Published November 13, 2023

Unlocking Pandora's Pillbox: The Importance of Understanding Polypharmacy as an NP or PA

Picture this: you wake up, reach for your morning coffee, and then proceed to down a handful of pills. Sound familiar? In the United States, this scenario plays out every day for a staggering number of people, particularly those over 65. There can be a dark side to this routine, one that lands 750 older Americans in the hospital every day due to serious side effects from their medication cocktail. Over the past decade, adverse drug events in older people have led to a staggering 35 million emergency department visits and 2 million hospital admissions. While polypharmacy in children is under-studied and needs more research, it is a growing issue. In one study looking at a medication reconciliation program of 2.7 million clinic visits, about 26 percent of those pediatric patients had one or two medications.

Polypharmacy is a complex and significant issue in primary care in which nurse practitioners (NP) and physician assistants (PA) play a significant role. Their roles encompass not only prescribing medications but also optimizing regimens, educating patients, and ensuring patient safety in the context of polypharmacy. Below we will address the basics of polypharmacy for NPs and PAs. If you’d like a more thorough review, enroll in Primary Care Bootcamp for NPs and PAs to view “Polypharmacy in Complex Patients.” 

What is Polypharmacy?

The term "polypharmacy" is commonly defined as the daily consumption of five or more medications. However, there is little consensus on the definition. In 2018, a literature review unveiled a staggering 203 definitions across 162 studies. The different definitions can depend upon several factors, including whether the medications are concurrent or sequential, the duration of the therapy in adults, and whether the person is an adult or a child. In children, the number is often lowered from five medications daily to two medications.

Polypharmacy vs. Medication Overload: A Fine Line

Some clinicians also make a distinction between polypharmacy and medication overload. Polypharmacy means taking multiple medications at a time and can be helpful or harmful, whereas medication overload implies more harm than benefit.

Prescribing Cascade: When One Pill Begets Another

Another important concept in polypharmacy is the prescribing cascade. The prescribing cascade occurs when you prescribe one drug that causes an adverse drug event, which is either then treated with a prescription of another drug or drugs, or the event is misdiagnosed as a new medical problem, and then more medications are prescribed.

Why is Polypharmacy so Harmful?

Polypharmacy affects all ages, backgrounds, and health conditions. It's a silent, creeping menace, unleashing adverse drug effects, increasing the risk of falls, playing tricks on cognition, and even upping the odds of a deadly overdose. Below is a list of the potential impacts of polypharmacy on patients and healthcare overall.

• Adverse Drug Events: Every drug in a patient's regimen increases the risk of an adverse drug event by 7%-10%. This includes consideration of drug-to-drug interactions.
• Falls: Taking four or more drugs is associated with an 18% risk for falls and taking 10 or more drugs is associated with a 50% increased risk for falls.
• Cognitive Effects: Delirium is twice as likely in older patients who are taking 6 or more drugs than in those taking fewer medications. Older patients who take 10 or more drugs are 2.5 times more likely to have impaired cognition than those taking 5 or less.
• Overdose and Mortality: Older patients taking multiple medications have a greater chance of death than those taking no medications.
• Decreased Quality of Life: Patients on multiple medications are more likely to take on an illness identity, experience increased stress, and have worsening underlying mental health issues.
• Financial Strain: Polypharmacy can result in a 30% increase in medical costs to a patient due to increased co-pays, additional specialist visits, and more. 
• Effects on the Healthcare System: Polypharmacy can also negatively impact healthcare systems. Some of the consequences include decreased clinician functionality and productivity, an increased burden on the healthcare system, an increase in medication errors, and an increased cost of healthcare.

Understanding the root of polypharmacy is a multifaceted challenge. There are several risk factors that make it more likely that a patient is prescribed four or more medications:

• Multimorbidity is a major risk factor, especially when several subspecialists are involved, and a primary care clinician is not coordinating the care.
• Older age may necessitate multiple prescriptions, to appropriately manage multiple coexisting medical conditions. Such conditions may include decreased renal and hepatic function, lower lean body mass, low or high blood pressure, reduced hearing, vision, cognition, and mobility issues, diagnoses of cancer, low-income individuals, developmental disabilities, especially autism, severe mental health disorders, and substance abuse disorders, can cause the need for polypharmacy.
• Individuals using opioids are also more likely to have more comorbidities that are often psychiatric. There is also more risk for CNS polypharmacy and more risk for complications, such as QTC prolongation, which is an abnormal heart rhythm.
• Medication changes can occur during the hospitalization of a patient, as there often is little communication between the hospital team and the patient’s primary care clinician.
• Children may not be able to communicate the side effects of medications or how they respond to certain medications effectively.
• Automated refill systems may experience a lag between when an automated refill runs out and when the medication is changed or discontinued by the provider.

Polypharmacy is a looming crisis with far-reaching consequences and adverse effects, and the time to address it is now. By understanding the complexities and challenges it poses, and learning about the process of deprescribing, NPs and PAs in primary care can pave the way for a healthier, happier, and more medication-conscious future.

We’ve just skimmed the surface of polypharmacy in this overview. To learn more, enroll in Primary Care Bootcamp for NPs and PAs, an on-demand curriculum with over 40 courses that review topics and strategies to help APPs confidently and compassionately provide care.


Angela D'Antonio, NP is an ANCC-certified Family Nurse Practitioner with additional certification in addictions nursing. She holds a BA in psychology from Dartmouth College, and MSN from MGH-IHP. For over twenty years, she has dedicated her career to caring for the underserved homeless, incarcerated, and for the past six years at Tewksbury Hospital for DPH on a unit for patients with acute medical issues related to substance use disorder. Angela has two wonderful teenagers at home. In her spare time, she loves to hike, garden, bake, and cross-stitch.