Polypharmacy is defined as the regular use of five or more medications. While medication has become a central component of chronic disease management, polypharmacy raises important questions about overtreatment and patient safety. For many patients, particularly older adults managing multiple chronic conditions, polypharmacy may be necessary. However, the cumulative burden of multiple medications can introduce significant health risks, including adverse drug interactions, medication non-adherence, functional decline and increased healthcare costs. As the U.S. healthcare system increasingly emphasizes medication-based interventions, understanding the scope and implications of polypharmacy is essential for balancing therapeutic benefit with potential harm.
Polypharmacy is associated with a 16% higher risk of hospitalization and a 25% higher mortality risk compared to those with one or two prescribed medications, outcomes that reflect both the complexity of underlying health conditions and the potential for medication-related complications.1 Beyond these clinical risks, polypharmacy contributes to substantial healthcare expenditures. Patients taking multiple medications face higher out-of-pocket (OOP) costs and greater likelihood of emergency department visits related to adverse drug events.
Growth in polypharmacy reflects several converging trends in healthcare. Clinical guidelines increasingly recommend multi-drug regimens to manage prevalent chronic conditions such as diabetes, hypertension and cardiovascular disease. Additionally, the aging U.S. population is living longer with multiple comorbidities, necessitating more complex pharmaceutical management. Notably, the growing recognition and treatment of mental health conditions has led to wider use of psychotropic medications across age groups.2 Also, direct-to-consumer (DTC) prescribing has increased access to prescription medications.3 Lastly, the proliferation of prescription medications will gradually imperil procedure-based medical interventions.
Managed holistically, polypharmacy can be clinically appropriate, but concerns persist about inappropriate prescribing, including the use of medications with limited benefit, duplication of therapeutic classes and continuation of drugs beyond their clinical utility.4 These patterns are particularly pronounced in older adults, who are more vulnerable to drug-drug interactions and age-related changes in drug metabolism. Notably, researchers found that over 34% of older adults taking five or more medications were using at least one potentially inappropriate medication.5
Understanding which patient populations are most affected by polypharmacy and which medication combinations are most prevalent provides insight into prescribing patterns and the health status of the population, along with identifying opportunities for intervention and de-prescribing. This analysis examines the demographic characteristics of polypharmacy patients and the most common drug combinations.
National all-payer claims data were used to examine polypharmacy prevalence and patterns from 2021 to 2024. Polypharmacy was defined as patients prescribed five or more medications from at least five unique drug classes during the study period. Drug classes that target acute conditions (e.g., antibiotics) were excluded from the analysis. Patient demographics were analyzed by age group (0-17, 18-44, 45-64 and 65 years and older) and gender (male and female). To identify the most common medication regimens, the analysis examined the most common therapeutic classes among polypharmacy patients.
In 2024, 50.9% of adults ages 65 years and older were prescribed five or more medications, followed by 38.0% of adults ages 45-64 (Figure 1). Patients under age 18 had the lowest share of polypharmacy at 12.0%, followed by adults ages 18-44 at 23.1%.
Polypharmacy prevalence increases substantially with age and varies by gender. Among the 65 and older population, polypharmacy rates increased from 47.7% in 2021 to 50.9% in 2024, with men and women experiencing nearly identical prevalence throughout the period (Figure 2). In the 45-64 age group, polypharmacy rates grew from 32.9% to 35.9% among men and from 36.2% to 39.7% among women. Polypharmacy rates in the 18-44 age group grew more slowly, increasing from 16.4% to 18.0% for men and from 25.1% to 26.1% for women. Gender differences were most pronounced in the 18-44 and 45-64 age groups, where women experienced polypharmacy at rates 8.1 and 3.8 percentage points higher than men in 2024, respectively. The under-18 population maintained the lowest and most stable polypharmacy rates, with 11.8% of boys and 12.1% of girls prescribed five or more medications in 2024.
Among individuals under age 18, ADHD medications appeared as a distinctive drug class. For women ages 18-44, antidepressants overtook contraceptives beginning in 2023 as the top-ranked class. Thyroid medications are a prominent drug class for women over age 45. Among men ages 18-44, antidepressants ranked as the highest therapeutic class, while for men ages 45-64, antidepressants rose from fourth to second place over the study period, suggesting growing mental health treatment utilization across male age cohorts.
The prevalence of polypharmacy across the U.S. population reflects both ongoing therapeutic innovation and the limitations of the U.S. healthcare system, which often defaults to pharmaceutical interventions, often for clinical conditions attributable in part or in whole to poor lifestyle decisions. For many patients, particularly those managing multiple chronic conditions, the concurrent use of multiple medications is potentially medically necessary and may improve quality of life. However, the data also reveal a healthcare system that may rely too heavily on medication therapy without sufficient attention to non-pharmacologic interventions or the cumulative risks of complex, and often fragmented, drug regimens.
The concentration of polypharmacy among older adults is especially concerning, given this population's heightened vulnerability to adverse drug events, cognitive impairment and functional decline associated with medication burden. As individuals age and often become more medically complex, prescriptions are often added incrementally, sometimes by multiple disconnected providers across different care settings, without a systematic review of whether existing medications remain necessary or beneficial. This prescribing cascade can result in patients taking medications to treat the side effects of other medications, further compounding complexity and risk. While polypharmacy is more common among older adults, one in ten children was found to be prescribed medications across at least five classes. Additionally, the higher share of women with polypharmacy among adults ages 18-64 may reflect differences in care-seeking behavior between men and women, which could influence time to treatment and overall health outcomes for men and women.
Polypharmacy represents not only clinical challenges, but also economic ones. Medication costs are the fastest growing segment across total healthcare spending, with retail prescriptions alone accounting for 9.2% of the $4.9T U.S. healthcare spending in 2023.6 In parallel, patients face expanding OOP liability for prescription drugs, contributing to medication non-adherence and financial strain. The downstream consequences of non-adherence, such as avoidable disease progression and preventable complications, can ultimately generate far greater costs than the medications themselves.
Polypharmacy trends also invite questions about financial incentives embedded within the healthcare system. Pharmaceutical representatives frequently engage with healthcare providers to promote new medications, offering samples, educational materials and other inducements that can influence prescribing behavior. While these interactions are ostensibly educational, they create subtle pressures that may prioritize newer, more expensive branded medications over older generic alternatives or non-pharmacologic approaches. Fee-for-service reimbursement models further reinforce this pattern by compensating providers for visits and prescriptions written rather than for outcomes achieved or medications deprescribed. These structural incentives can make it easier for clinicians to add a medication than to eliminate one, particularly when prescribing decisions occur across fragmented care settings with limited coordination.
Addressing polypharmacy utilization and appropriateness requires clinicians to adopt a more deliberate stance toward prescribing, regularly reassessing the ongoing appropriateness of each medication and engaging patients in shared decision-making about treatment goals and risk factors. Health systems should implement medication reconciliation protocols and clinical decision support tools that prioritize medication safety and quality over quantity. Payers can support these efforts through reimbursement models that reward comprehensive medication management rather than volume of prescriptions filled. Similarly, payers can provide greater transparency and create stronger incentives to use generic drugs that are equally – or more – efficacious than on-patent therapies.
As the population ages and the number of available pharmaceutical therapies continues to expand, polypharmacy rates are likely to rise without consistent scrutiny of safety, appropriateness and efficacy. The question facing the healthcare system is not whether medications have value, but which medications are demonstrably effective in what populations. Without meaningful intervention, the growing prevalence of polypharmacy will continue to generate clinical risk, financial burden and missed opportunities for therapeutic optimization. Whether through enhanced clinical guidelines or payment reforms, providers must ensure that each drug prescribed serves an intentional and achievable clinical purpose, rather than simply the clinical path of least resistance.