Appropriate Approach to Prescribing: Introduction
Prescribing for older patients offers special challenges. Older people take about three times as many prescription medications as do younger people, mainly because of an increased prevalence of chronic medical conditions among the older patient population. Taking several drugs together substantially increases the risk of drug interactions and adverse events. Many medications need to be used with special caution because of age-related changes in pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (see Chapter 8). For some drugs, an increase in the volume of distribution (e.g., diazepam) or a reduction in drug clearance (e.g., lithium) may lead to higher plasma concentrations in older patients than it does in younger patients. Pharmacodynamic changes with aging may result in an increased sensitivity to the effects of certain drugs, such as opioids, for any given plasma concentration. The pharmacokinetic and pharmacodynamic changes with aging are discussed in Chapter 8.
While a physician can usually do little to alter the characteristics of individual older patients to affect the kinetics or dynamics of drugs, the decision whether to prescribe any drug, the choice of drug, and the manner in which it is to be used (e.g., dose and duration of therapy) are all factors that are under control of the prescriber. This chapter discusses ways to optimize prescribing of drug therapy for older adults.
Epidemiology of Drug Therapy
Writing a prescription is the most frequently employed medical intervention. Yet, creating optimal drug regimens that meet the complex needs of older persons requires thought and careful planning. Multiple factors contribute to inappropriate drug prescribing, including lack of adequate training of doctors in safe prescribing behavior and in prescribing for geriatric patients. Further, a lack of a routine use of safe medication prescribing behaviors such as checking drug allergies, double checking drug doses, adjusting doses for renal impairment, and potential drug–drug interactions also contribute to prescribing errors. Avoidable adverse drug events (ADEs) are the most serious consequences of inappropriate drug prescribing. The possibility of an ADE should always be borne in mind when evaluating an elderly individual. A maxim from one wise geriatrician recommends: “In evaluating virtually any symptom in an older patient, the possibility of an ADE should be considered in the differential diagnosis.” Advanced age, frailty, and increased drug utilization are all factors that contribute to an individual patient’s risk for developing a drug-related problem. In the ambulatory setting, 25% of patients may have ADEs. When an ADE is identified in the ambulatory setting between 11% and approximately 25% are considered to be preventable. In the nursing home setting, the incidence is higher and approaches 10 ADEs per 100 resident-months, of which over half were preventable. These estimates are probably low because preventable ADEs were strictly defined and assumed that, in many cases, the prescription of the offending drug was indicated and the ADE was therefore not preventable. As many as 28% of hospital admissions among older patients result from drug-related problems. Up to 70% of these drug-related admissions are attributed to adverse drug reactions. Perhaps the most compelling explanation for the prevalence of ADE in older patients is that we lack methods for determining the harms associated with the multiple medications consumed simultaneously.
A random sample of 2590 noninstitutionalized older adults in the United States during the years 1998 and 1999 provides information on the use of prescription and over-the-counter medications in the community. This survey demonstrated that use of all medications (prescriptions, over-the-counter drugs, vitamins/minerals, and herbals/supplements) (Figure 24-1) and the use of prescribed drug therapies (Figure 24-2) increases dramatically with advancing age. The highest prevalence of medication use was among women aged 65 years and older. Among these women, 12% took 10 or more medications and 23% took at least five prescribed drug therapies. The use of a larger number of drugs is associated with an increased likelihood of inappropriate prescribing, ADEs, and risk for geriatric syndromes including cognitive impairment, falls, hip fractures, and urinary incontinence. The widespread use of over-the-counter drug therapies indicates the importance of routinely inquiring about their use when evaluating a drug therapy regimen.
Herbal medicines are frequently used by older adults; physicians often do not question patients about such use. An estimated 14% of the U.S. population takes an herbal medicine or supplement such as ginseng, ginkgo biloba extract, and glucosamine. The use has increased from among adults who are 50 years of age or older, from 28% in 1991 to 39% in 1997. In one survey, almost 75% did not inform their physician that they were using unconventional treatments including herbal medicines. Herbal medicines may interact with prescribed drug therapies leading to adverse events, underscoring the importance of routinely questioning patients about their use of these unconventional therapies. Examples of herbal–drug therapy interactions include warfarin in combination with ginkgo biloba extract leading to an increased risk of bleeding and serotonin-reuptake inhibitors in combination with St. John’s Wort leading to serotonin syndrome in older adults.
Measuring the Quality of Drug Prescribing in Older Persons
Various criteria have been developed by expert panels in Canada and in the United States to assess the quality of medication use in elderly patient populations. The most widely used criteria employed for the assessment of inappropriate prescribing are based on the Beers criteria. These criteria were developed in 1991 by a consensus panel of experts in geriatric medicine, geriatric psychiatry, and pharmacology to evaluate inappropriate prescribing in nursing home residents. This expert group identified a list of medications considered inappropriate for older patients, either because they are ineffective or because they pose a high risk for adverse events. The list included long-elimination half-life benzodiazepines (e.g., diazepam) and hypoglycemic agents with long half-lives (chlorpropamide), antidepressants with strong anticholinergic properties (e.g., amitriptyline), and ineffective dementia treatments (e.g., cyclandelate). The Beers criteria were revised in 1997 and again in 2003 to make them more relevant to current prescribing issues and to generalize them beyond the nursing home setting. The 1997 revision recategorized the 33 medications deemed inappropriate according to the Beers criteria into three groups: (1) drugs that should always be avoided (e.g., barbiturates, chlorpropamide); (2) drugs that are rarely appropriate (e.g., diazepam, propoxyphene); and (3) drugs with some indications, but that are often misused (e.g., oxybutynin, diphenhydramine). The 2003 reorganization acknowledged that precise information to evaluate appropriateness may be lacking; two categories were generated: (1) medications or medications classes that should generally be avoided in persons 65 years or older because they are either ineffective or they pose unnecessarily high risk for older persons and a safer alternative is available and (2) medications that should not be used in older persons known to have specific medical conditions.
Use of drug therapies considered inappropriate according to the Beers criteria has been identified as an ongoing problem among community-dwelling older adults. The prevalence of inappropriate drug use remained steady between 1995 and 2000. Using the subset of the 20 drug therapies from the original Beers criteria that should be entirely avoided, 23.5% of community-dwelling older adults in the United States, as identified using the 1987 National Medical Expenditure Survey, were found to be taking one or more of the inappropriate medications. Three percent used at least one of the 11 drug therapies that the panel determined should always be avoided by older adults. Data from other surveys showed that the risk of hospitalization, emergency department visits, and death were greater for nursing home patients who had been prescribed potentially inappropriate medications.
The Health Care Financing Administration (now called The Centers for Medicare and Medicaid Services) expert consensus panel drug utilization review criteria have also been used to evaluate inappropriate prescribing in community-dwelling older adults. These criteria target eight prescription drug classes (i.e., digoxin, calcium channel-blockers, angiotensin-converting enzyme (ACE) inhibitors, histamine-2 receptor antagonists, nonsteroidal antiinflammatory drugs (NSAIDs), benzodiazepines, antipsychotics, and antidepressants) and focus on four types of prescribing problems: (1) use of an inappropriate dosage; (2) duplication of therapies; (3) potential for drug–drug interactions; and (4) inappropriate duration of therapy. Based on the criteria, almost 20% of 2508 community-dwelling older adults were found to be using one or more medications inappropriately. NSAIDs and benzodiazepines were the drug classes identified with the most frequent potential problems.
Unfortunately, the vast majority of medications that are commonly implicated in preventable ADEs are not identified by these widely used “bad drug” lists. Inappropriate prescribing is often more subtle, more pervasive, and often unrecognized. “Good drugs” prescribed in an inappropriate manner may be far more common and problematic. Very few drugs that cause difficulty for older adults are inherently bad. To address these concerns, a more comprehensive approach to evaluating the quality of pharmacologic care for older adults was developed by the Assessing Care of Vulnerable Elders (ACOVE) project. These include 12 quality indicators for appropriate medication use identified by Knight and Avorn. Table 24-1 describes each of the 12 indicators and summarizes the rationale for its need. These indicators start with the need to document the indication for a new drug therapy, to educate patients on the benefits and risks associated with the use of a new therapy, the need to maintain current medication lists in patient medical records, the importance of documenting response to therapy, and the need for a periodic review of drug therapies. In addition, these indicators specify seven drug therapies that either should not be prescribed for older adults (i.e., hypoglycemic agent chlorpropamide, drugs with strong anticholinergic properties, barbituates, and meperidine) or that warrant careful monitoring after they have been initiated (i.e., warfarin, diuretic, and ACE inhibitor therapy).
INDICATOR TITLE | DESCRIPTION | RATIONALE |
|---|---|---|
Indication | When prescribing a new drug, the therapy should have a clearly defined indication documented in the medical record. | The medication may have been prescribed for an indication that was unclear or transient. |
Patient education | When prescribing a new drug, the patient or caregiver should be educated about the optimal use of the therapy and the anticipated adverse events. | Education may improve adherence, clinical outcomes, and alert patients or caregivers to potential adverse events. |
Medication list | Medical records (outpatient or hospital) should contain a current medication list. | Allows identification and elimination of duplicate therapies, corrects drug interactions, and streamlines the drug regimen to improve adherence. |
Response to therapy | Every new drug prescribed on an ongoing basis (e.g., for a chronic condition) should have documentation of response of therapy within 6 months. | Provides a rationale for continuation of the therapy if effective, or change or discontinuation if ineffective. |
Periodic drug review | Annual drug regimen review. | Provides an opportunity to discontinue unnecessary therapy or to add needed drug therapies. |
Monitoring warfarin therapy | When warfarin is prescribed, international normalized ratio (INR) should be evaluated within 4 days and at least every 6 weeks. | Older adults are at high risk for drug toxicity that can be identified earlier if there is close monitoring for agents with a narrow therapeutic range. |
Monitoring diuretic therapy | When a thiazide or loop diuretic therapy is prescribed, electrolytes should be checked within 1 week after initiation and at least annually. | Risk of hypokalemia because of diuretic therapy. |
Avoid use of chlorpropamide as a hypoglycemic agent | When prescribing an oral hypoglycemic agent, chlorpropamide should not be used. | This therapy has a prolonged half-life that can result in serious hypoglycemia and is more likely than other agents to cause the syndrome of inappropriate secretion of antidiuretic hormone. |
Avoid drugs with strong anticholinergic properties | Do not prescribe drug therapies with a strong anticholinergic effect if alternative therapies are available. | These therapies are associated with adverse events such as confusion, urinary retention, constipation, and hypotension. |
Avoid barbituates | If older adult does require the therapy for control of seizures, do not use barbiturates. | These therapies are potent central nervous system depressants, have a low therapeutic index, are highly addictive, cause drug interactions, and are associated with an increased risk for falls and hip fracture. |
Avoid meperidine as an opioid analgesic | When analgesia is required, avoid use of meperidine. | This therapy is associated with an increased risk for delirium and may be associated with the development of seizures. |
Monitor renal function and potassium in patients prescribed angiotensin-converting enzyme inhibitors | If angiotensin-converting enzyme inhibitor therapy is initiated, potassium and creatinine levels should be monitored with 1 week of initiation of therapy. | Monitoring may prevent the development of renal insufficiency and hyperkalemia. |
Underprescribing of potentially useful medications is at least as problematic as overprescribing of potentially harmful medications. Using a subset of ACOVE quality indicators and a sample of 372 vulnerable older adults in two managed care organizations, investigators determined the proportion of patients who met criteria for underprescribing potentially useful medications and overprescribing potentially harmful medications. Of nine quality indicators measuring the overprescribing of harmful medications, eight had a pass rate of 90% or greater. Of 17 quality indicators measuring the underprescribing of useful medications, only 1 had a pass rate of 90% or greater; eight had a pass rate of less than 60%. In another study, investigators found coexistence of both the inappropriate use of harmful medications and the under use of beneficial medications in 42% of study patients; 13% had neither. The complexity of safe and effective prescribing for older adults with multiple chronic conditions makes the determination of appropriate prescribing difficult to assess. Defining over- and underprescribing outside the context of individual measures of disease burden, total medication use, and preferences may be misleading and fraught with unintended consequences. These estimates of over- and underprescribing should, therefore, be interpreted cautiously.
Prescribing Cascades
A particularly concerning aspect of suboptimal medication use in older adults relates to the occurrence of prescribing cascades. A prescribing cascade begins when an ADE is misinterpreted as a new medical condition. An additional drug therapy is prescribed, and the patient is placed at risk for the development of additional ADEs relating to this potentially unnecessary treatment (Figure 24-3). Prescribing cascades and other risks associated with drug therapy are particularly important for older adults with multiple chronic diseases who are likely to be prescribed multiple drug therapies. Selected examples of prescribing cascades are described below.
Among 95 new cases of Parkinson’s disease from community-dwelling older adults referred to a geriatric medicine department in the United Kingdom, more than half were found to have drug-induced Parkinsonism. Conventional antipsychotic medications such as haloperidol, prochlorperazine, and thioridazine were among the major drug therapies implicated.
The association between antipsychotic drug exposure and subsequent treatment of Parkinsonism was identified among 3512 adults aged 65 to 99 years who were enrolled in a Medicaid program and initiated on a drug therapy for the treatment of Parkinsonian symptoms. Patients dispensed a antipsychotic therapy in the 90 days prior to the initiation of anti-Parkinson’s therapy were more than five times more likely to begin anti-Parkinson’s therapy relative to control patients who were not dispensed antipsychotic therapy. Furthermore, a dose–response relationship was demonstrated.
Antipsychotic therapy is widely used in older adults for the management of behavioral problems associated with dementia. Antidopaminergic-related adverse effects associated with these agents have long been recognized, including the development of extrapyramidal signs and symptoms. This drug-related symptom may be potentially misdiagnosed as a new medical condition (i.e., Parkinson’s disease). A recent study has demonstrated that even the newer “atypical” antipsychotics can be associated with Parkinsonism in a dose-related fashion. Patients who are placed on anti-Parkinsonian therapy then become vulnerable to the adverse events associated with this new therapy, including hypotension and delirium. A better approach is to discontinue or reduce the dose of the antipsychotic therapy. If an antipsychotic is deemed essential, it is prudent to select a therapy with a more favorable adverse effect profile and to use this therapy at the lowest feasible dose. Even newer agents have adverse effects at higher doses.
Drug-induced Parkinsonism has also been reported with other drug therapies, including metoclopramide. A case–control study of adults aged 65 years and older in the New Jersey Medicaid Program demonstrated that metoclopramide users were three times more likely to begin drug treatment for Parkinson’s disease as compared with nonusers. Risk increased with increasing daily metoclopramide dose such that the odds ratio was 1.19 for up to 10 mg/day, 3.33 for 10 to 20 mg/day, and 5.25 for >20 mg/day. Thus, drug-induced Parkinsonism may lead to the initiation of anti-Parkinson drug therapy. Such drug-induced symptoms in an older person can be misinterpreted as indicating the presence of a new disease or be attributed to the aging process rather than to the drug therapy. This misinterpretation is particularly likely when the symptoms are indistinguishable from an illness, such as Parkinson’s disease that is seen in greater frequency in older persons.
Cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine) are often prescribed to manage the symptoms of Alzheimer’s disease and related dementias. Through their effects on the autonomic nervous system, cholinesterase inhibitors can sometimes precipitate urge urinary incontinence. However, new-onset or worsening urge incontinence is also commonly seen as part of the natural history of dementia. Thus, clinicians may misinterpret incontinence in patients with dementia as an unavoidable progression of their underlying disease, when it may in fact represent a potentially reversible drug-related adverse event. A population-based cohort study demonstrated that cholinesterase inhibitor use was associated with an increased risk of receiving anticholinergic medications to manage urinary incontinence. This study suggests the use of anticholinergic drugs in patients with dementia may sometimes represent an unrecognized ADE related to cholinesterase inhibitor use. The use of anticholinergic drugs by older adults with dementia may expose them to anticholinergic adverse effects (such as urinary retention and postural hypotension) and may also dilute the benefits of cholinesterase inhibitor treatment.
Other prescribing cascade scenarios, such as the association between the use of hydrochlorothiazide therapy and the initiation of antigout therapy or the use of NSAID therapy and hypertension, have been identified. Many more potential prescribing cascades will become apparent as physicians carefully consider the relationship between the initiation of a new drug therapy, the adverse event profile of that therapy, and the development of a new medical condition. The increased recognition of similar prescribing scenarios hopefully will reduce the occurrence of inappropriate prescribing decisions.
Underuse of Beneficial Therapy
Prescribing strategies that seek to simply limit the overall number of drugs prescribed to older adults in the name of improving quality of care may be misdirected. For example, a patient with a myocardial infarction maybe prescribed three essential drug therapies: a beta-blocker, an ACE inhibitor, and acetylsalicylic acid. If this patient has elevated lipid levels and diabetes, three or more additional medications maybe required. Accordingly, many elderly persons may benefit from taking six or more essential medications. Under use of beneficial drug therapy by older adults may be associated with increased morbidity, mortality, and reduced quality of life. This suggests a need for a more complex model for assessing the quality and appropriateness of prescribing for older persons than simply counting the number of different medications that a patient is receiving. This complex model should be directed toward assessing the potential benefit versus harm of the patient’s total medication regimen. One proposed model for the initiation or discontinuation of medications for older adults in late life considers remaining life expectancy, time until benefit will be achieved, the patient’s goals of care and whether the medication can meet treatment goals. For example, if a patient’s life expectancy is short and the goals of care are palliative, then prescribing a prophylactic medication requiring several years to realize a benefit may not be considered appropriate.
For patients of advanced age with multiple medical problems, secondary prevention may not be given a high priority. Among patients 65 years of age or older who have a chronic condition, unrelated diseases often go untreated. Similarly, patients with psychotic syndromes, as indicated by use of haloperidol, were significantly less likely to be dispensed arthritis therapy relative to patients without psychoses (18% relative to 27%, p < 0.001). While an understanding of the logic behind these decisions for individual patients remains uncertain, potential explanations for under treatment include “a belief that treatment of the patient’s primary problem is enough; a judgment that the adverse effects of additional medications are too great and the benefits insufficient; or a patient’s preference for taking fewer medicines.” Selected examples of under prescribing of beneficial therapy are described below.
Despite the availability of guidelines to facilitate hypertension management, this condition is inadequately treated even when physicians are monitoring their patients in a clinic. For example, among 800 men with hypertension with a mean age of 65 years receiving care in Veterans Affairs outpatient clinics in New England, approximately 40% had a blood pressure of 160/90 mm Hg despite an average of more than six hypertension-related visits in a year. At visits in which a diastolic blood pressure of <90 mm Hg and a systolic blood pressure of >165 mm Hg were recorded, increases in the antihypertensive regimen occurred only 22% of the time. The Systolic Hypertension in the Elderly Person (SHEP) study demonstrated that treating isolated systolic hypertension in people 60 years of age and older reduced the risk of stroke by 36% (p = 0.0003) and also reduced major cardiovascular events relative to the placebo condition.
Studies demonstrate that older adults, including those at high-risk for poor outcomes, benefit from beta-blocker therapy postmyocardial infarction. The relation between beta-blocker use and subsequent mortality was evaluated among New Jersey Medicare recipients sustaining an acute myocardial infarction between 1987 and 1992. Among those dispensed beta-blocker therapy, mortality was decreased by 43% relative to nonrecipients of this agent (aRR = 0.57). In a sample of “ideal” beta-blocker therapy candidates in the Cooperative Cardiovascular Project’s cohort of myocardial infarction survivors between 1994 and 1995, being discharged from hospital with a prescription for beta-blocker therapy was associated with a 14% mortality reduction (aRR = 0.86).
Withholding beta-blocker therapy maybe most harmful to seniors of advanced age and with potential contraindications to beta-blocker therapy. Among 201 752 seniors participating in the Cooperative Cardiovascular Project, patients at high-risk for beta-blocker-related complications (i.e., patients with heart failure, pulmonary disease, and diabetes) obtained substantial mortality reduction when prescribed beta-blocker therapy relative to those who were not prescribed this treatment. For example, patients with congestive heart failure treated with beta-blocker therapy had a 40% mortality reduction relative to nonrecipients. While it is impossible to eliminate unmeasured confounding as at least a partial explanation for this survival benefit in recipients versus nonrecipients, observational studies suggest continued under prescribing of beta-blocker therapy to seniors some 20 years after these agents were proven effective in randomized control trials (RCTs).
Osteoporosis is a common condition, particularly among older women. Guidelines are available for the management of the condition (see Chapter 117). To treat osteoporosis, it must first be diagnosed. Despite increasing attention, this condition continues to be underdiagnosed. The findings obtained from the National Osteoporosis Risk Assessment (NORA) study illustrate this problem. The NORA study is a longitudinal observational study of more than 200 000 postmenopausal women to evaluate the relationship between bone mineral density and the risk for fractures. Ambulatory, postmenopausal women with no previous diagnosis of osteoporosis and not on osteoporosis therapy (i.e., bisphosphonate, calcitonin, or raloxifene) were eligible. Of the patients evaluated 39.6% were classified as having osteopenia and 7.2% with osteoporosis. Among the individuals with follow-up information at 1 year, those with osteopenia were almost twice as likely to develop a fracture relative to those with normal bone mineral density. Those older women with a diagnosis of osteoporosis were four times as likely to develop a fracture during the 1 year of follow-up relative to those with a normal bone mineral density. These findings suggest that undiagnosed low bone mineral density is very common in postmenopausal women and is associated with a high rate of fractures. Improved measures aimed at primary prevention in combination with better diagnosis could lead to better outcomes for older women.
Opioid analgesia reduces pain and improves quality of life for cancer patients. Underprescribing of analgesia for cancer pain means that older patients may suffer needless discomfort. Pain guidelines are available to assist physicians in managing pain associated with metastatic cancer. In a study of 1308 outpatients with metastatic cancer being followed by oncologists, 769 patients reported experiencing pain, which 62% described as being substantial. Furthermore, older patients were more likely than younger patients to report that their pain was not being adequately managed. Older persons may be at risk of undertreatment because of a reluctance to prescribe opioid analgesics to older cancer patients. If analgesics are prescribed, the dose may not be adequate to achieve pain control. Efforts to address underprescribing of beneficial therapy in the elderly population must focus on educating health care providers, improving the adherence to prescribed drug regimens by older patients, and reducing the financial barriers to access to essential medications.
Warfarin is recommended in evidence-based guidelines for stroke prevention for older adults with atrial fibrillation, but is often inappropriately prescribed to older adults in long-term care setting. Among 429 residents of long-term care facilities with atrial fibrillation, 42% were prescribed warfarin therapy. Of the 83 older adults who were classified as being “ideal” candidates for warfarin therapy (i.e., no known risk factors for hemorrhage), only half (53%) were prescribed this therapy. Furthermore, international normalized ratio (INR) readings were often found to be either below or above the therapeutic range. In fact, INR values were maintained in the therapeutic range only 51% of the time, placing patients at unnecessary risk for an adverse event despite long-term care residents residing in a supervised setting.
The American Geriatrics Society and the ACOVE project introduced guidelines to address the need for a more systematic approach to decision-making regarding the use of warfarin for stroke prevention in frail older persons. The proposed strategy guides the consideration of appropriate use of warfarin therapy and encourages more frequent monitoring until INR is stable in older adults because of the increased risk of hemorrhage. More widespread use of specialized anticoagulation clinics in order to provide coordinated anticoagulation care may offer an option to improve the effectiveness and safety of warfarin therapy in this particularly high-risk group of patients.
Special Considerations Regarding Drug Therapy in the Long-Term Care Setting
Long-term care residents include a disproportionate number of women, people of advanced age, and those with multiple medical problems, in particular dementia. Of all types of therapeutic interventions, medications are the most commonly used in the nursing home setting. The average U.S. nursing home resident uses six different medications; more than 20% use 10 or more different drugs, placing this group at increased risk of ADEs.
