Polypharmacy in Older Adults: A Comprehensive Overview

This research document provides a comprehensive overview of polypharmacy in the older adult population. It covers the definition and prevalence of polypharmacy, common medication-related problems including the psychological burden and prescribing cascades, the underlying physiological and systemic reasons for its high prevalence, effective methods to reduce medication-related harm with a focus on deprescribing and non-pharmacological alternatives, and critical red flags that signal the need for an urgent medication review.

Defining and Quantifying Polypharmacy

Polypharmacy is most commonly defined as the concurrent use of five or more medications [1][2][3] . This definition can also include over-the-counter (OTC) medications and supplements [4] . Beyond a simple numerical count, a qualitative definition of polypharmacy includes the use of any medication that is unnecessary, ineffective, or potentially harmful [5][6][7][8] . While using multiple medications can be appropriate for managing multiple chronic conditions (multimorbidity), it becomes problematic when it leads to negative health outcomes [1][9] .

Recent statistics highlight the significant and growing prevalence of polypharmacy, which increases with age and the level of care required [1] .

• Global Prevalence: A large-scale meta-analysis from August 2024 found the overall global prevalence of polypharmacy in older adults to be 39.1% . The same study found that 13.3% experienced "hyperpolypharmacy," defined as taking 10 or more medications [10] .
• Prevalence by Age: Data from the Survey of Health, Ageing and Retirement in Europe (SHARE) shows a clear trend of increasing polypharmacy with age :
  • 65–74 years: 30.0%
  • 75–84 years: 41.1%
  • 85 years and older: 49.4%
• Prevalence by Healthcare Setting: The environment where an older adult receives care is a major determinant of polypharmacy rates [1] .
  • Community/Outpatient: Prevalence in community-dwelling older adults ranges from 19.1% to 59% [1][11][12] . In the United States, prevalence in this group increased from 23.5% to 44.1% between 1999 and 2018 [13] .
  • Hospitals: Hospitalized older adults show significantly higher rates, with studies reporting prevalence from 46% to as high as 91.8% [1][12][4] . Hospitalization itself often increases the number of prescribed medications [4] .
  • Long-Term Care Facilities (LTCFs): This setting has the highest rates [13] . Studies report that up to 91.2% of nursing home residents experience polypharmacy, with as many as 65% taking ten or more medications [12][14][15][16][17][5] .

Common Medication-Related Problems

The use of multiple medications in older adults is associated with a host of problems, which can significantly impact an individual's quality of life and lead to increased healthcare utilization, hospitalizations, and even death [1][11][8] .

Key problems include:

• Adverse Drug Events (ADEs): These are injuries resulting from medication use and are a leading cause of emergency department visits and hospitalizations in older adults [1][18] . Common ADEs are linked to anticoagulants, hypoglycemics, cardiovascular drugs, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs).
• Drug-Drug Interactions: The risk of interactions between different medications increases exponentially with the number of drugs taken [15][19] . These interactions can diminish a medication's effectiveness or amplify its effects, leading to toxicity.
• Increased Risk of Falls and Fractures: Certain medications, particularly those affecting the central nervous system like sedatives, opioids, and antidepressants, can cause dizziness, drowsiness, and impaired balance, significantly increasing the risk of falls [1][20][15][16][21][22] .
• Cognitive Impairment: Polypharmacy, especially the use of psychotropic and anticholinergic drugs, has been linked to cognitive issues ranging from confusion and memory problems to an increased risk of delirium and dementia [1][16][23][6][21][24][25][26] .
• Medication Non-Adherence: Complex medication regimens can be confusing and overwhelming, leading to unintentional errors such as missing doses, taking incorrect amounts, or stopping a medication altogether [27][28] .
• Increased Hospitalizations and Healthcare Costs: The complications arising from polypharmacy, including ADEs and falls, contribute to a higher rate of hospital admissions, longer hospital stays, and increased overall healthcare expenditures [1][7][29][30] .

In-Depth Focus: The Psychological and Emotional Burden

Beyond the physical risks, managing a complex medication regimen imposes a significant psychological and emotional burden on both older adults and their informal caregivers [2] .

• For Older Adults: The daily task of managing numerous prescriptions can be overwhelming, leading to confusion, anxiety, and depression [1][11][31][32] . The sheer number of pills can serve as a constant, unwelcome reminder of chronic health conditions, negatively impacting self-perception and quality of life [33] . The fear of making errors, experiencing side effects, and the financial strain of multiple prescriptions further compound this emotional toll [11][31] .
• For Informal Caregivers: Caregivers, often family members with little or no formal training, bear a heavy responsibility for medication management, which is a major source of stress, frustration, and anxiety [11][10][34] . This all-consuming task can contribute to caregiver burnout, depression, and a decline in their own health [35] . Research has even shown that the stress of caregiving can lead to an increased use of anti-anxiety medications among caregivers themselves [36] .

In-Depth Focus: Prescribing Cascades

A prescribing cascade is a dangerous and often overlooked phenomenon where an adverse drug event is misinterpreted as a new medical condition, prompting the prescription of another drug to treat it [1][5][6][37] . This can create a domino effect of escalating and unnecessary medication use, leading to polypharmacy and significant harm [7][8] .

Common and Clinically Significant Prescribing Cascades [21][24] :

In-Depth Focus: Functional Decline and Frailty

Beyond discrete ADEs, polypharmacy contributes to functional decline and frailty through more insidious mechanisms [43] . There is a bidirectional relationship: frailty often leads to more prescriptions, and polypharmacy itself can accelerate the development of frailty [19][44] . A high score on the Drug Burden Index (DBI), which measures cumulative sedative and anticholinergic exposure, is associated with impaired physical function and frailty [2][45][46][26][18] .

• Alteration of Homeostasis: Age-related changes diminish the body's physiological reserves and ability to maintain equilibrium (homeostasis) [10][47] . Multiple medications can stress these compromised systems, exhausting the individual's reserves and pushing them into a state of frailty, characterized by weakness, low endurance, and vulnerability [10][43] .
• Cumulative Effects: The cumulative anticholinergic and sedative burden from multiple drugs can directly cause cognitive impairment, confusion, dizziness, and falls, all of which are hallmarks of functional decline [15][16][19] .
• Impact on Nutrition and Physical Function: Side effects like sedation, appetite loss, or nausea can lead to poor nutritional status and reduced physical activity [47] . This directly impacts muscle mass and strength, accelerating the progression toward sarcopenia and frailty [47][44] .
• Cognitive and Psychological Burden: The sheer complexity of managing multiple medications can be confusing and stressful, leading to non-adherence, anxiety, and depression [10][16][27][28] . This psychological strain diminishes well-being and functional capacity [16][48][28] . Studies show that taking five or more medications is associated with a higher likelihood of functional decline, especially in those with dementia [48][23][46] .

Reasons for Polypharmacy: Systemic and Physiological Factors

Several interconnected factors contribute to the high rate of polypharmacy and the heightened risk of medication harm in older adults.

System-Level and Structural Factors

• Fragmented Care: Older adults with multimorbidity often see numerous specialists in a "siloed" approach [1][11][35] . This lack of care coordination means providers may prescribe without a holistic view of the patient's full regimen, increasing the number of drugs and risk of interactions [1][33][10] . Visiting multiple clinics is directly correlated with a higher number of prescribed medications [1][12] .
• Inadequate Communication: Poor communication about medications between healthcare settings (e.g., primary care and hospitals) is a major cause of errors [39][14][40] . Incomplete medication lists in referral letters and flawed medication reconciliation during care transitions are common and potentially harmful problems [39][14][41][29] . In long-term care, communication with off-site physicians often occurs by phone, a process that tends to result in adding, rather than removing, medications [36] .
• System-Level Incentives and Practices: Several systemic factors promote over-prescribing [35][45] . These include:
  • Prescribing to meet single-disease quality metrics without considering the whole patient [1][9][49] .
  • The use of automated prescription refill services [1][45] .
  • Payment systems that reward more services rather than medication optimization or deprescribing [20] .
• Provider and Guideline Factors: Physicians often have limited time during visits for thorough medication reviews [4] . Furthermore, clinical practice guidelines are frequently focused on single diseases and fail to address the complexities of multimorbidity in older adults, leading to a high medication burden when multiple guidelines are followed [9][49] .

Increased Susceptibility: Age-Related Physiological Changes

Older adults are more vulnerable to medication-related harm due to predictable physiological changes that alter how their bodies process (pharmacokinetics) and respond to (pharmacodynamics) drugs [33][39][14][2] .

Pharmacokinetic Changes (What the Body Does to the Drug)
These changes often lead to higher drug concentrations and prolonged drug effects [33][39] .

• Metabolism (Liver Function): With age, both liver mass and blood flow to the liver decrease by about 1% per year after age 40 [1][40] . This reduces the "first-pass effect," leading to higher circulating concentrations of certain drugs [1][41] . The function of key liver enzymes (Phase I cytochrome P-450 system) can decline, reducing drug clearance by 30% to 40% for some medications [40][1][48] .
• Excretion (Kidney Function): This is one of the most significant changes [1] . The glomerular filtration rate (GFR) declines by an average of 8 mL/min/1.73 m² per decade after age 40 [1][48] . This prolongs the half-life of drugs cleared by the kidneys, leading to accumulation and toxicity if doses are not adjusted [12][23][50] . Critically, serum creatinine levels may remain in the normal range despite reduced kidney function due to lower muscle mass, potentially masking the need for dose adjustments [1][11] .
• Distribution (Body Composition): Body composition changes with age, with an increase in body fat and a decrease in total body water and lean mass [1][48][23][17] .
  • The increased fat expands the volume of distribution for fat-soluble (lipophilic) drugs like diazepam, prolonging their elimination half-lives and increasing the risk of accumulation [1][40][51] .
  • The reduced body water decreases the volume of distribution for water-soluble (hydrophilic) drugs, potentially leading to higher initial drug concentrations [1][11][51] .

Pharmacodynamic Changes (What the Drug Does to the Body)
Older adults often have an increased sensitivity to medications, meaning a standard dose can produce a much stronger effect or more side effects [14][16][5] .

• Increased Sensitivity: There is often an exaggerated response to several classes of drugs, including anticoagulants, cardiovascular agents, and psychotropics [10][14][5] . The central nervous system is particularly vulnerable, leading to increased sensitivity to the sedative and cognitive effects of benzodiazepines and opioids [20][51] .
• Reduced Homeostatic Reserve: The body's ability to maintain equilibrium (homeostasis) diminishes with age [14][15] . This makes it harder for an older person's body to compensate for the physiological stress caused by a medication, such as a drop in blood pressure from an antihypertensive, increasing the risk of adverse events like orthostatic hypotension and falls [20][16] .

Methods to Reduce Medication Harm

Addressing the challenges of polypharmacy requires a proactive, collaborative, and patient-centered approach focused on optimizing medication regimens and preventing harm [16][43] .

• Maintain a High Index of Suspicion: When an older adult presents with a new symptom, the first question should always be whether it could be an adverse drug reaction [1][11][3] . This is especially critical if a new medication was recently started or a dose was changed [4][7] .
• Conduct Comprehensive Medication Reviews: A systematic assessment of all medications a patient is taking—including prescription, OTC, and supplements—is essential to identify and resolve medication-related problems [40][4][16][50] .
• Medication Reconciliation: This process involves creating the most accurate list possible of all medications a patient is taking and comparing it against physician's orders at every transition in care (e.g., hospital admission, discharge) to prevent errors [41][7] .
• Start Low and Go Slow: When initiating a new medication in an older adult, it is crucial to start with the lowest effective dose and increase it gradually to minimize the risk of side effects [39][4][22] .

In-Depth Focus: Non-Pharmacological Alternatives

Before prescribing, and as part of deprescribing, providers should explore evidence-based non-drug interventions, which can be safer and more effective for common conditions that contribute to polypharmacy .

• For Chronic Pain: A growing body of evidence supports non-drug therapies to reduce pain, improve function, and decrease the need for pain medications [31][34] .
  • Physical and Mind-Body Therapies: Physical therapy, tai chi, yoga, walking, acupuncture, and massage therapy are all recognized as beneficial for managing chronic pain [20][13][4][15][2][3][32][35][9][19][26][18] .
  • Psychological Approaches: Cognitive Behavioral Therapy (CBT) and mindfulness-based interventions help patients change negative thought patterns and emotional responses to pain, improving coping skills [1][49][37][45][46][28] .
• For Insomnia: Cognitive Behavioral Therapy for Insomnia (CBT-I) is considered the first-line, gold-standard treatment for chronic insomnia, with longer-lasting effects than medication [16][43][47][2][34][49][37][19] . Key components include:
  • Sleep Hygiene Education: Implementing habits conducive to good sleep, like maintaining a regular schedule and creating a restful environment [47][2][45][46] .
  • Stimulus Control: Re-associating the bed with sleep by only going to bed when sleepy and leaving the bedroom if unable to sleep [34][29] .
  • Sleep Restriction: Limiting time in bed to more closely match actual sleep time to improve sleep efficiency [2][34] .
  • Other Interventions: Physical exercise, music therapy, light therapy, and mindfulness are also effective strategies [16][48][23][31][36] .

In-Depth Focus: Deprescribing

Deprescribing is the planned and supervised process of dose reduction or discontinuation of medications that may be causing more harm than benefit [1][13][47][5][6][7][36] . When a prescribing cascade is identified, the first step should be to consider if the initial drug can be stopped, substituted, or have its dose reduced [1][8] .

Frameworks and Identifying Patients
A widely cited framework for deprescribing involves a systematic five-step process [4][8] :

1. Medication Review: Ascertain a comprehensive medication history and the indication for each drug.
2. Risk Assessment: Evaluate the patient's overall risk of medication-related harm.
3. Benefit vs. Harm Analysis: For each medication, weigh its benefits against its potential harms in the context of the patient's goals, life expectancy, and preferences [50] .
4. Prioritization: Prioritize medications for discontinuation that have the least favorable benefit-to-risk ratio.
5. Implementation and Monitoring: Create a tapering plan and monitor the patient closely for withdrawal symptoms, return of the underlying condition, and any improvements [52] .

Patients who are strong candidates for deprescribing include those with:

• Frailty, cognitive impairment, or functional decline [41][16][43][21] .
• A life-limiting illness or limited life expectancy [16][47][24][25] .
• A recent adverse drug event, such as a fall or new confusion [15][24] .
• A patient's expressed desire to reduce their medication burden [1][51][25] .

Utilizing Clinical Tools and Interprofessional Care

• Evidence-Based Screening Tools: Clinicians use explicit, criterion-based tools to systematically identify potentially inappropriate medications (PIMs) [50][51] .
  • AGS Beers Criteria®: Provides lists of PIMs that are typically best avoided in older adults in general and in those with specific diseases or syndromes, with the goal of reducing ADEs [41][18] .
  • STOPP/START Criteria: The STOPP (Screening Tool of Older People’s Prescriptions) and START (Screening Tool to Alert to Right Treatment) criteria are often used together [52] . STOPP helps identify PIMs, while START helps identify potential prescribing omissions, prompting clinicians to initiate beneficial therapies that may be missing [30][9][53] .
• Quantifying Cumulative Medication Burden: ACB and DBI: To assess risk more precisely, clinicians use validated scales to quantify the cumulative sedative and anticholinergic load from a patient's regimen [50][51][17] .
  • Anticholinergic Burden Scale (ACB): This widely used scale ranks drugs on a scale of 0 to 3 based on their anticholinergic potential [34][52] . A high total score is strongly associated with adverse outcomes, including cognitive decline, dementia, falls, fractures, and all-cause mortality [5][6][8][21][24][25][22][38][29][9][30] . A score of 3 or more is a common threshold that prompts an urgent medication review [5][42][30] .
  • Drug Burden Index (DBI): This tool measures the cumulative exposure to both anticholinergic and sedative drugs, incorporating the dose [31][35][18] . A high DBI score is predictive of impaired physical and cognitive function, frailty, falls, mortality, and emergency department visits [2][45][46][26][18] .
  • Guiding Deprescribing: These scores are instrumental in identifying high-risk patients and guiding deprescribing decisions [51][17][31][9] . They provide an objective framework for discussing risks and benefits with patients and caregivers [51][54][3][2] . Some health systems are integrating these tools into electronic health records for real-time decision support [31][45] .
• Interprofessional Collaboration and MTM: A team-based approach involving physicians, pharmacists, nurses, and other providers is crucial [16][22][38][42][3][32] .
  • Medication Therapy Management (MTM): This is a patient-centric service led by pharmacists to optimize medication use [7][8][54][49] . It involves comprehensive medication reviews, personalized action plans, and patient education [7][8][21][55][56] .
  • Proven Effectiveness of MTM: Pharmacist-led MTM has been shown to reduce hospital visits and readmissions, improve medication adherence, and improve clinical outcomes for chronic diseases [7][8][24][55] . It is also cost-effective, with some analyses showing a return on investment of $2.30 for every dollar spent [7][21][25][54][34] .

Special Considerations: Long-Term Care (LTC) Facilities

LTC facilities present a high-risk environment for medication-related harm due to the residents' vulnerability and the setting's inherent complexities [5][29] .

Unique Challenges in LTC

• Vulnerable Population: Residents often have cognitive impairments and are unable to advocate for themselves, making them highly susceptible to medication errors [54][2] .
• High Prevalence of PIMs: Residents in LTC homes experience polypharmacy and are prescribed PIMs at higher rates than their community-dwelling counterparts [17][5] .
• Communication and System Gaps: Medical care is often provided by off-site physicians with limited knowledge of the residents, leading to communication breakdowns with on-site staff [41][3][36] . Facilities may lack integrated health IT, and high workloads and inadequate staffing can increase error risk [41][5][2][29][27] .
• Barriers to Deprescribing: There can be significant resistance to deprescribing from residents, families, or staff due to fear, a belief that a medication is still necessary, or a perception that it is a withdrawal of care [6][3][31][45][36] .

Evidence-Based Interventions in LTC

• Systematic Deprescribing: The primary intervention is the systematic implementation of deprescribing, guided by established algorithms and guidelines for specific drug classes like proton pump inhibitors (PPIs) [6][31][57] . This should be an individualized process involving slow tapers [36] .
• Pharmacist-Led and Interprofessional Reviews: Expanding the role of pharmacists to conduct regular, on-site medication reviews and work collaboratively with the care team is a key enabler of successful deprescribing [3][32]. Multifaceted models that give greater professional autonomy to pharmacists and nurses have been shown to significantly reduce polypharmacy and PIMs [58][59] .
• Education and Shared Decision-Making: Educating healthcare professionals, residents, and families about the goals of deprescribing and the risks of polypharmacy can help overcome resistance and ensure care aligns with the resident's goals [5][3] .
• Technology and Decision Support: Electronic decision support tools can be highly effective. One study using the MedSafer tool to generate individualized deprescribing reports saw a 23.7% increase in deprescribing [45] . Smart medication dispensers can also improve adherence and reduce administration errors by staff [34][37] .

Empowering Patients and Caregivers

Patients and their caregivers are vital partners in preventing the harms of polypharmacy . Empowerment comes from knowledge, organization, and effective communication [8] .

Actionable Strategies for Medication Management:

• Maintain a Comprehensive Medication List: Keep an up-to-date list of all prescription medications, OTC drugs, vitamins, and herbal supplements, including the dose and reason for taking each one [43][48][29] . Bring this list to every medical appointment [9] .
• Use One Pharmacy: When possible, use a single pharmacy to fill all prescriptions . This allows the pharmacist to have a complete record and better screen for potential interactions and problems [49] .
• Report New Symptoms Promptly: If you experience any new health problems after starting a new medication, contact your doctor immediately . Do not assume it is a new illness [4][2] .

Utilizing Medication Adherence Tools:

• Pill Organizers: These simple tools can reduce confusion and improve adherence [12][39] . However, a transition to a pill organizer should be guided by a doctor or pharmacist, as research shows it can sometimes lead to problems like falls or hypoglycemia by ensuring patients take the full dose of medications they were previously under-dosing [2][29] .
• Automated Dispensers: These devices dispense medications at pre-programmed times with alarms, which can reduce caregiver stress and improve safety, especially for those with cognitive impairments [14][34][9][49][37][45]. However, usability varies, and some models can be complex to set up and refill [40][41][31][19] .
• Digital Apps and Platforms: Smartphone apps (e.g., Medisafe) can improve adherence with reminders and educational content [1][12][39][3][44][46] . However, usability for older adults can be a concern due to issues like difficult navigation or poor visibility [27] .

Effective Communication with Healthcare Providers:

• Prepare for Appointments: Before a visit, write down questions, new symptoms, and concerns to discuss [48][42].
• Ask Probing Questions: When a new medication is prescribed, ask: "Why do I need this medication?", "What are the potential side effects?", and crucially, "Could this new symptom be a side effect of a medication I'm already taking?" [49] .
• Discuss Deprescribing: It is appropriate to ask, "Are all of these medications still necessary?" or "Could we review my medications to see if any can be stopped or reduced?" [17] .

Red Flags Requiring Urgent Medication Review

Certain signs and symptoms in an older adult on multiple medications should be considered "red flags" that warrant an immediate and thorough medication review to prevent serious harm.

Urgent review is necessary in the following situations:

• Recent Falls or Dizziness: Any new onset of falls, dizziness, or balance problems should trigger an immediate evaluation of the medication list [24][44] .
• Sudden Changes in Cognitive Function: The appearance of confusion, delirium, or a sudden decline in memory or alertness is a significant red flag for a potential ADE [24][26] .
• New or Worsening Symptoms: Any new symptom that appears after starting a new medication or changing a dose should be considered a potential side effect until proven otherwise. This is crucial to prevent a prescribing cascade [15][25][2] .
• High-Risk Medications or Burden Scores: The use of medications with a high risk of adverse effects (e.g., anticoagulants, insulin, opioids, benzodiazepines) or the presence of a high cumulative burden score from tools like the ACB or DBI should prompt careful review [41][15][5][42][30] .
• Significant Changes in Health Status: Events such as a recent hospitalization, a new diagnosis, or a decline in kidney or liver function necessitate a review of all medications to ensure they are still appropriate and safely dosed [1][48] .
• Patient or Caregiver Concerns: Any concerns expressed by the patient or their family about side effects, the psychological burden of the regimen, or its complexity should be taken seriously and addressed promptly [1][25][42] .

Executive Summary

Polypharmacy, the use of five or more medications, is a prevalent and growing concern in the older adult population, with global prevalence at 39.1% and rates approaching 50% in those over 85 [10][1] . It is driven by multimorbidity but is exacerbated by systemic healthcare issues like fragmented care, inadequate communication, and single-disease clinical guidelines [1][39][35][9] . The risks are amplified by predictable age-related physiological changes that alter drug metabolism and increase sensitivity to drug effects [1][48][5][2] . This elevates the risk of adverse drug events, falls, functional decline, and the prescribing cascade, where a drug side effect is mistaken for a new condition [1][6][44] . Furthermore, complex regimens impose a significant psychological and emotional burden on both patients and their caregivers, leading to anxiety, depression, and burnout [11][33][31][34] .

To mitigate these risks, a multi-pronged, patient-centered approach is essential. Key strategies include regular comprehensive medication reviews and maintaining a high index of suspicion for adverse drug events [1][50] . A cornerstone of management is deprescribing—the planned discontinuation of medications causing more harm than benefit—guided by evidence-based clinical tools [13][7] . Clinicians can use screening tools like the AGS Beers Criteria® and STOPP/START criteria, as well as quantitative scales like the Anticholinergic Burden Scale (ACB) and Drug Burden Index (DBI), to identify high-risk patients and guide deprescribing decisions [50][31][18][52] . Exploring non-pharmacological alternatives for conditions like chronic pain and insomnia is crucial to reduce medication load [16][31] . Interprofessional care models, particularly pharmacist-led Medication Therapy Management (MTM), have proven highly effective at improving outcomes [7][24][55] . Finally, empowering patients with knowledge and tools, and remaining vigilant for "red flags" like recent falls or sudden cognitive changes, are vital for ensuring medication safety [8][24][2] .