The problem with polypharmacy

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As the population ages and patients present with more complex health conditions, the phenomenon of polypharmacy - defined as the regular use of five or more medications by older adults ­- has become increasingly common.

A 2024 study published in JAMA Internal Medicine found that, in the United States, the number of older adults (65 and over) who take five or more medications had nearly doubled in 20 years, from 24% in 2000 to more than 40% in 2020. Approximately 35% of age 60-plus adults take five or more medications daily, according to Centers for Disease Control and Prevention data.

Polypharmacy can result in negative drug interactions and increase the chances of serious side effects. These issues are of particular concern for older adults, whose metabolisms tend to slow with age and who are at greater risk of adverse events due to medication side effects. Such events include falls, confusion, loss of alertness, and renal failure. Studies suggest that the risk of adverse events increases with each medication taken.

The period immediately after a hospitalization can be particularly risky. An estimated 20% of hospital readmissions, a key indicator of a breakdown in health care, can be attributed to adverse medication events.

Despite these concerns, experts say that the concept of "deprescribing," or weaning patients off drugs that may be unnecessary or harmful, is not a simple endeavor.

"Deprescribing is not just the mirror image of prescribing. It requires a different set of skills," says Michael Steinman, MD, a professor in the Division of Geriatrics at the University of California, San Francisco.

Researchers in the United States and Canada are studying the impacts of polypharmacy and best practices for deprescribing, but experts say that educating clinicians and incentivizing health systems to focus on deprescribing are key to addressing the problem.

Systemic barriers

In the United States, the Food and Drug Administration has approved more than 24,000 prescription drugs and adds nearly 50 new drugs each year. The side effects of these medications can vary significantly depending on the individual patient, what other medications and supplements they are taking, the dosing, and even the time of day they are taken, explains Demetra Antimisiaris, PharmD. Antimisiaris led the Jean Frazier Polypharmacy and Medication Management Program at the University of Louisville Schools of Medicine and Public Health and Information Sciences before her retirement last year.

Patients with complex conditions, especially older adults, often see multiple specialists or visit different hospitals or clinics that may not share electronic health records. This means that it's critical for a clinician to take the time to thoroughly review each medication the patient is taking regularly and when prescribing a new drug. Such a review can take up to an hour, Antimisiaris says. Most physicians spend an average of 15 minutes with each patient.

Furthermore, there are more financial incentives to prescribe new medications than there are to deprescribe, in part because pharmaceutical companies fund clinical trials that inform standards of care and because there are inadequate billing codes for medication management, Antimisiaris explains.

Often, pharmacists assume the responsibility of evaluating medications and help flag any major concerns. Medicare Part D covers an annual visit with a pharmacist to review medications and, for Medicare recipients who live in nursing homes, pharmacist medication reviews are required monthly. Nurses in hospitals and doctors' offices can also play an important role in ensuring that patients take their medications appropriately.

"Polypharmacy is a team sport," Antimisiaris says. "There's no way one provider can manage it all."

Even with multiple clinicians involved, deprescribing is complex.

"It is very easy to start people - especially older adults - on medication. It's not easy to stop them," Steinman says.

In 2019 the National Institute on Aging funded the U.S. Deprescribing Research Network, following in the footsteps of Canada and other countries that were reevaluating their medication use. Before then, relatively little research had been done on how to effectively deprescribe and assess the clinical outcomes of stopping medications, says Steinman, the network's coprincipal investigator.

Since its inception, the network has funded early-career investigators to support their research and has worked to disseminate the latest findings to health care systems, caregivers, and patients.

In many cases, health system efforts have increased awareness, including the use of algorithms built into electronic health records that signal to a provider when a medication may be contraindicated. And the most progress has been achieved with deprescribing classes of medications that are broadly known to be more harmful and addictive, such as opioids and benzodiazepines, Steinman adds.

While polypharmacy most often affects older adults, children and middle-aged adults are increasingly being treated for complex chronic conditions requiring multiple medications. Clinicians and researchers will have to monitor how those medications over long periods of time impact their patients of all ages, Antimisiaris notes.

"One of the major challenges is that a lot of deprescribing is individualized," Steinman says. "For one person a medication might be appropriate and [for] another, inappropriate. It's often hard to make a rule that can be operationalized."

That's where education comes in, according to Antimisiaris, who is currently writing a polypharmacy textbook, scheduled to be published by Elsevier in October.

"It's no longer enough to just learn the mechanisms of how the [medications] work. Students need to learn how to manage them," she says. "It might be wise to integrate polypharmacy as a thread throughout problem-based learning."

In Canada, experts have been working on deprescribing for about a decade. The Canadian Medication Appropriateness and Deprescribing Network was established in 2016 and started by forming committees to take a multipronged approach, including educating health care providers and increasing public awareness, explains Emily McDonald, MD, an associate professor at McGill University in Montreal and the network's director.

In 2023, the network created a curricular framework to encourage medical schools and other health professions schools to engage students with the concepts of polypharmacy and deprescribing early in their education. McDonald says she's seen a culture change in recent years.

"Ten years ago, when I was first starting on faculty, I was trying to convince people to deprescribe sleeping pills for older adults," she says. "Now I review [medication lists] with students and residents, and they bring it up on their own."

McDonald says that the network will be working intensively this year to coach faculty on how to integrate deprescribing into the curricula.

Increasing public awareness

But even with increased clinician education and awareness of polypharmacy's dangers, the role of the patient and caregivers remains paramount. Antimisiaris says that educating the public to be mindful of their own medication management is just as important.

"As physicians, it's kind of scary when patients can't name their drugs and when people can't name any side effects. That means they can't monitor themselves for side effects," she says.

She advises people who are taking multiple medications, or their caregivers, to keep an up-to-date and detailed list of all medications and supplements they are taking, and to track any side effects, noting when they start, and to be conscious of timing, dosing, and any other instructions for how the drugs should be taken. Additionally, she recommends checking new medications for adverse interactions using a free online drug interaction tracker, such as the one provided by WebMD.

Even beyond adverse events, Antimisiaris notes that the patient's preferences should matter when it comes to prescribing and deprescribing. If a medication is helpful in one way but negatively impacts the person's life, such as causing them to have to use the bathroom often or limiting their mobility, that matters when it comes to optimizing the use of medications.

"There's been an organic interest in polypharmacy from the public - [from] people who had horrendous experiences," Antimisiaris says. "Making the public more medication literate is the mission."