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Potentially inappropriate medication (PIM) prescribing in older adults is quite prevalent and is associated with an increased risk for adverse drug events, morbidity, and utilization of health care resources. In the acute care setting, PIM prescribing can be even more problematic due to multiple physicians and specialists who may be prescribing for a single patient as well as difficulty with medication reconciliation at transitions and limitations imposed by hospital formularies. This article highlights critical issues surrounding PIM prescribing in the acute care setting such as risk factors, screening tools, and potential strategies to minimize this significant public health problem.
The medication-use process is a complicated progression of steps traditionally consisting of prescribing, communicating orders, dispensing, administering, and monitoring.1 At each step, the potential for associated health risks exist; however, many preventable problems can occur at the initial prescribing stage.1 While no set definition has been established, inappropriate prescribing encompasses the use of medications that introduce a significant risk of an adverse drug event (ADE) when there exists evidence for an equally or more effective but lower-risk alternative therapy for treating the same medical condition.2 Additional situations also include over-use of medications at a higher frequency or for longer durations than clinically indicated, under-use of medically indicated medications based on ageist or irrational reasons, and use of multiple medications that have documented drug–drug interactions or drug–disease interactions.1,2
It is no surprise that inappropriate prescribing commonly occurs in adults aged 65 years or older, who have a higher prevalence of chronic disease, disability, and dependency than younger adults.3 While only 13% of Americans are aged 65 years or older, this group represents the largest per capita consumers of prescription medications.4,5 A recent survey of 3,500 community-dwelling adults found that over 29% take five or more prescription medications, 42% at least one or more over-the-counter medications, and 49% at least one or more dietary supplements.4 With increasing life expectancy, improved prescription drug coverage through the implementation of the Medicare Part D Prescription Drug Benefit Plan, and the emergence of over 50 new drugs per year into the United States (US) market, it seems likely that consumption of prescription drugs by older adults will continue to increase. Additionally, the continued development of life saving and lifestyle-saving medications, as well as direct to consumer marketing, seems to have created an excess dependence on medication therapy to solve everyday problems.
A number of studies have documented that potentially inappropriate medication (PIM) prescribing in older adults is common in the ambulatory setting, nursing homes, and the emergency department and that exposure to inappropriate medications is associated with increased morbidity, mortality, health care resource utilization, and ADEs.5 However, limited data exist regarding PIM prescribing in the acute care setting, although adults aged 65 years or older account for over 35% of annual hospital admissions.6–10 Older adults are also at increased risk for hospital readmission. An analysis of fee for service Medicare beneficiaries found that 19.6% of patients who had been discharged from a hospital were rehospitalized within 30 days, and 34.0% were rehospitalized within 90 days.11 Of note, the hospital environment can be particularly perilous for older adults. Hospitalization has been associated with a higher incidence of adverse outcomes including functional decline, delirium, and falls as well as ADEs in this population.12,13 A meta-analysis of 39 studies found an inhospital incidence of ADEs of 6.7% and an incidence of fatal ADEs of 0.3%, which may be slightly higher than what has been documented in the outpatient setting.14,15 Furthermore, older adults in the inpatient setting may be exposed to new and possibly unnecessary medications, multiple providers and specialists, and restrictive hospital formularies that require reconciliation with home medications; all of these can increase the risk for PIM prescribing.16,17
In order to address this public health concern in older adults, particularly within the hospital environment, it is crucial that clinicians have an understanding of potential risk factors for PIM prescribing, advantages and limitations of validated drug evaluation tools for identifying PIM prescribing, and possible strategic approaches to curtailing the problem.
No research has yet identified clear risk factors specific to PIM prescribing in the hospitalized older adult, but it may be possible to extrapolate from an evaluation of the root causes for ADEs to develop a potential list. Data in hospitalized patients suggest that advanced age (≥85 years), polypharmacy, and number of comorbidities can contribute to an increased likelihood of ADEs.18–21
While complex issues surrounding frailty, social and emotional infrastructure, and economic status can influence inappropriate prescribing, the major impact of advanced age lies in the context of altered pharmacokinetics (drug absorption, distribution, metabolism and excretion), altered pharmacodynamics (physiological effects of the drug) and age-related changes in body composition and physiology. With advanced age, lean body mass and total body water decrease, with a relative increase in total body fat. Such changes lead to a decreased volume of distribution for hydrophilic, narrow therapeutic drugs such as lithium and digoxin for which unadjusted dosing can result in higher plasma concentrations and possible toxicity. Conversely, lipid-soluble drugs such as long-acting benzodiazepines have an increased volume of distribution, thereby delaying their immediate effects and resulting in potentially dangerous accumulation with continued use.22
Advanced age is also associated with a reduction in hepatic mass and blood flow. Drugs such as beta-blockers, nitrates, and tricyclic antidepressants (TCAs) that exhibit significant hepatic first pass metabolism may have a higher bioavailability and faster onset, which will warrant initiation at lower doses with possible extended administration intervals. Cytochrome P450 oxidation also declines, increasing the risk for toxicity and possible drug – drug interactions for drugs that are substrates of these enzymes.23 With aging also come associated changes in renal structure and subsequent altered drug excretion. Drug dosages eliminated via the kidneys should be adjusted for compromised renal function. If serum albumin is decreased, the active unbound drug concentration will increase for highly protein-bound narrow therapeutic drugs such as phenytoin, theophylline, warfarin, and digoxin.
Finally, aging is also associated with changes in the end-organ responsiveness to drugs at receptor or post-receptor levels. There is decreased sensitivity to beta-receptors along with a possible decreased clinical response to beta-blockers and beta-agonists. The central nervous system becomes more vulnerable in the elderly to agents that affect brain function (eg, opioids, benzodiazepines, and psychotropic drugs).24
While treatment of multiple chronic diseases may justify the use of several drugs concomitantly, polypharmacy is associated with an increased risk for ADEs as well as drug-drug and drug-disease interactions.25 Goldberg and colleagues found that patients taking two drugs face a 13% risk of adverse drug–drug interactions, rising to 38% for four drugs and to 82% if seven or more drugs are given simultaneously.26 Duplicate prescribing within the same drug class is prevalent and frequently unrecognized.25,26 ADEs are often treated with additional drugs, leading to prescribing cascades.25 Polypharmacy can also augment the risk for medication non-adherence, which in turn can lead to suboptimal therapeutic effectiveness and poor clinical consequences.27 If providers do not recognize the existence of medication nonadherence, they may increase the dose of the initial medication or add a second agent, increasing not only the cost of therapy but risk for an ADE. It is clear that the use of multiple medications is associated with an increase in the risk of ADEs. However, the use of specific medications, such as atypical and typical antipsychotics as well as benzodiazepines should be of particular concern as well, as these medications are associated with decreased patient functioning and increased morbidity and mortality.3,28–30
Among adults aged over 65 years, 84% present with two or more chronic conditions, compared with 35% of patients aged 45 to 65 years.31 Data have shown that having three or more comorbities can increase the risk for having a severe ADE by 2.9–12.6-fold.20 The pervasiveness of comorbidity is especially apparent in hospitals. In the hospital setting, 60% of inpatients had at least one comorbidity, and 37% had two or more.32 The leading comorbities were hypertension (29.4%), chronic obstructive lung disease (COPD) (12.1%), diabetes mellitus (11.8%), fluid/electrolyte disorders (11.7%), iron deficiency/anemia (7.9%), and heart failure (5.7%). With each comorbidity comes additional exposure to a larger number of medications as well as new prescribers and specialists.32 For example, a Medicare beneficiary with heart failure may see on average 15–23 different providers within a given year.33 In this scenario, communication between providers, flawless transitions of care, and the overall coordination of care are crucial, as failure in any of these steps could lead to duplication of medications, prescribing of unnecessary medications, and drug – drug interactions.
Appropriateness of prescribing can be assessed by process or outcome measures that are explicit (criterion-based) or implicit (judgment-based).5 Explicit indicators are usually developed from published reviews, expert opinions, and consensus techniques. These measures are usually drug or disease oriented and can be applied with little or no clinical judgment. Unfortunately, explicit criteria may not take into account all quality indicators of health care as defined by national guidelines for an individual patient and their preferences, nor do they address the burden of comorbid conditions. In implicit approaches, a clinician employs patient-specific information and published evidence to form judgments about appropriateness. The focus is placed on the patient rather than on drugs or diseases. Implicit approaches are potentially more sensitive and can account for patients’ preferences, but they are time-consuming, depend on the users’ knowledge and attitudes, and can have low reliability. While no ideal measure exists, the strengths and weaknesses of both approaches should be taken into account. Presently, four tools exist to evaluate PIM prescribing in older adults.5 The Beers’ Criteria, Improved Prescribing in the Elderly Tool (IPET), and Screening Tool of Older Persons (STOPP) are explicit approaches, while the Medication Appropriateness Index (MAI) is an implicit model.
In 1991, Beers and colleagues published the first set of explicit criteria for determining PIM use in nursing home residents.34 Based on consensus opinion from experts in geriatric medicine, long-term care, geriatric and psychogeriatric pharmacology and pharmacoepidemiology, they devised a list of 30 medications that should be avoided in nursing home residents regardless of diagnoses or dose and frequency of medication use. This list incorporated certain psychotropic medications, antihypertensives, oral hypoglycemic agents, nonsteroidal anti-inflammatory drugs (NSAIDs), and analgesic agents. In 1997, Beers published a revised and more comprehensive set of explicit criteria for potentially inappropriate drug use in ambulatory people aged 65 years or older.35 The revised criteria were designed to be applicable to all adults aged 65 years or older regardless of their place of residence (community or nursing home) or level of frailty. The criteria divided potentially inappropriate drugs into three categories: drugs that generally should be avoided in older adults; doses, frequencies, or durations of specific therapies that vary from those generally accepted as appropriate use in elderly persons; and drugs to be avoided in combination with a specific co-morbidity. Beers’ criteria were again updated in 2003.36 The criteria specify PIMs both independent of diagnosis and condition (Table 1) and also by specific diagnosis and condition (Table 2). The new criteria included additions to the general list of inappropriate medications (eg, nitrofurantoin, doxazosin, and amiodarone). Fifteen medications and medication classes were removed from the 1997 list, eg, the use of beta-blockers (with exception of propranolol) in those with COPD, asthma, peripheral vascular disease and syncope or falls. The co-morbidity list in turn included new diagnoses such as depression, Parkinson’s disease, cognitive impairment, and incontinence.
In the US, the Beers’ criteria have become the most popular and accepted explicit tool used for evaluating PIM prescribing. In fact, many health plans and pharmacy benefit managers have adopted the Beers’ criteria or a modification of the list to help identify and target elderly members at risk of ADEs associated with PIM prescribing. Beginning in 2006, the National Committee for Quality Assurance has included a Health Plan Employer Data and Information Set (HEDIS) performance measure for the managed care industry to use to evaluate the percentage of members aged 65 years or older who receive medications that should be avoided. The specifications for this HEDIS performance measure are based on the Beers criteria with some modification.37,38
Numerous research studies have employed the Beers’ criteria to evaluate PIM prescribing and ADEs in the inpatient setting. Using the most updated Beers’ criteria, Gallagher and colleagues found that of the 597 admissions admitted to an Irish university teaching hospital, inappropriate prescribing occurred in 32% of elderly inpatients in which 24%, 6%, and 2% were taking one, two, or three inappropriate medications, respectively.39 Forty-nine percent of patients with inappropriate prescriptions were admitted with ADEs from the inappropriate medication, and 16% of all admissions were associated with such adverse effects. In a US study, Rothberg found that of 493,971 hospitalized elderly, 49% received at least one inappropriate prescription and 6% received three or more. The most common inappropriate medications prescribed consisted of promethazine, diphenhydramine, and propoxyphene.8 However, controversy exists regarding exposure to PIMs and ADEs. In a study of 389 elderly inpatients, Page and Ruscin demonstrated that while 27.5% of inpatients received a drug listed on the Beers’ criteria and 32% did experience an ADE, only 9.2% of ADEs were attributed to a Beers’ criteria medication.40 In fact, after controlling for covariates, prescription of a Beers’ criteria medication was not significantly associated with experiencing an ADE, discharge to higher levels of care, or in-hospital mortality.
The use of a list of medications, such as the Beers’ criteria, as a sole measurement for PIM prescribing has disadvantages. First, the inclusion of some drugs is subject to controversy, and insufficient evidence exists to support inclusion of some drugs presently on the Beers’ medication list. Second, the prescription of drugs that should be avoided is a relatively minor problem when compared with other categories of inappropriate prescribing such as under-and over-use of medications, drug–drug interactions, drug disease interactions, or drug duplication. The Beers’ criteria do not address any of these facets. Third, the reliability of the process to generate such lists is not established. Fourth, while the Beers’ criteria may be easy to use, they lack comprehensiveness, organization, and structure.
Referred to as the “Canadian Criteria”, the IPET consists of a list of the 14 most prevalent prescription errors identified from a long list of inappropriate prescription instances drawn up by an expert Canadian Consensus Panel in 1997 (Table 3).41 The IPET was initially validated in a prospective study of acutely hospitalized elderly patients that demonstrated PIM prescribing in 12.5% of patients.41 However, little use of this instrument exists outside of Canada with the exception of one Irish study that found that 22% of acutely hospitalized elderly were taking at least one inappropriate prescription medication at the point of admission.42 Furthermore, as with the Beers’ criteria, insufficient convincing evidence exists regarding IPET’s efficacy to reduce ADR incidence, reduce excessive health resource utilization or decrease mortality. The IPET only cites 14 instances of inappropriate prescribing, three of which relate solely to TCAs, which are infrequently used in today’s medical practice. Furthermore, the IPET is outdated as it recommends against the use of beta-blockers in heart failure contrary to current guidelines and published evidence. Finally, IPET is heavily weighted towards cardiovascular drug use, psychotropic drug use, and NSAID use and is not organized in any particular order or structure.
Developed by a multidisciplinary team of Irish geriatricians, pharmacists, pharmacologists, and primary care physicians, the STOPP incorporates commonly encountered instances of PIM prescribing in older adults that include drug–drug and drug–disease interactions, drugs that adversely affect older patients at risk of falls, and duplicate drug class prescriptions (Table 4).43 Its criteria are arranged according to relevant physiological systems for ease of use, and each criterion is accompanied by a concise explanation as to why the prescription is potentially inappropriate.43
The performance of the STOPP and Beers criteria has been evaluated for detecting PIM prescribing and related ADRs in 715 older patients admitted a university teaching hospital in Ireland.44 The STOPP identified 336 PIMs affecting 35% of patients, one-third of whom presented with an associated ADE, while the Beers’ criteria identified 226 PIMs affecting 25% of patients, of whom 43% presented with an associated ADE. The STOPP-related PIMs contributed to 11.5% of all admissions, while the Beers’ criteria-related PIMs contributed to significantly fewer admissions (6%). The most common PIMs identified by STOPP included use of long-acting benzodiazepines, TCAs with clear-cut contraindications, first generation antihistamines, vasodilator drugs known to cause hypotension in patients with persistent postural hypotension, inappropriate use of NSAIDs and opiates, and duplicate drug class prescriptions such as two angiotensin converting enzyme inhibitors, two NSAIDs, two selective serotonin reuptake inhibitors or dual antiplatelet therapy without indication. The authors concluded that compared to the Beers’ criteria the STOPP criteria are more sensitive in identifying patients liable to suffer harm from an ADE because of PIM prescribing.
The advantages of the STOPP consist of good inter-rater reliability, inclusion of both American and European medications, organization and structure based physiological systems, and short time to complete (~3 minutes). However, this European tool needs to be evaluated in additional studies and in other settings.
Initially developed by Dr Joseph Hanlon and colleagues, the MAI is a validated measure of prescribing appropriateness that assesses ten elements of prescribing: indication, effectiveness, dose, correct directions, practical directions, drug–drug interactions, drug–disease interactions, duplication, duration, and cost.45 While this implicit approach requires clinical judgment to assess criteria, the index has operational definitions and explicit instructions, which standardize the rating process. The ratings generate a weighted score that serves as a summary measure of prescribing appropriateness ranging from 0 to 18 (0 = no item inappropriate; 18 = all items inappropriate). Three components of the MAI (indication, effectiveness, and duplication) can be used to detect unnecessary polypharmacy and PIM prescribing.17,46
In an evaluation of 11 Veterans Affairs Medical Centers involving 397 frail elderly inpatients, Hanlon and colleagues found that 92% of subjects had at least one drug with one or more inappropriate ratings. The most common problems involved expensive drugs (70%), impractical directions (55.2%), and incorrect dosages (50.9%).6 The most prevalent medication classes with appropriateness concerns consisted of gastric (50.6%), cardiovascular (47.6%), and central nervous system (23.9%) agents. In a similar inpatient population, Hajjar and colleagues found that 44% of frail elderly inpatients had at least one unnecessary medication at discharge.17 From their analysis, the factors most commonly associated with unnecessary drug prescribing consisted of hypertension diagnosis, multiple prescribers, and nine or more medications.
The MAI as a tool to evaluate PIM prescribing has major advantages: it has been tested in both the inpatient and ambulatory settings, exhibits excellent intra-rater and inter-rater reliability, and has face and content validity. It addresses multiple components of prescribing appropriateness, and can be applied to every medication in the context of patient-specific characteristics. However, the tool is more time-consuming to complete (~10 minutes per drug assessed) and does not assess under-prescribing (untreated indications).46 Most studies using the MAI have been performed in a single setting, with groups of elderly veterans from the Veterans Affairs Medical Center in Durham, North Carolina. As with other tools developed to date, the index needs to be validated in other populations and settings before being used universally.
Conceptually, PIM prescribing in the inpatient setting is a multi-faceted function of the patient, prescriber, and environment. First, the clinical needs of the patient must be the primary determinant of prescribing decisions. Appropriate prescribing should aim to promote the use of evidence-based therapies while minimizing the use of medications for which there is no clinical need, questionable evidence, or duplication. The patient’s perceptions and preferences should also be considered. Second, prescribing is done mainly by providers who use their own clinical experience and attitudes in making medication decisions. Factors that contribute to PIM prescribing include inadequate training in geriatric pharmacotherapy as well as the absence of communication between providers practicing in different settings, or between specialists and the primary care provider. Finally, the environment in which the prescriber operates can affect prescribing decisions. Unfortunately, the acute care setting does not encourage review of chronic and preventive medications. Furthermore, the inpatient environment may lack the technological infrastructure to share information relating to drugs during transitions of care, which ultimately compromises quality.
With this in mind, several strategic approaches exist to potentially minimize PIM prescribing. The question surrounding which tool to use to measure quality of prescribing remains controversial. Quality measures are often chosen not only because of the clinical importance of the construct they measure but also their ease of use. In particular, drugs-to-avoid criteria have been a popular tool for research, in part due to their easy applicability to administrative databases. Although easy-to-administer measures such as drugs-to-avoid criteria (eg, Beers’ criteria) capture useful elements of prescribing quality, that the relative ease of these metrics creates an immediate danger that they will drive quality assessment and improvements efforts rather than vice versa. In fact, significant discordance exists between the MAI and Beers’ criteria when using these tools to evaluate drug prescribing quality in similar populations.47 Furthermore, when prescribing, one must take into account the patient as a whole, including his or her life expectancy and quality of life within a social and economical environment, select essential medications, and avoid drugs with a poorer benefit-to-risk ratio. Unfortunately, explicit prescribing criteria may force the prescriber to ignore these considerations by prescribing at the bedside according to inflexible, rigid guidelines. Therefore, based on these observations, because using a single tool may fail to capture the overall quality of a patient’s medication regimen, it would seem prudent to consider employing multiple tools and multifaceted perspectives to capture the range of quality problems that may be present in medication prescribing.
While primarily documented in the ambulatory setting, additional strategies for hospital settings consist of using a computerized decision support system, implementing didactic educational programs within the health system, utilizing clinical pharmacist expertise on clinical rounds or for prospective medication review, and considering a comprehensive geriatric evaluation and management (GEM) care approach.5,48–56 This latter approach consists of a multidisciplinary team, which may include a geriatrician and other health care providers with specialized geriatric training (eg, nurses, pharmacists, dieticians, social workers, and psychologists). Data from the inpatient setting suggest that employing a GEM care team can lower potential drug-drug interactions and the number of unnecessarily prescribed drugs from admission to discharge, as well as decrease the time to discharge.5,52–54 Finally, infrastructure and hospital policies to provide medication reconciliation on admission and at discharge are crucial in response to medication discrepancies within the inpatient setting documented as problematic. Coleman and colleagues found that 14% of older community-dwelling patients experienced post-hospital medication discrepancies within two weeks of discharge, and that half of those discrepancies were system-related.16 Presently, medication reconciliation is included in the Joint Commission’s National Patient Safety Goals. Goal 8 states that hospitals must “accurately and completely reconcile patient medications across the continuum of care.”57 In order to prevent fragmentation of care from the inpatient to the outpatient setting, clinical pharmacists and nurses have served as potential medication transition coordinators and discharge advocates. Data from two studies suggest that such an approach can lower the rate of hospital readmission and emergency department visits.50,58
The prescribing of medications is a fundamental component of the care of the elderly, and the optimization of drug prescribing has become an important public health concern. The inpatient setting can be particularly hazardous regarding ADEs due to the problem of multiple prescribers, medication reconciliation issues, and poor communication between outpatient and inpatient providers. While tools are available to identify PIM prescribing and potential strategies exist to curtail the problem, several fundamental issues still exist. First, from an interventional and health care research perspective, even though data provide useful insights into the effectiveness of different approaches, the effect on important health outcomes and health care costs still needs to be evaluated. Second, despite substantial resource dedication to developing and testing the effectiveness of interventions to improve prescribing, widespread diffusion of successful methods has not yet been achieved. It also seems that our current culture, from the perspective of patients and prescribers, relies too heavily on pharmacological interventions to address medical problems. The use of medications is often the first and only intervention sought, when other proven interventions, such as psychotherapy for behavioral and mental health issues, may be appropriate. Also, to fully address appropriateness of prescribing, not only should the use of inappropriate medications be avoided, but the use of indicated and beneficial medications should be encouraged. In this instance, evidence-based criteria, such as the START (Screening Tool to Alert doctors to Right Treatment) criteria should compliment assessments.59 Finally, the responsibility of appropriate prescribing should no longer fall solely on the shoulders of physician prescriber. Rather the responsibility should be shared across the multidisciplinary continuum of care with all health care professionals who provide care for the older adult.
The authors report no conflicts of interest in this work.