pain control?

Do you need any OTCs or vitamins while you are here today?

Since some medications upset the stomach, are you taking antacids or medication for constipation?



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Aligning medications with what matters most (ALIGN). Updated June 21, 2022. Accessed February 22, 2023



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