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Research Highlights

The dangers of polypharmacy and the case for deprescribing in older adults

Medicines are meant to help, not harm. But sometimes taking too many drugs can be dangerous, especially for older adults.

The use of multiple drugs to treat diseases and other health conditions is known as polypharmacy. This is a growing concern for older adults. Polypharmacy is more common among older adults, many of whom have multiple chronic conditions (MCC), defined as two or more chronic conditions such as arthritis, asthma, chronic obstructive pulmonary disease, coronary heart disease, depression, diabetes, and hypertension. But taking too many drugs can lead to safety concerns. Read on to learn about NIA’s support for polypharmacy research and how our work in this area can help ensure older adults take only those medicines they need to help them live full, healthy lives.Older adult's hand pouring medications onto a table and adding them to a pillbox

Adults age 65 and older tend to take more medicines than any other age group because they may have several diseases or other health problems at the same time. Managing multiple medications can be expensive, difficult to track, and hard to manage, especially for those who are homebound or who live in rural areas. In addition, the use of many medications can increase the risk for adverse reactions (problems or side effects caused by a drug) and drug interactions (meaning two or more drugs don’t work well together, causing unintended problems).

According to a report by the Centers for Disease Control and Prevention, 83% of U.S. adults in their 60s and 70s had used at least one prescription drug in the previous 30 days and about one-third used five or more prescription drugs. The most commonly used drugs were cholesterol, high blood pressure, and diabetes medications.

Inappropriate polypharmacy — the use of excessive or unnecessary medications — increases the risk of adverse drug effects, including falls and cognitive impairment, harmful drug interactions, and drug-disease interactions, in which a medication prescribed to treat one condition worsens another or causes a new one. Patients may be prescribed medicines that are unlikely to help, potentially harmful, or misaligned with the person’s health goals. Polypharmacy also creates a tremendous burden for patients and their families, who need to understand the purpose of the many prescriptions written by multiple providers, get refills, take each medication at the correct time of day, and recognize side effects.

Researchers are studying deprescribing to reduce these risks and to improve outcomes in older adults with MCC. The goal is to reduce or stop medications that are potentially inappropriate or unnecessary, which can also make the management of medications less of a strain for patients and their families.

Scientists enter uncharted territory in the field of deprescribing

“A vast majority of health spending goes toward treating people with MCC, which includes about 75% of older adults,” said Marcel Salive, a health science administrator in NIA’s Division of Geriatrics and Clinical Gerontology. “Although most combinations of health conditions can be managed using typical approaches, complexity increases as the number of conditions increases. We are at the early stages of research into MCC and still grappling with how best to approach the problem so we can make progress in improving both treatment and quality of life.”

To shore up these efforts, NIA is developing a network of scientists working to advance the field of deprescribing. The U.S. Deprescribing Research Network, funded by NIA, aims to build an interdisciplinary community of researchers including physicians, pharmacists, nurses, and older adults and their care partners who are interested in improving research in the relatively new field of deprescribing. Its goal is to develop and share resources and support innovative pilot studies to improve the quality of care and health outcomes for older adults.

Deprescribing is an exciting and challenging field. There isn’t a one-size-fits-all approach. You must consider the potential risks and side effects, costs, and burden on the patient and caregiver, and balance these with the intended benefits.

— Michael Steinman, M.D., co-principal investigator of the network and associate director of the NIA-funded University of California, San Francisco Pepper Center for Aging Research

As noted by Cynthia Boyd, M.D., M.P.H., co-principal investigator of the network and professor of medicine at Johns Hopkins University, “The network is committed to fostering deprescribing research that addresses the important issues older adults and their care partners face when considering the potential benefits and harms of medications. Advances in deprescribing research will result from collaboration and diverse expertise.”

NIA-supported researchers are also conducting research on how deprescribing can help caregivers make decisions about palliative care for their loved ones with dementia. In other studies, they are testing deprescribing strategies for treating people with conditions such as Alzheimer’s disease or a related dementia, heart failure, and MCC.

Overcoming barriers to deprescribing among clinicians

In one NIA-funded pilot study, researchers are testing, in a real-world clinical practice, the effectiveness of an innovative protocol designed to overcome key barriers to deprescribing in patients with heart failure and improve patient-centered medication management. The study focuses on increasing patient confidence in decision-making about whether to continue or discontinue selected medications.

Heart failure with preserved ejection fraction (HFpEF) is a condition in which the left ventricle has become stiff and can’t fill with blood as it normally should. It is a leading cause of sickness and death and represents about 50% of heart failure cases. It is also the most common form of heart failure in older adults. Patients with HFpEF use a large number of medications, and some of these have questionable value and may even cause harm. The pilot study is a unique patient-centered approach for stopping potentially harmful medications in the HFpEF population.

“Despite its role as an integral part of patient-centric and goal-concordant prescribing practice, deprescribing is not frequently incorporated into routine clinical practice,” said Parag Goyal, M.D., M.Sc., director of the HFpEF and Cardiac Amyloidosis Programs at New York-Presbyterian/Weill Cornell Medicine. “We need to develop processes to overcome patient- and physician-based barriers that can lead to increased patient confidence in continuing or discontinuing medications.”

Assessing optimal medication management in Alzheimer’s disease and related dementias

The majority of people living with Alzheimer's and related dementias or mild cognitive impairment (MCI) typically have MCC. Living with these combinations of conditions can lead to more complex medication regimens for patients and is associated with a greater risk of adverse side effects and drug interactions, treatment burden, cognitive changes, and higher rates of hospitalization and mortality. Optimizing medication through deprescribing can help avoid adverse drug effects and improve outcomes for all patients with MCC, particularly for those who also have Alzheimer’s or a related dementia.

Older adult handing a prescription bottle to the pharmacistThe NIA-funded Optimize study tests a deprescribing intervention in a primary care setting for people with Alzheimer’s or a related dementia/MCC with the goal of placing participants on “just right” medication regimens. The study population includes older adults with these diseases who are on five or more medications, as well as their family caregivers. The goal is to refine and test a patient- and caregiver-centric deprescribing intervention that is applicable to multiple types of medications and can be adapted to a variety of health care delivery settings, including hospitals, doctor’s offices, long-term care facilities, pharmacies, and the home. The study also includes an intervention focused on increasing awareness among primary care providers about options and processes for deprescribing for people with Alzheimer’s or a related dementia/MCC and MCI. One aim is to test the effectiveness of the intervention in reducing the number of medications as well as secondary outcomes including patient falls, adverse drug events, hospital and skilled nursing facility utilization, effects on activities of daily living, and the amount of time individuals spend in outpatient office visits.

Initial findings indicate patients and family members are receptive to discussing discontinuing medications with their doctors and receiving educational materials about medications and deprescribing from their primary care clinician. In addition, while clinicians in the study were aware of the potential benefits of deprescribing, they indicated they would also benefit from suggested language to use for discussions with patients and families in different clinical situations.

“Most health care providers welcome discussions about medication necessity,” said Elizabeth A. Bayliss, M.D., M.S.P.H., senior investigator at the Institute for Health Research at Kaiser Permanente Colorado, who co-leads this study with Boyd. “Based on our experience with developing the Optimize study, we would encourage older adults to bring this topic up for discussion with their providers.”

Researchers are evaluating their findings to make evidence-based recommendations for deprescribing interventions.

“We have also been talking to clinicians about how to best incorporate deprescribing assistance into their clinical care streams, such as providing information to clinicians through periodic tip sheets,” said Bayliss. “These efforts could be evaluated to inform care or to inform new pragmatic [real-life] interventions.”

Making deprescribing part of patient-centered care

Another NIA-funded study builds on the Optimize study by testing a culturally competent intervention to help facilitate deprescribing discussions among clinicians, patients, and their care partners.

“Prescribing medications is often seen by clinicians as ‘doing something for the patient,’ while stopping medications is often seen as ‘giving up,’” said Ariel R. Green, M.D., Ph.D., M.P.H., assistant professor of medicine at the Johns Hopkins University School of Medicine.

Older couple video chatting with a doctor using a handheld deviceGreen’s research focuses on identifying how clinicians can best communicate with older adults and their care partners to increase acceptance of deprescribing. She also looks at developing and implementing pragmatic approaches to deprescribing in the complex primary care environment.

Green recently led a qualitative interview study with patients, care partners, and clinicians who participated in Bayliss’ and Boyd’s Optimize trial conducted by Bayliss and Johns Hopkins University’s Boyd.

“The Optimize trial is testing a ‘low-touch’ intervention that combines patient and family education about deprescribing with a clinician component designed to provide primary care providers with brief, practical deprescribing pearls of wisdom,” said Green.

Green’s interview study produced valuable insights about how best to align deprescribing in primary care with the priorities of patients and their families, including members of underrepresented minority groups. Key findings of the interviews included demonstrating the importance of linking deprescribing with patients’ and care partners’ overall goals of care, and framing deprescribing as routine and positive versus a withdrawal of treatment. Here too, physicians expressed the need for deprescribing communication tips addressing specific clinical situations.

Building on these studies, researchers completed a large national survey, funded by the U.S. Deprescribing Research Network, that explored the language and messaging older adults most responded to when receiving recommendations from their doctors to take fewer medications.

Researchers found that most older adults prioritized avoiding potential side effects over “feeling better now” and that this sentiment was associated with higher willingness to stop zolpidem (more commonly known by its brand name of Ambien), a sleep medicine that is considered potentially inappropriate for older adults because harms outweigh benefits.

“This finding suggests that linking deprescribing communication to maintaining overall health may be an effective strategy to engage patients,” said Green.

Building on what they learned from the Optimize trial, researchers will soon begin piloting Align: Aligning Medications With What Matters Most with funding from the NIA-funded IMPACT Collaboratory. In this study, a clinical pharmacist, working with a primary care provider, will conduct telehealth visits with people living with dementia, and their care partners, to align their medications with their overall goals of care. The pharmacist will then make concrete, actionable deprescribing recommendations to the primary care provider.

“The aim of all our research is to develop pragmatic interventions to improve communication between clinicians and older adults and their families about medication use so that prescribing is patient-centered, not purely disease-oriented and guideline-driven,” said Green. “We hope to foster a culture of thoughtful prescribing and deprescribing. That will require introducing patients and caregivers to the idea that deprescribing is possible and may help them feel better. Also, while medications can be helpful in many situations, they come with trade-offs that people need to be aware of.”

Examining polypharmacy risks in people with dementia

Memory problems, while common, are not the only symptoms of dementia. Behavioral and psychological symptoms, such as delusions, apathy, and agitation, are common at all stages of dementia and can cause significant distress for caregivers. As a result, people with Alzheimer’s and other forms of dementia often receive psychotropic or opioid medications such as sedatives, tranquilizers, and hypnotics for these and other symptoms such as depression, anxiety, and sleep problems. But combinations of three or more of these drugs can be dangerous and should be used with caution in people with Alzheimer’s.

In one NIA-funded study, researchers found that community-dwelling older adults living with dementia were prescribed psychotropic or opioid medications at rates that far exceeded use by older adults without dementia, despite the risk of serious side effects in people with dementia. In older adults, prescribing three or more of these types of drugs, called central nervous system (CNS)-active polypharmacy, may increase the risk of falls, overdoses, memory problems, and death.

The study is based on data from 1.2 million people with dementia and covered by Medicare. It focuses on medications such as antidepressants, sedatives used as sleep medications, opioid painkillers, antipsychotics, and anti-seizure medications.

Nearly 70% of the study population was prescribed at least one of these medications at least once during the study period in 2018. Nearly half of all the people with dementia took one or two of them for more than one month.

Most significantly, researchers found that 13.9% met the definition of CNS-active polypharmacy, having taken three or more of these drugs for more than one month. Many of these CNS-active medications can worsen cognition, obviously a concern for older adults with dementia. And specifically for opioids, there is an increased risk of respiratory suppression and death when combined with medications that can slow brain activity, including benzodiazepines, antipsychotics, and gabapentinoids. These drug-drug and drug-disease interaction risks may be even greater for older adults with dementia who also may have difficulty communicating any adverse effects.

“For medications with limited evidence of benefit — which I would argue is the case for many psychotropic medications prescribed to people living with dementia — older adults are then only left with the potential harms,” said Donovan Maust, M.D., associate director of the Geriatric Psychiatry Program at the University of Michigan School of Medicine, who led the study. “So if you can minimize their exposure to the medications, then you would reduce the risk of those harms, such as a fall and injury.”

Researchers are now looking at prescribing patterns to identify systems or clinicians who could benefit from provider education or processes to guide prescribing.

The ethics of deprescribing in dementia care

People with dementia and their caregivers are faced with significant care challenges. The aim of IN-PEACE (Indiana version of Palliative Excellence in Alzheimer Care Efforts) is to improve the care of adults in this community who are living with dementia, and their family caregivers, through an innovative model of supportive care. This care model combines an existing, evidence-based dementia care intervention with a new one for palliative care in dementia.Older adult with dementia and her family caregivers

One part of the intervention involves advance care planning and goals of care discussions; support for caregivers in making common decisions about dementia care; reducing burdensome treatments; and improving symptom management, including those of a neuropsychiatric nature. Researchers are conducting a related study to explore caregivers’ perspectives on the ethical considerations of deprescribing medications. They also want to learn how these caregivers prefer to communicate about these decisions, and what hinders or helps facilitate related conversations. More than 20 caregivers from the IN-PEACE study intervention arm were selected for one-time, in-person, or phone interviews with the study team.

“What we have been seeing regarding deprescribing in our semi-structured interviews of caregivers has been quite interesting and varied,” said Greg A. Sachs, M.D., co-director of the Research in Palliative and End-of-Life Communication and Training (RESPECT) Center at Indiana University, who leads the study.

According to Sachs, there are some caregivers who trust the physician caring for their family member with dementia and would be quite ready to discontinue medications based on that doctor’s recommendation. Other caregivers would have many questions about the rationale for stopping the medication and would want assurances that the physician would closely monitor their loved one to ensure symptoms don’t return, and the ability to restart the medication if needed.

Some caregivers saw deprescribing as something positive that could simplify the medication regimen and make their lives and the lives of the individual with dementia easier. Other caregivers, even some helping to manage multiple medications and complex regimens for the person with dementia, did not see medications as a burden and thus this was not a motivator for deprescribing.

“I am most interested in getting beyond lists of medications that older adults ought not be taking based on more purely medical and pharmacological considerations — what I would contend should be ‘low hanging fruit,’ — to tackle medications that used to be appropriate for patients but might no longer be so because of where the patient is in their life, illness trajectory (including remaining life expectancy), or goals of care,” said Sachs.

This gets into areas relating to ethics, palliative care, and communication. For example, Sachs described one scenario involving a patient enrolled in hospice who has a life expectancy of fewer than six months. The individual enters hospice while regularly taking a statin to lower cholesterol and prevent a heart attack, but this has no benefits to the patient’s overall comfort. With both a limited life expectancy and goals of care focusing on comfort, the statin would be a candidate for deprescribing.

According to Sachs, the hospice scenario is relatively straightforward because the goals are clear and lifetime remaining is brief. Moving “upstream” to where patients may have longer to live and may be more focused on treating their medical conditions makes deprescribing more challenging.

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