In January 2018, approximately 7.4 million Koreans (14.3% of the total population) were ≥65 years of age.¹⁾ Korea has just entered the aged society phase and the growth rate of this aging population is among the most rapid worldwide. The proportions of older adults ≥65 years of age are expected to be 20% in 2026, 30% in 2034, and over 40% in 2058.²⁾

Older patients generally use more drugs than younger people. Changes in pharmacokinetics and pharmacodynamics, poor homeostatic reserves, and increased frailty significantly increase the risk of adverse drug events (ADEs) in older populations.³⁾ Although statistical data about ADEs in older Koreans are limited, the United Kingdom and the United States studies showed that ADEs are a common cause of morbidity and mortality in older patients. In two UK hospitals, ADEs accounted for 6.5% of hospital admissions and patients admitted with ADEs were significantly older than patients without ADEs.⁴⁾ A US study also reported that ADEs are responsible for about 100,000 hospitalizations per year in adults ≥65 years of age and nearly half of these hospitalizations were among adults ≥80 years.⁵⁾ In addition, the prediction and detection of ADEs is challenging in older adults and far more difficult in patients with cognitive impairment.⁶⁾ Therefore the impact of ADEs could be underestimated in older populations. Furthermore, fragmented medical services in the Korean health system⁷⁾ suggest that ADEs among older Koreans may be an even more serious problem compared to other countries.

Medications whose risk of ADEs outweighs their expected clinical benefit when they are administered to older persons are considered potentially inappropriate medications (PIMs), especially when there are better-tolerated alternatives.⁸⁾ However, there is no widely-used, reliable PIMs list in Korea. Explicit criteria for screening PIMs that have been developed in other countries, such as the Beers criteria, are difficult to apply in Korean older people because of the differences in drug availability and prescribing behavior. The domestic PIMs list that Kim et al.⁹⁾ proposed in 2010 has not been used widely because the list was developed without the collaboration of geriatric academic societies and has not been disseminated effectively to doctors who prescribe medication to older people. The objective of this study was to develop a concise PIMs list to which Korean doctors who treat older people can easily refer in their daily practice.

A research steering team was formed to recruit experts and prepare and circulate the content of the Delphi rounds. The team comprised 2 geriatricians, a family physician, a Delphi method expert, and a public health researcher. The final PIMs list was produced through 4 rounds of comprehensive structured expert surveys distributed through email (modified Delphi method).

The final PIMs list is presented in Tables 1 and 2. The list targets older adults outside palliative care and includes medications that most older adults (Table 1) and older adults with specific conditions (Table 2) should avoid. The expert panel emphasizes that the medications in this list are not “absolutely contraindicated” but “potentially inappropriate”; thus, the medications can be used cautiously for older adults if clinicians judge that the potential benefit outweighs the risk.

We present a new PIMs list for Korean older adults that was developed in collaboration with major geriatric academic societies in Korea. The list was generated with the modified Delphi method referring to recently published international screening tools such as the 2015 Beers criteria and the revised STOPP.

A prospective, observational cohort study showed that the self-reported history of falls (odds ratio, 1.23; 95% confidence interval [CI], 1.04–1.45) and hospital admission (hazard ratio, 1.16; 95% CI, 1.08–1.24) were independently associated with the use of PIMs in community-dwelling older men.¹⁴⁾ Hamilton et al.¹⁵⁾ also showed in a European prospective study that the prescription of PIMs according to the original STOPP criteria was significantly associated with ADEs that cause or contribute to hospital admission in older adults. With the rapid increase of older populations, several studies regarding PIMs have been also published in Korea. Hwang et al.¹⁶⁾ reported that 58.2% of residents in long-term care facilities had received at least one PIM according to the 2012 Beers criteria and that the most prevalent PIMs were quetiapine, chlorpheniramine, risperidone, and zolpidem. A recent Korean retrospective study suggested that patients administered PIMs (defined using the 2012 Beers criteria) were more likely to be admitted to the hospital or visit emergency departments (ED).¹⁷⁾ In that study, the most commonly used PIMs were chlorpheniramine, diazepam, metoclopramide, and diclofenac. Although most Korean studies examining PIMs have used the Beers criteria, 38 of 111 drugs (34.2%) considered PIMs according to the 2015 Beers criteria are unavailable in Korea. Due to the absence of a Korean PIMs list, it is hard for physicians to apply a PIMs screening tool in their daily practice. The 2010 Kim’s list has been the only published PIMs list for Korean older adults until now. However, it lacked a description of the applicable conditions or exceptions for each item and included some out-of-date items such as beta-blockers for heart failure and unavailable drugs such as tacrine, dipyridamole, and disopyramide.⁹⁾ Therefore, an updated list was required to incorporate recent advances in this field.

As there is no official geriatric training system in Korea, many Korean doctors might be unfamiliar with PIMs for older adults. For this reason, the expert panel agreed to provide a concise rather than exhaustive list, which can be easily adopted by doctors who treat older people, including primary care physicians and surgeons. To reduce the number of PIMs items, the research steering team excluded items with CSS <9 points, with the possibility of re-entry in further Delphi rounds. We also merged some conditions sharing similar PIMs; for example, dementia with delirium, and history of falls with syncope and postural hypotension. Finally, we were able to produce a concise list including 62 general PIMs and 48 PIMs for 18 specific conditions compared to the 2015 Beers criteria, which included 113 general PIMs, 68 PIMs for 12 specific conditions, and 16 PIMs with caution. Despite the small number of items, the new list addresses common ADEs in the older population such as falls and cognitive problems,¹⁸⁾ and also includes most of the prevalent PIMs in Korea.^16,17) To reflect the fact that gastrointestinal bleeding is a major ADE causing hospitalization or ED visit,^4,5) the panel included aspirin in older adults aged ≥80 years for cardiovascular primary prevention and aspirin plus clopidogrel for secondary stroke prevention in the list. The panel also suggested less stringent glycated hemoglobin targets (<7.5% or higher) for older patients with diabetes as a comment to reduce hypoglycemic events, which is another major cause of hospitalization related to ADEs.¹⁹⁾

Some panelists were skeptical about the inclusion of antipsychotics in this list because nonpharmacological options such as behavioral intervention for Behavioral and Psychological Symptoms of Dementia management are rarely available in Korean hospitals and long-term care facilities. However, with increasing evidence of harm associated with antipsychotics²⁰⁾ and conflicting evidence on their effectiveness,²¹⁾ the expert panel agreed that antipsychotics should be included in the list with the comments, “Short-term and low-dose antipsychotic (such as haloperidol, risperidone, and quetiapine) use might be appropriate for delirium or dementia if nonpharmacological options (e.g., behavioral interventions) have failed or are not possible and the older adult is threatening substantial harm to self or others.” Apart from this list, the multifaceted effort to reduce antipsychotics use especially in a long-term care setting is urgently required in Korea. There was substantial concern regarding the use of over-the-counter drugs containing first-generation antihistamines and herbal medicine in older adults, but the panel excluded these items from the final list because they could have too wide and vague range of application without concrete evidence. The panel did not reach a consensus regarding megestrol until the final round of survey and it was, thus, excluded.

This study has several limitations. Because of limited resources, we generated the preliminary list without evidence review for each item but rather from the review of existing criteria, which could result in the omission of recently introduced items. However, in view of the limited number of methodologically high-quality studies of older patients, the Delphi method based on existing criteria has been acknowledged as an acceptable way to generate a domestic PIMs list.^22,23) Next, the relatively small number and low diversity of panel members was another limitation of the study; therefore, the additional participation of cardiologists, neurologists, and more primary care physicians and clinical pharmacists is required in future updates of the list. In addition, future updates could consider drug-drug interactions and PIMs based on kidney function that were not addressed in this study to make the lists concise. Finally, there could be several exceptional clinical situations in which the drugs on this list should be prescribed for older patients. The expert panel tried to address this issue in the Delphi rounds and described typical exceptional situations for each item in comments, but they are not enough to cover diverse clinical settings. Therefore, this PIMs list is only a reference to support better clinical decisions in the prescription for older patients and cannot substitute for clinical decision-making in specific medical situations.

Computerized decision support, where electronic alerts are produced to guide the prescriber, is an effective intervention in improving medication prescription in older adults.²⁴⁾ In Korea, the nationwide drug utilization review (DUR) system was introduced in 2010 and the system is providing real-time safety alerts for prescribing long-acting benzodiazepines and TCA to older adults in outpatient clinics in Korea.²⁵⁾ It would be valuable to incorporate selected drugs from this list in the DUR after proper validation.

We hope that this explicit PIMs list helps Korean physicians to make individualized therapeutic decisions for their older patients and improve medication safety. Further prospective studies to validate its usefulness in various clinical setting and regular updating of the list are required.