The global proportion of older adults is rising due to increased life expectancy and declining birth rates.¹⁾ This trend is accompanied by a rise in the number of frail individuals with multimorbidity.²⁾ Socioeconomic development has improved access to healthcare systems, and advancements in medical technology have led to increased utilization of healthcare services. As societies continue to age, the frequency of healthcare contacts among older adults is expected to grow.³⁾ This increase in healthcare utilization often results in more medication prescriptions, and older adults with multiple chronic conditions are particularly vulnerable to polypharmacy, where they are exposed to the simultaneous use of multiple medications.⁴⁾

All medications have potential side effects, and older adults are more susceptible to these adverse effects compared to younger individuals.⁵⁾ Age-related physiological changes affect pharmacokinetic processes (absorption, distribution, metabolism, and excretion) and pharmacodynamic responses, often leading to different adverse outcomes than those observed in younger, healthier adults. Moreover, frail older adults are more likely to suffer from frequent and severe adverse drug reactions due to underlying pathologies.⁶⁾ Multimorbidity increases the likelihood of drug-disease and drug-drug interactions, further complicating medication management.⁷⁾

Among the various medications, those that frequently cause adverse effects in older adults and whose risks outweigh their benefits are classified as potentially inappropriate medications (PIMs).⁸⁾ Efforts to reduce polypharmacy and PIM prescriptions have led to the development of PIM lists and guidelines, such as the American Geriatrics Society's Beers Criteria and the European Geriatric Medicine Society's STOPP/START Criteria, which recommend safer alternatives.^9,10) Older adults prescribed multiple medications require careful attention to avoid suboptimal treatment that includes PIMs. Despite these efforts, studies from various countries report high rates of polypharmacy (30.2%–61.7%) and PIM use (23.6%–47.0%) among older adults.^11,12)

To mitigate polypharmacy and the prescription of PIMs in older adults, and to establish optimal medication guidelines and better policy alternatives, it is essential to understand the status and temporal trends of polypharmacy and PIM use.¹³⁾ Analyzing these trends requires considering not only frailty and comorbidity, which significantly influence medication use, but also demographic characteristics of the population.¹⁴⁾ Although there have been cross-sectional studies and small-scale longitudinal analyses examining frailty, polypharmacy, and PIM prescriptions, there is a lack of large-scale population-based studies. This study specifically focuses on the 66-year-old population, as this age represents a critical transition into older adulthood in South Korea. It is not only the age of eligibility for the National Screening Program for Transitional Ages (NSPTA) but also often coincides with major life events such as retirement and subsequent changes in social and economic status. Medically, it is a period where chronic conditions that may have developed in middle age begin to accumulate, often marking the onset of significant polypharmacy. Analyzing medication patterns at this pivotal age is therefore crucial for developing early, preventative strategies to mitigate medication-related harm throughout the later stages of old age. Therefore, we conducted a comprehensive analysis of polypharmacy and PIM prescription rates, as well as participant characteristics including frailty and comorbidity, and demographic characteristics among 66-year-old participants of the NSPTA in Korea from 2012 to 2021.

The researchers conducted a repeated cross-sectional study on approximately 3.4 million individuals aged 66 who underwent NSPTA between 2012 and 2021, as they entered older adulthood. The study revealed that individuals residing in counties had higher rates of polypharmacy compared to those residing in large cities. Additionally, a higher rate of polypharmacy prescriptions was observed among individuals in the lowest income quintile, medical aid beneficiaries, those with multiple comorbidities, and frail individuals. The frequency of PIM prescriptions exhibited similar patterns to polypharmacy use, with higher rates among county residents, those in the lowest income quintile, medical aid beneficiaries, and individuals with multiple comorbidities or frailty.

An analysis of the temporal trends among 66-year-olds in Korea from 2012 to 2021 revealed a gradual decrease in comorbidity burden, an improvement in frailty, and a decline in the proportion of individuals making more than 30 outpatient visits per year. However, the proportion of individuals with polypharmacy increased slightly during this period, as did the frequency of hyper-polypharmacy. The increase in polypharmacy rates was more pronounced among county residents compared to those in large cities, and among individuals in the lowest income quintile compared to those in the highest quintile. Notably, medical aid beneficiaries experienced a substantial increase of over 10% in polypharmacy rates over the ten-year period. While the proportion of PIM users decreased slightly over time in most groups, it increased specifically among medical aid beneficiaries. The list of PIMs remained relatively consistent throughout the study period, with NSAIDs, PPIs, skeletal muscle relaxants, and anxiolytics/hypnotics ranking among the most frequently prescribed PIMs.

The findings of this study illustrate the complex dynamics of medication use among older adults in Korea. Over time, frailty and comorbidity burden among the 66-year-old population improved, and the proportion of individuals requiring frequent outpatient visits declined. However, the proportion of polypharmacy users increased, with a particularly marked rise in polypharmacy and hyper-polypharmacy among vulnerable populations. Moreover, while PIM use decreased in most groups, it increased among medical aid beneficiaries. This concerning trend may be attributable to several factors. Disparities in health literacy could mean that vulnerable populations have a lower understanding of the risks associated with polypharmacy and PIMs. Additionally, regional differences in healthcare, such as limited access to geriatric specialists in rural areas, may lead to less comprehensive medication management. Finally, the low co-payment structure for medical aid beneficiaries in Korea might inadvertently encourage more frequent healthcare visits and trials of various medications, increasing their exposure to polypharmacy and PIMs.

These trends highlight the need for targeted interventions that are specifically tailored to population characteristics. Previous studies have already demonstrated the impact of inequalities in residential area, education, income, and employment on polypharmacy and PIM use.^20,21) Our study not only confirms these findings but also reveals a decade-long trend of widening disparities despite overall improvements in comorbidity and frailty, which reinforces the urgent need for policy adjustments to effectively address these inequalities.

The increasing prevalence of polypharmacy in Korea during the study period is consistent with findings from previous studies conducted in other countries.^22,23) The increase in the proportion of individuals prescribed polypharmacy and hyper-polypharmacy may be due to the growing number of health conditions and related indicators requiring management, driven by advancements in medical technology, and increasingly stringent single disease-focused guidelines. Previous studies have also noted a significant rise in polypharmacy rates over time, particularly among older adults with cardiovascular disease or diabetes.^23,24) Moreover, Korea’s fee-for-service healthcare system, which primarily incentivizes diagnostic testing, monitoring, and medication prescription rather than prevention, education, or lifestyle modification, may have contributed to the rising prevalence of polypharmacy. The limited reimbursement for preventive measures and lifestyle interventions further underscores the potential influence of this system on the increasing rates of polypharmacy.^25-27)

The prescription rate of PIMs decreased slightly from 55.7% in 2012 to 53.7% in 2021. Despite this modest decline, the persistently high prevalence of PIM use above 50% represents a critical public health concern, particularly as this was observed in relatively younger older adults (age 66). This suggests that approximately half of the individuals entering older adulthood are exposed to medications with unfavorable risk-benefit profiles, potentially setting a trajectory for increased adverse drug events and healthcare costs as they age. Moreover, considering that PIM prescription rates in other countries range from 30% to 50%, the rate observed in this study remains alarmingly high.^12,28,29) Although South Korea has implemented a nationwide real-time Drug Utilization Review (DUR) system since 2015, which has yielded some positive outcomes, our findings strongly suggest that this policy alone is insufficient to adequately address this issue.³⁰⁾ This underscores the urgent need for more proactive and multifaceted interventions. Specifically, the high frequency of prescriptions for NSAIDs, PPIs, skeletal muscle relaxants, and anxiolytics/hypnotics is often linked to patients’ preference for medication over non-pharmacological approaches for even minor symptoms.³¹⁾ Therefore, a crucial part of the intervention should focus on shifting the perception that all temporary discomforts require pharmacological management. Furthermore, when these PIMs are necessary, a key strategy must be to limit their use to the shortest possible duration. Given the increasing absolute number of individuals taking PIMs due to the aging population, the continued attention of healthcare policymakers is also warranted.³²⁾

While numerous studies have reported on the prevalence and user characteristics of polypharmacy and PIM use in older adults, most investigations to date have been conducted as cross-sectional studies examining specific populations at particular points in time. This has led to difficulties in conducting direct time-series analyses across multiple studies due to variations in the operational definitions of polypharmacy and PIM, specific study populations, and investigation periods. This study, a repeated cross-sectional study, investigated the trends in polypharmacy and PIM prescribing among 66-year-old individuals who underwent the NSPTA annually from 2012 to 2021, using consistent criteria for both. With approximately 80% of eligible individuals participating, this study facilitated time-series analysis as a birth cohort.³³⁾ Furthermore, it holds significance as the first nationwide study to investigate trends in the prevalence of polypharmacy and PIM use among older adults according to residence, income level, comorbidity burden, frailty, and insurance type.

However, several limitations should be considered. This study focused on individuals aged 66 who had just entered old age each year for 10 years, and thus may not be representative of the entire older adult population. Injectables and topical medications were excluded from the analysis, and over-the-counter drugs were not included because the analysis was based on health insurance claims data. Therefore, the prevalence of polypharmacy or PIM use may have been underestimated. Additionally, because the analysis was based on prescription records submitted to the NHIS, it was impossible to confirm patient adherence. We also could not validate the recorded diagnoses against clinical records or identify the specific grounds for each prescription. A medication classified as a PIM might have been clinically justified for an individual patient if, for example, no viable alternatives existed, or the benefit outweighed the risk. The study period included the COVID-19 pandemic, which may have affected polypharmacy and PIM prescribing. Furthermore, the findings of this study are specific to the South Korean healthcare system, with its unique insurance policies and prescribing culture, and thus should be generalized to other countries with caution. Finally, although the Beers Criteria and STOPP/START criteria were revised during the study period, resulting in changes to the PIM lists of the two research institutions, the final PIM list was used retrospectively.

In conclusion, an analysis of 66-year-olds from 2012 to 2021 revealed that polypharmacy and PIM use were more prevalent among individuals residing in rural areas, medical aid beneficiaries, and those with lower income levels. Although comorbidity burden and frailty among 66-year-olds improved over time, the proportion of polypharmacy users increased overall, with a notably larger increase among rural residents and socioeconomically disadvantaged groups. During the same period, the proportion of PIM users decreased slightly; however, an increasing trend was observed among medical aid beneficiaries. These findings suggest that health policymakers need to enhance and improve existing systems, such as the DUR program, and urgently develop quality improvement strategies to reduce polypharmacy and PIM use among specific population groups. These tailored interventions, by ensuring safe medication use, could play a crucial role in preventing disease, minimizing disability, and reducing the potential for iatrogenic harm from medications in an aging society.