Featured Report:
Improving the Quality of Geriatric Pharmacotherapy
(A-02) Full Text
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Prescribing for the Elderly |
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Pharmacoepidemiology of Drug Use in Geriatric Patients |
Suboptimal Prescribing |
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Pharmacokinetic and Pharmacodynamic Changes with Aging |
Appropriate Prescribing for the Elderly |
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Recommendations (Adopted AMA Policy and Directives) Table 1. Recommendations of the Surgeon General’s Medical Working Group (1988) |
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NOTE: This report of the American Medical Association (AMA) Council on Scientific Affairs (CSA), written in response to Resolution 503 (I-00), was presented as CSA Report 5 at the 2002 AMA Annual Meeting. It represents the medical/scientific literature on this subject as of June 2002. Literature searches were conducted in the MEDLINE database for English-language articles published between 1985 and February 2002 using the search terms aged or aging or geriatrics in combination with drug therapy; prescriptions, drug; pharmacokinetics; drug utilization review; pharmacology, clinical; self medication; or pharmaceutical services. A total of 1686 citations were identified and 503 were retrieved for analysis. Additional references were culled from the bibliographies of these references. Background Since the beginning of the 20th Century, life expectancy at birth in the United States has increased from less than 50 years to more than 76 years. From 1960 to 2000 there was an approximate doubling of people aged 65 years and older. By the year 2030, this number will double again to reach more than 70 million, constituting 20% of the population.1 As life expectancy increases, an ever-greater need exists to improve the health and quality of life of the aged. Discovering new treatment and prevention strategies and improving health behaviors and medication use will be required to accomplish this. Currently, the "Medicare generation" consumes nearly one third of all medications, and those over age 85--the group comprising the highest proportion of medically frail citizens--are the fastest-growing demographic segment in the country. These trends promise to further intensify the disproportionate use of medications in the elderly, particularly for chronic illness The elderly represent a special dimension of virtually all aspects of medication use, from basic pharmacology and drug testing to prescribing and utilization, reimbursement, and postmarketing surveillance. Data emerged in the 1960s and 1970s suggesting that age was a risk factor for the development of an adverse drug reaction (ADR).2 Spontaneous adverse reaction reports to the Food and Drug Administration (FDA) in the mid-1980s indicated that the rate of ADRs among persons aged 65 years or older was nearly double that of younger individuals.3 Subsequently, the problem of inappropriate prescribing of medications to older patients was widely acknowledged and publicized by professional societies, governmental organizations, advocacy groups for the elderly, and the media. The enactment and subsequent repeal of the Medicare Catastrophic Coverage Act of 1988 crystallized interest in this area. Several governmental regulatory and legislative initiatives occurred in the late 1980s and 1990s in an effort to improve the science base for policy-making and to decrease adverse drug events in geriatric patients.
Formal Graduate Medical Education in Geriatric Medicine Prescribers, dispensers, and monitors of medication must understand age-related changes affecting the disposition of drugs. Except for the obvious exceptions (eg, pediatrics), all graduate medical education programs and residencies accredited by the Accreditation Council for Graduate Medical Education (ACGME) provide specialty-specific education, training, and experience in the care of geriatric patients as a normal part of their programs of instruction. This is particularly true for the specialties of internal medicine and family practice. In a joint venture, the American Board of Internal Medicine and the American Board of Family Practice have offered a subspecialty certificate in Geriatric Medicine since 1988. The added certificate is designed to recognize excellence among those diplomates of the primary board who provide care to the elderly. A candidate for certification in Geriatric Medicine must be certified by one of the sponsoring boards, have undertaken 1 year of fellowship training in a program of geriatric medicine accredited by the ACGME, and have passed a cognitive examination. Certificates are time-limited for 10 years. Although 120 ACGME-accredited programs for residency training in geriatric medicine exist (97 associated with internal medicine residencies and 23 associated with family practice programs), they have not attracted many applicants. Only slightly more than 300 physicians are currently enrolled in these programs and less than one third of these are graduates of medical schools located in the United States. A reduction in the length of training to qualify for certification from 2 years to 1 year did not measurably increase the number of physicians in training. The 2001 Annual Report of the American Board of Medical Specialties (ABMS) indicates that in the 1991-2000 10-year period, 1,779 certificates in geriatric medicine were awarded by the American Board of Family Practice and 3,853 by the American Board of Internal Medicine. The small number of physicians undertaking additional training in geriatric medicine from the specialties of internal medicine and family practice is generally considered to reflect the adequacy of preparation to care for geriatric patients after completing the primary specialty program. Anecdotal commentaries indicate that certification in geriatric medicine may be seen as an academic credential for those planning a career in teaching. In addition to the certification offered by the American Board of Internal Medicine and the American Board of Family Practice, the American Board of Psychiatry and Neurology offers a subspecialty certificate in geriatric psychiatry. In addition to certification in psychiatry, an additional year of residency training in geriatric psychiatry at an ACGME-accredited program is required. There are 61 accredited programs in existence, with a total of 86 physicians in training. Twenty-seven percent are graduates of US medical schools. The ABMS indicates that the American Board of Psychiatry and Neurology has awarded 2,508 subspecialty certificates in the referenced 10-year period.Back to Top Pharmacoepidemiology of Drug Use in Geriatric Patients Patterns of Medication Use. Historically, it has been recognized that patients ³ 65 years of age take more drugs than younger adults, and that the number of drugs taken tends to increase with age.8,9 Nearly 75% of office visits by geriatric patients are associated with continuation or initiation of a drug prescription. The most recent data on the general patterns of medication use in the ambulatory population confirm that large numbers of US adults take large quantities of medications, in the ambulatory as well as institutionalized population. Rates of use increase with age and are greater in women than in men for most measures. Among individuals aged ≥65 years, 66% of men and 81% of women use at least 1 prescription drug weekly. One in 8 men and nearly 25% of women use ≥5 prescription drugs weekly. When over-the-counter (OTC) drugs and dietary supplements are included, 89% of men and 94% of women use at least 1 product weekly; 43% of men and 57% of women use 5 or more, and 11% to 12% of men and women use 10 or of these products weekly.10 The most frequently used OTC entities were analgesics (acetaminophen, ibuprofen, aspirin), pseudoephedrine, diphenhydramine, dextromethorphan, non-steroidal antiinflammatory drugs (NSAIDs), antihistamines, and H2-blockers. The most frequently used prescription drugs in this study were conjugated estrogens, thyroid supplements, diuretics, "statins," ACE inhibitors, progestins, nonsedating antihistamines, beta-blockers, calcium channel blockers, omeprazole, and warfarin. Overall, 16% of prescription drug users also used 1 or more dietary supplement. Other survey data suggest that community-dwelling older Americans take an average of 2.7 to 4.2 prescription and nonprescription medications.11 Historically, at discharge from the hospital older patients take a higher number of drugs (mean = 5), and nursing home residents take an even larger number.12-14 Adverse Drug Reactions in the Elderly. Avoidable ADRs are a serious consequence of inappropriate drug prescribing in the elderly. A meta-analysis of 34 studies spanning the 1960s to 1990s estimated that in 1994, more than 100,000 patients experienced a fatal ADR, and more than 2 million hospitalized patients experienced a serious ADR.15 Approximately 4.7% of hospital admissions are drug-related. This analysis included studies that used the World Health Organization’s definition of an ADR which is "any noxious, unintended, and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, or therapy." This definition excludes therapeutic failures, intentional and accidental overdoses, and drug abuse. It also does not include "adverse events" attributable to errors in drug administration or noncompliance. Although the accuracy and relevance of these estimates to contemporary practice has been questioned, there is general agreement that ADRs are an important problem. Once in the hospital, ADRs occur in 6.5% of patients, of which approximately 28% may be preventable. Patients who are sicker and have longer hospital stays experience more ADRs.16,17 Because elderly patients account for a disproportionate share of ADRs, these trends are relevant. Many, but not all, studies have revealed an association between old age and a greater risk for adverse events in hospital, community, and nursing home settings.2,18,19 Most studies examining the effect of age on ADRs have used a crude stratification of <65- and >65-year-old age groups. Analysis of hospital admissions suggests that 10% to 17% of acute geriatric admissions are related to ADRs.20-23 An additional complement is related to noncompliance, which also contributes to increased emergency room visits.20,24 The most recent outpatient survey estimated that 18% of elderly outpatients suffer ADRs.25 Correlates were the number of medical problems, number of medications, lower compliance, and presence of renal disease. Predictable ADRs are even more common (35%) in high-risk elderly outpatients (ie, those taking ³ 5 drugs daily).26 Many of these studies are limited because only a single outcome (hospitalization) was analyzed. Furthermore, studies that combine all drug exposures and that examine overall risk for drug toxicity provide little practical information about age-related risks of drug therapy.27 It has been consistently shown that the number of ADRs increases with the number of drugs taken. This increase is exponential rather than linear; thus an increase in the rate of ADRs with advancing age may be a simple consequence of increased exposure to multiple medications rather than an effect of aging on susceptibility per se. In fact, the upward spiral of ADRs with age tends to disappear when adjustments are made for the number of drugs taken.2,28 Thus, use of greater numbers of drugs, rather than age alone, is associated with an increased risk of ADRs. Equally important, the number of drugs that a patient is receiving is a marker for the number of coexisting diseases. Older person with more comorbidities and lower physical function scores use greater numbers of medications. The presence of multiple disorders, severe disease, and altered pharmacokinetics introduces additional elements contributing to ADRs in elderly patients. Additionally, the types of drug typically prescribed to the elderly (ie, digoxin, NSAIDs, diuretics, antihypertensives, antiarrhythmics, anticoagulants, etc) tend to increase risk. Thus, patient-specific physiologic and functional characteristics are probably more important than chronological age, which serves as an imprecise proxy for these patient-specific characteristics.Back to Top Pharmacokinetic and Pharmacodynamic Changes with Aging Most ADRs are dose-related and related to the number of concurrent medications. The study of ADRs in the elderly becomes more complex when one attempts to determine an age-appropriate dose for a particular medication. Many patients demonstrate an age-related decline in drug elimination. If lower doses are not routinely considered in such patients, blood concentrations of the drug will be too high for the clinical situation. In such cases, the increased rate of ADRs is a consequence of inappropriate prescribing. Pharmacokinetic Changes with Aging. These changes encompass the pharmacokinetic process of absorption, distribution, metabolism, and excretion. Absorption. Despite an age-related decrease in small intestinal surface area, increased gastric pH, decreased gastrointestinal tract blood flow, and increased gastric emptying time, absorption of food and drugs remains relatively unaltered in elderly patients.29,30 Changes in drug absorption tend to be clinically insignificant, but occasionally may be relevant when prodrugs are administered that undergo metabolic or other alteration prior to absorption. Drug interactions with laxatives, antacids, and agents that decrease gastric emptying are probably more important than any-age-related changes in gastrointestinal function. Distribution. Body composition changes with aging.29,30 Aging is characterized by decreased lean body mass, increased percentages of body weight represented as fat, and decreased total body water. The latter diminishes 10% to 15% between the ages of 20 and 80 years. The distribution of drug is altered in line with these known changes in body composition. Lipophilic drugs have an increased distribution volume, while drugs that are more water-soluble reflect the opposite and may be associated with higher blood concentrations. If a drug is highly protein bound, decreases in plasma proteins tend to elevate the free fraction, which is pharmacologically active. The consequence of this change depends on the distribution and elimination kinetics of the drug, being most significant for drugs with larger distribution volumes, slower elimination kinetics, and narrower margins of safety. Although albumin concentrations may be decreased in some elderly subjects, age-related changes in protein binding are usually not clinically important in drug therapy.31 Hepatic Metabolism. Drug metabolism is slower on average in the elderly. However, the ability of the aging liver to metabolize drugs does not decline in a similar way for all pharmacological agents, and the clearance of some drugs is largely unchanged.32-35 Most studies of aging and drug metabolism have involved simple pharmacokinetic investigations following the administration of a single drug dose. Because individuals vary greatly in rates of drug metabolism, largely as a result of genetic factors and environmental exposures, many individual elderly patients may have metabolic clearance rates within the range observed in younger subjects. In general, liver size is reduced 25% to 35% with aging.31 The main age-related change in the physiology of the liver is a substantial reduction in blood flow of about 40%.33 The hepatic content of various cytochrome P-450 isozymes (measured as mg protein/g liver tissue) is generally believed not to be reduced with aging; however, one study found that the concentrations of certain isozymes were approximately 30% lower in subjects >70 years old.34 Overall, the effect of these various changes is dependent on the mode of clearance for individual drugs, and a variable pattern emerges. For efficiently cleared, highly metabolized drugs (flow-dependent clearance), first-pass metabolism is reduced, resulting in higher plasma concentrations and reduced systemic clearance.33 The clearance of these drugs is a reflection of hepatic blood flow, and may be reduced up to 40%. Clearance of drugs with low extraction fractions is not significantly influenced by changes in blood flow, but rather is determined by a combination of liver mass (reduced), enzyme activity (relatively unchanged), and protein binding (variable). The clearance of these drugs is termed "capacity-limited." Their clearance may be reduced 25% to 30% or somewhat less, depending on the drug and relevant enzyme. Drugs subject to conjugation reactions (eg, glucuronidation, sulfation) appear to be least affected, and may not show any significant reduction in clearance. Renal Excretion. In general, aging is associated with decreased renal size and renal blood flow, leading to decreases in glomerular filtration rate. Decreases in tubular function parallel those in glomerular function. Based on cross-sectional studies, creatinine clearance decreases an average of about 8 ml/min/decade after age 30.36 Longitudinal analysis paints a different picture, however. Specific aging individuals suffer a much steeper decline, while some are normal and others demonstrate the average decline observed in cross-sectional studies. Up to one third of elderly patients have well-preserved renal function.37 Reduced systemic clearance in the elderly appears to be a typical finding for drugs that are eliminated unchanged by the kidney. Clinical implications depend on the relative contribution that renal elimination makes to total systemic clearance. Creatinine clearance, preferably measured or estimated from the Cockroft-Gault equation, can be used to adjust drug dosage. Pharmacodynamic Changes. In the elderly, the effects of similar drug concentrations at the site of action may be larger (opioid analgesics, benzodiazepines, warfarin, ACE inhibitors, calcium channel blockers, levodopa) or smaller (beta agonist bronchodilators, diuretics) than those in younger patients.30 Pharmacodynamic differences may be due to changes in drug-receptors, drug-receptor interactions, altered adaptive homeostatic responses, or in frail patients, organ pathology.Back to Top Prescribing medications is a complex task. Physicians learn how to prescribe in the "real-world" setting beginning with their residency training, and then are influenced by their peers, pharmaceutical company marketing, pharmaceutical benefit managers, and patient demand and expectation.38 Nevertheless, appropriate use of prescription drugs is often the most cost-effective intervention for elderly patients.38 However, inappropriate use carries large negative consequences. The economic costs attributable to medication-related problems in nursing homes, hospitals, and the community are enormous, totaling nearly $85 billion annually, with most of this referable to the outpatient community.39-41 Managing medication can be complex for older people who may take several drugs for multiple health problems. Complications may occur because of interactions between 2 drugs or between a drug and dietary supplement, or because of physiological and functional changes associated with aging or age-related diseases. Nonpharmacological factors also play a critical role in the safety and effectiveness of drug therapy in the elderly. Medication Assessment Tools to Determine Appropriateness There are three primary approaches to assessing the appropriateness of medication prescribing in the elderly. Explicit methods include "lists" of drugs to avoid and drug utilization review (or drug utilization evaluation). Implicit methods use criteria that are applied to individualized medication reviews that are patient-specific. These methods may have goals in addition to decreasing the number of medications used.42-43 Implicit methods are dependent on user knowledge and prescribing beliefs. Drug Lists. Consensus approaches using explicit criteria have been employed to develop lists of inappropriate drugs for patients ³ 65 years of age, inappropriate drug-disease combinations, and/or inappropriate drug-drug interactions. The most familiar is the "Beers criteria," first published in 1991.44 This list identified inappropriate medication use in nursing home residents; these explicit criteria were designed to use pharmacy data with minimal additional clinical data so that they could be applied to chart review or computerized data sets. The criteria embraced 19 medications or drug categories to be avoided and 11 criteria that described doses, frequencies, or duration of medication prescriptions that generally should not be exceeded in frail nursing home residents. The list was updated in 1997 to apply to older people in all care settings, adding a severity rating reflecting the likelihood of an adverse reaction, and incorporating clinical information on diagnoses when available.45 The updated criteria include 28 medications that should generally be avoided in the ambulatory elderly, doses or frequencies of administration that should generally not be exceeded, and 35 medications that should be avoided in older persons known to have any of several common conditions (drug-disease criteria). These criteria, or modifications thereof, have been used in epidemiological studies to estimate inappropriate prescribing in elderly patients in skilled nursing facilities, board and care facilities or hospitals, in homebound adults and patients within a Medicare HMO, and for prescriptions originating in outpatient clinics or from office-based physicians.46-50 Application of these criteria to community-based samples using population-based, nationally representative surveys found that 14% to 27% of community-dwelling older people used medications that should be avoided in the elderly.6,51,52 A recent follow-up study, which also relied on the 1996 National Medical Expenditure Panel Survey, analyzed a subset of drugs from the revised Beers list. Results of this study suggest that inappropriate medication use in elderly patients remains a serious problem; more than 20% of respondents aged 65 years or older received at least 1 potentially inappropriate medication.53 Critics of the Beers list note that certain drugs to be avoided (eg, propranolol, methyldopa, reserpine) may be appropriate for use in some patients. Issues concerning the use of NSAID are only minimally addressed by this list, which notes that indomethacin and phenylbutazone should be avoided. All NSAIDs carry risk in the elderly; the critical factor is usually based on the underlying medical condition and use of higher doses, rather than specific agents per se. Furthermore, this method evaluates specific medications or mediation classes, without addressing the complexity and appropriateness of the entire medication regimen. The prescribing of appropriate drugs in an inappropriate fashion accounts for a significant proportion of problematic prescribing in the elderly. A similar approach was used to develop another list based on explicit criteria.54 This consensus process identified 38 high-risk prescribing practices in the elderly, grouped among cardiovascular, psychotropic, analgesic, and miscellaneous agents in the context of drug-drug and drug-disease interactions. Inappropriate practices were categorized as generally contraindicated drugs, clinically important drug-drug interactions, and drug-disease interactions. They included practices that met 1 of the following 3 criteria: (1) the prescription introduces a substantial and clinically significant increase in the risk of a serious adverse event; (2) equally or more effective therapy and less risky alternative therapy is available for most patients; and (3) the practice is likely to occur often enough that a change in practice could decrease morbidity in older people. This list identified 38 problematic or inappropriate prescribing practices, including 18 contraindicated drugs/drug classes, 16 drug-disease interactions, and 4 drug-drug interactions. There was only partial overlap with the Beer’s criteria. Objective, explicit, evidence-based criteria also have been proposed to identify potential prescribing problems with benzodiazepines, corticosteroids in chronic obstructive pulmonary disease, and stroke Drug Utilization Reviews. Drug utilization review (DUR) is the "evaluation of drug use in a given health care environment against predetermined criteria and standards to assess the appropriateness of drug therapy."56 Criteria are explicit, predetermined statements about appropriate drug use. They are a mechanism for alerting prescribers and pharmacists to the likelihood that a prescription is inappropriate. Without measuring outcomes, criteria cannot determine whether adverse outcomes have occurred; they can only determine that they are most likely to occur. Standards are statements of expected levels of performance that include, when appropriate, the range of acceptable variation from criteria. If therapy is determined to be inappropriate, interventions may be needed with specific patients and/or providers to optimize drug therapy. Drug utilization review programs are customized (in terms of scope and data used) to fit the environment in which they operate. Programs are administered to monitor drug therapy provided to patients in hospitals, nursing homes, and other residential environments, and on an outpatient basis. The latter include programs administered by the government (Medicaid), private third-party insurance programs, pharmaceutical benefit managers, and other managed care organizations. The timing of DUR in relation to dispensing determines the amount and type of data reviewed:
When conducted in the hospital setting, the term drug use evaluation (DUE) is commonly employed. It traditionally has been treated as the gold standard for assessing appropriateness of a drug in the institutional setting, particularly hospitals. Typically, DUE is drug-specific and uses explicit criteria to assess indication, critical process indicators, complications, and outcomes.57 Use of a consensus panel may improve content validity. However, questions remain about DUE validation. Implicit Methods. As the concept of pharmaceutical care was advanced, methods employing implicit criteria or algorithms were developed, and assessment tools that combined structured review criteria and implicit judgment also appeared.58-61 Typically these assessments involve a clinician who utilizes information readily available in a patient’s medical record and evidence from the literature to make judgments. Implicit reviews focus on the appropriateness of a patient’s entire medication regimen rather than on a single drug or drug class, and combines the patient’s medical history and the clinician’s judgment and knowledge.62 Lipton et al60,63 identified 6 scaled domains to measure inappropriate prescribing, including lack of indication, improper schedule, inadequate dosage, potential drug interactions, therapeutic duplication, and allergy. Application of these criteria found that 22% of older outpatients have serious problems with 1 or more of these categories. A "Medication Appropriateness Index" (MAI) based on 10 criteria (indication, effectiveness, dosage, practical directions, correct directions, drug-drug interactions, drug disease interactions, duration, duplication, and cost) also has been developed and tested in male veteran inpatients and outpatients.61 Higher MAI scores are associated with adverse health outcomes.64 This measure also appears to be a reliable instrument for evaluating medication appropriateness in a non-Veterans Administration, ambulatory, elderly population.65 In one study, prescribing for elderly outpatients taking multiple medications was judged substantially appropriate using this measure.66 Prescribing dimensions with the most opportunity for improvement were more exact and practical directions and cost. Drugs at high risk for adverse effects were prescribed more appropriately than those at low risk.Back to Top Suboptimal prescribing may encompass overuse or polypharmacy, inappropriate prescribing, or underutilization. Overuse or Polypharmacy. Polypharmacy is the administration of multiple medications.. While polypharmacy is often viewed as a pejorative term, in many cases the use of multiple medications is justified because of concurrent or severe illness. When the use of multiple medications is not justified, or is inappropriate, the pattern represents overuse. Physicians contribute to overuse by prescribing a drug without a proper indication or acceding to patient expectations for a prescription. Furthermore, prescribing additional drugs to treat drug-induced symptoms that are misinterpreted as a new disease sign or symptom can lead to prescribing cascades. Patients contribute by not acknowledging all medications (including OTC medications and dietary supplements) they are receiving or by receiving medications from more than one physician. Polypharmacy is problematic for older persons because it is the greatest risk factor for ADRs, drug interactions, reduced compliance, and increased emergency room visits, hospitalizations, and nursing home admissions. It contributes to the development of several "geriatric syndromes" such as cognitive impairment, delirium, falls and hip fractures, urinary incontinence, and diminished functional status, and it increases health care costs. Inappropriate Use. Inappropriate use is the prescribing of a medication that has more potential risk than potential benefit, or prescribing that does not agree with accepted medical standards. Such practices contribute to increased hospital admissions in the elderly.67,68 Categories of inappropriate use include improper drug selection, use of a drug without indication (including continuing the use of a drug after the indication is no longer present, choosing an appropriate drug but the wrong dose (too low or too high), or any of several other elements of the drug treatment plan. Underutilization. Underutilization is the omission of drug therapy that is indicated for the treatment or prevention of a disease or condition. Although most attention has been focused on the risks of inappropriate or excessive prescribing in the elderly, concern also exists about the consequences of underprescribing of potentially beneficial therapies to patients ³ 65 years of age. Application of explicit criteria has revealed underutilization in the use of secondary prevention (beta-blocker, aspirin, lipid-lowering agents) after myocardial infarction, treatment of hypertension, use of ACE inhibitors in patients with congestive heart failure, use of estrogen replacement therapy in postmenopausal women at risk for osteoporosis, treatment of cancer pain, and use of warfarin in older patients with atrial fibrillation and contraindications to treatment.69-77 In one study, more than 50% of ambulatory older patients had one or more necessary drug therapies omitted by their physicians.63 Several factors operate to limit the use of beneficial drug therapy in geriatric patients. Some physicians do not view secondary prevention as a priority for patients of advanced age; rather the focus is on immediate improvement in quality of life. For patients with chronic diseases, other unrelated diseases may be left untreated, reflecting a viewpoint that treatment of the patient’s primary problem is sufficient. Finally, financial barriers may prevent access to therapy; more than 40% of all Medicare enrollees do not have coverage for outpatient drugs.78 Methods to Improve Suboptimal Prescribing. Several methods have been evaluated in an attempt to improve suboptimal prescribing. Investigators from a pharmaceutical benefits management group, using a population-based cohort design, evaluated provider prescribing through a computerized on-line DUR database that used explicit criteria (adapted Beers list) to identify potentially inappropriate drug use in community-dwelling elderly people.79 Computer alerts triggered telephone calls to physicians by pharmacists with training in geriatrics. A 24% rate of change to more appropriate prescribing occurred. The use of prescription claims data offers advantages in drug surveillance, including the ability to document all health services use without recall bias or incomplete drug history. Other methods include hospital formularies and other restrictions such as requirements for prior authorization or mandatory advance approval; use of opinion leaders for physician education; academic detailing; and targeted pharmacist activities, including participation in a multidisciplinary team approach.80-83Back to Top Appropriate Prescribing for the Elderly The principal clinical concerns in geriatric pharmacotherapy are efficacy, safety, appropriate drug and dose, the complexity of the treatment regimen, cost, and patient compliance. There is no simple rule for prescribing drugs for the elderly. Variables in determination of dose and compliance make the development of specific recommendations for drug prescribing in the elderly very difficult. Dosage Determination. The common recommendation in prescribing for geriatric patients is to "start low and go slow" and sometimes to say "no." With respect to dosage, low body weight, in addition to advanced age, is a major risk factor for overmedication. Physicians must recognize the need to reduce drug doses for their low-weight elderly patients. In one landmark study, patients (mean age 72 years) weighing 50 kg or less received mg/kg doses 31% to 45% higher than the group mean and 70% to 88% higher than patients weighing more than 90 kg.84 However, wide interindividual variation exists in the rate of age-related changes in physiological parameters that affect drug disposition; the hallmark is decreased homogeneity. Chronological age and biological age are not synonymous. Thus, precise predictions for individual elderly persons are difficult to make. The clinical status of each patient (including factors such as nutrition and hydration, cardiac output, intrinsic renal and hepatic function) must be considered in addition to the effects of aging. On the other hand, certain factors such as changes in renal function are readily quantifiable by use of the Cockcroft-Gault equation, and this approach should be employed routinely in clinical practice. There is a relative lack of specific dosage recommendations in FDA-approved product labeling for geriatric patients, particularly among older subsets. The paucity of clinical trials in geriatric subjects, particularly those ³ 75 years of age, is usually blamed. However, trials that do not permit translation of study results to clinical practice are of little value to the clinician and to the patients being treated. The marked heterogeneity of the elderly population creates problems in research design. A major concern in studies of the elderly is the selection of subjects. The elderly population represents a continuum from "fit" to "frail"; however, most studies in aged individuals include only the "fit." These subjects are probably more similar physiologically and pharmacokinetically to younger people than to their chronological peers. The current pharmacokinetic database comprises mostly studies of healthy individuals aged 60 to 75 years. Few data are available to support (or refute) extrapolation of the current pharmacokinetic database to the (sick) patient population in whom the drug will be used. Similarly, the most straightforward study, single-dose exposure, may provide an incomplete understanding of pharmacokinetics during multiple-dose drug administration. Although it is appropriate for physicians to feel hesitant about using lower drug doses without proof or product labeling stating their effectiveness, a large number of studies involving lower doses of several commonly used drugs have been conducted (Table 2).85 Compliance. The majority of older persons are responsible for taking their own medications. Compliance is the extent to which a person’s behaviors coincide with medical advice. Physician judgment is a poor predictor of who is taking medications according to the prescribed schedule.86 Achieving optimal compliance involves a process of medication selection, choice of the initial dose and dose interval and subsequent adjustments, assessment of outcome, utilization of information from the patient and family or other caretaker, reexamination of the need for medications, and the attempt to avoid clinically significant drug-disease and drug-drug interactions. Many theories about compliance have been elaborated and many interventions to foster compliance have been evaluated. Drug compliance requires a patient to perform at varying cognitive levels and the patient’s health literacy plays a critical role in communicating with the patient and evaluating responses. Discussion of these theories and elements is beyond the scope of this report. It is worth noting that there has been some interest in developing tools to assess the capacity of older patients to comply with medication regimens.87,88 Failure to comply with drug-prescribing recommendations is not a problem unique to the elderly; however, some causes of noncompliance are more common in the elderly or somewhat different compared with factors involved in younger age groups. As previously noted, a higher percentage of the elderly take multiple drugs. Use of 3 or more drugs daily places elderly patients at risk of poor compliance, as does living alone. The elderly may exhibit unintentional noncompliance due to forgetfulness or confusion or impaired physical function, especially decreased vision. Hospital admissions for drug-related illness due to unintentional noncompliance are approximately double those seen in the general population.20 Elderly patients also may exhibit intentional noncompliance because of side effects or financial barriers. Prescription noncompliance also contributes to increased emergency room visits.24 Some patients use more drug than prescribed in the mistaken belief that this will speed recovery. As many as 10% of elderly people take drugs prescribed for others, and more than 20% may take drugs not currently prescribed by a physician. Techniques for improving medication compliance in the elderly begin with communication between the physician and the patient. Use of charts and written instructions to augment verbal communication can be helpful. Timing of medication administration should be matched to the patient’s daily schedule. Mechanical aids and color-coding for packaging and organizing pill counts can be very helpful. Physicians may need to specify that medications should not be dispensed in safety-cap containers. Role of the Pharmacist As previously discussed, clinical pharmacists provide valuable services in drug utilization reviews, particularly with regard to the use of implicit methods.58-66 Enhanced pharmacist participation also has shown beneficial effects in several other domains of geriatric pharmacotherapy, including decreasing the rate of preventable ADRs, improving compliance, simplifying drug regimens, and producing direct cost savings.65, 89-92 Recently, a position paper on pharmacist scope of practice released by the American College of Physicians-American Society of Internal Medicine supported increased pharmacist involvement in patient education and hospital rounds in order to improve patient safety and reduce medical errors.93Back to Top General Recommendations for Prescribing for the Elderly Many individuals and organizations have recommendations for improving prescribing for the elderly. A summary of various suggestions is given here: Some General Principles for Improving Geriatric Prescribing Periodically review the medication regimen of all elderly patients and avoid polypharmacy. Discontinue medications when there is no ongoing need, eliminate medications with no therapeutic benefit, and substitute a safer medication if available. Avoid treating an adverse drug reaction (ADR) with another drug. A prescribing cascade begins when an ADR is misinterpreted as a new medical condition. Know the pharmacology of the drug(s) being prescribed. Carefully consider the side effect profile of each medication; and identify potential risk factors in order to avoid ADRs and drug interactions. Select carefully within a drug class to reduce the risk of adverse effects.If there is a question about drug dosage, start with smaller doses and increase gradually. For drugs or their active metabolites eliminated predominantly by the kidney, use a formula or nomogram to approximate age-related changes in renal function and adjust dosages accordingly. Do not confuse low-dose therapy with inappropriate suboptimal dosage. Titrate drug dosage based on the patient’s response and establish reasonable therapeutic endpoints. Simplify regimen and help to ensure compliance by paying attention to impaired intellectual function, diminished hearing, and poor vision when instructing patients. Provide patients with clearinstructions, both verbally and in writing in terms that they will understand. If the patient is being seen by home health nurses and aides, communicate directly with them to help monitor for ADRs. Develop an awareness of the cost of medications. Evidence of increased drug use and increased ADRs with aging, along with documentation of inappropriate prescribing practices for older patients, indicate that substantial opportunities for improvement still exist with regard to geriatric pharmacotherapy. A broader view of prescribing for seniors recognizes that problems occur from both over- and underutilization, as well as inappropriate prescribing of drugs. Assessing the quality of prescribing is considerably more complex than simply counting the number of different medications that an elderly patient is receiving. A number of medication assessment tools are available to clinicians for the purpose of evaluating medication regimens. Most of these help identify medication-related problems, but do not address the problem of underutilization. Underuse of beneficial drug therapy by elderly patients is associated with increased morbidity and mortality, and reduced quality of life. Efforts to address this issue must focus on educating health care providers, improving adherence to prescribed drug regimens by older patients, and reducing the financial barriers to access to essential medications. Failure to consider these efforts can limit the success of any quality improvement effort, which must emphasize the role of the primary care physician. Despite specific FDA guidelines, a lack of knowledge persists about which aspects of aging are the most important determinants of drug efficacy and toxicity in individual patients—body composition, sex, renal function, receptor sensitivity, liver function, comorbidity, or multiple drugs. These guidelines are unlikely to help immediately with the difficult problem of understanding the effects of new medications in frail elderly patients with multiple chronic illnesses who take multiple medications. Pharmacokinetic studies in healthy elderly individuals may provide little useful information beyond that obtained in studies undertaken in healthy young adults. Only after drugs leave the trial setting and are used in sicker patients do their true risks become apparent. Nevertheless, increased participation of older subjects in clinical trials, enhanced post-marketing studies of new drugs among subgroups of the elderly who were not represented in premarketing studies, and use of systematic reviews of clinical trial data would improve the quality of information available. The latter approach would be aided by standardized reporting of trial data by age to provide a basis for meta-analysis. Conventional wisdom supports the use of lower doses when prescribing drugs for older patients. The degree to which the dose is reduced depends on the medication and the clinical situation, but use of low doses should not be confused with the need to reach the target therapeutic range. Except for drugs eliminated by conjugation, it is reasonable to anticipate a 30% to 40% decrease in dosage for drugs eliminated by the liver. With regard to ADRs, other factors are more important than age per se, including the number of medications taken, the kind of medications taken, and comorbidity of illness and burden of disease. Concerns persist about the training of physicians for their lifelong role as prescribers.39 The overwhelming proportion of drug-induced illness in the elderly stems from prescribing of the wrong drug (if the drug is needed at all) or the wrong dose in an elderly patient. Regardless of the levels of funding for geriatric research and health care, there are insufficient number of trained scientists (gerontologists) and caregivers (geriatricians) to conduct the research; deliver services to older persons; and teach generalists, nurses, and other health care providers how to treat the elderly wisely (about 1% of total US physician population are certified geriatricians). A need remains to conduct research, provide care in difficult cases, and teach others. Ultimately, the assessment of prescribing quality "should be woven into the fabric of the delivery system, performed on an ongoing basis, and [be] tightly linked to educational strategies to improve care."94Back to Top RECOMMENDATIONS (Adopted AMA Policy and Directives) The folowing statements, recommended by the Council on Scientific Affairs, were adopted by the AMA House of Delegates as AMA directives and policy at the 2002 AMA Annual meeting:
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Table 1. Recommendations of the Surgeon General’s Medication Working Group (1988) Education and training 1. More training and continuing medical education courses should be provided that emphasize:
2. Social service providers, home caregivers, family members, and older adults should be:
3. The role of pharmacists in management of and education about geriatric medication should be expanded. 4. Sites for geriatric-specific prescribing information in all practice settings should be identified. Service
Research
Policy
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Table 2. Comparison of the Initial Dosesa Recommended in the FDA-Approved Product
Labeling versus Lower Effective Doses Reported in the Medical Literature85
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Drug |
Recommended Initial Dose |
Effective Lower Dose |
|
Acebutolol hydrochloride |
400 |
200 |
|
Amitriptyline hydrochloride |
50-75 |
10-25 |
|
Amiodipine besylate |
5 |
2.5 |
|
Atenolol |
50 |
25 |
|
Atorvastatin calcium |
10 |
2.5 and 5 |
|
Bisoprolol fumarate |
5 |
2.5b |
|
Bupropion hydrochloride |
100 BID |
50 BID |
|
Celecoxib |
100 BID |
50 BID |
|
Cerivastatin sodium |
0.4 |
0.2 or 0.3 |
|
Chlorthalidone |
15 |
12.5 |
|
Cimetidine hydrochloride |
800 HS |
400 HS |
|
Estrogens, conjugatedc |
0.625 |
0.3 |
|
Diclofenac sodium |
50 BID-QID |
25 TID |
|
Doxepin hydrochloride |
75 |
10, 25, or 50 |
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Ethacrynic acid |
50 |
25 |
|
Famotidine |
20 BID or 40 QD or BID |
10 BID or 20 QD |
|
Felodipine |
5 |
2.5 |
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Fexofenadine hydrochloride |
60 BID |
20 TID or 40 BID |
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Fluoxetine hydrochloride |
20 |
2.5, 5, or 10 |
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Flurazepam hydrochloride |
30 QHS |
15 QHS |
|
Furosemide |
80 |
40 |
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Hydrochlorothiazide |
25 |
12.5 |
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Ibuprofen |
400 TID-QID |
200 TID |
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Imipramine hydrochloride |
75 |
10-25 |
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Lisinopril |
10 |
5 |
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Losartan potassium |
50 |
25 |
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Lovastatin |
20 |
10 |
|
Metoprolol tartrate |
50-100 |
50 |
|
Misoprostol |
200 µg |
50 or 100 µg QID |
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Nefazodone hydrochloride |
100 BID |
50 QD or BID |
|
Nizatidine |
150 BID or 300 HS |
25 BID or 100 HS |
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Nortriptyline hydrochloride |
50-75 |
10 or 25 |
|
Omeprazole |
20 |
10 |
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Ondansetron hydrochloride |
8 BID |
1-4 TID |
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Penbutolol sulfate |
20 |
10 |
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Pravastatin sodium |
10-20 |
5-10 |
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Propranolol hydrochloride |
80 |
40 |
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Ramipril |
2.5 |
1.25 |
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Ranitidine hydrochloride |
150 BID or 300 HS |
100 BID |
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Sertraline hydrochloride |
50 |
25 once daily |
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Simvastatin |
10-20 |
2.5, 5, or 10 |
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Spironolactone |
50-100 |
25 |
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Torsemide |
10 |
5 |
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Trazodone hydrochloride |
150 |
25-100 |
|
Triamterene |
100 BID |
25-100 QD |
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Venlafaxine hydrochloride |
75 |
37.5 or 50 (in divided doses) |
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Verapamil hydrochloride |
120-180 |
90 |
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Zolpidem tartrate |
10 mg vs 5 mg |
7.5 HS |
aDose values are given as milligrams per day unless otherwise indicated. BID, 2 times daily; HS, at bedtime; QID, 4 times daily; TID, 3 times daily; QD, daily; QHS, every night; and XL,extended release.
bProduct labeling states the "usual" initial dose is 5mg/d, but notes that 2.5 mg/d may be
sufficient for "some patients." The sixth report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure recommends 2.5 mg/d initially for all patients.
cFor vasomotor symptoms
Resolution 503, introduced by the Medical Student Section and referred to the Board of Trustees at the 2000 Interim AMA Meeting, asked:
That the AMA, in conjunction with the American Geriatrics Society and appropriate specialty societies, study ways to improve our understanding of geriatric pharmacology and to educate our physicians on the special pharmacological needs of the geriatric population; and
That the AMA, in conjunction with the American Geriatrics Society and appropriate specialty societies, promote the comprehensive inclusion of senior-specific criteria in drug utilization reviews, especially with regards to age-related adverse drug reactions and appropriate dosing.Back to Top
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