The benefits and risks of drug therapy are different for
older people. This primer explains how and why.
Medications are among the most common types of therapy used by older adults. The goals of medication use in older adults are primarily focused on palliating symptoms or maintaining or preventing a decline in functional status. The health status of elders is not static, so there is a need for continual reassessment of drug therapy. This article highlights why the benefit and risk evaluation differs for older versus younger adults. We will also offer practical tips to share with elders about medications, specifically about the use of generic drugs, the proper disposal of medications, and the important questions older individuals should ask their
physician or pharmacist about drugs they take.
Knowledge Base About Medications in Elders
It is often difficult to evaluate the benefits of drug therapy in older adults. One reason is because the elder population is underrepresented in randomized clinical trials, which serve as the basis for drug approval by the United States Food and Drug Administration (Cherubini et al., 2011). Randomized clinical trials are usually designed to compare an active drug with a placebo and are considered the gold standard for determining safety and efficacy of medication use. While differences in treatment versus placebo response can be expressed using statistical (P values) and epidemiological (relative risk) measures, what is most important is how many people need to be treated before a benefit can be seen (Yuan, Levitan, and Berlin, 2011).
In older adults especially it can be difficult to determine the most beneficial treatments with the fewest risks because this patient population is often excluded from clinical drug trials. There are exceptions. For example, the Hypertension in the Very Elderly Trial (HYVET) evaluated the benefits of antihypertensive therapy versus placebo in the very old (eighty years or older) and found that blood pressure lowering was associated with a reduction in mortality in this population (Beckett et al., 2008). And, the placebo-controlled studies that led to the Food and Drug Administration (FDA) approval of memantine (Namenda) for Alzheimer’s Disease enrolled subjects ranging from fifty to ninetythree years of age, with a mean of seventy-six years (Reisberg et al., 2003; Tariot et al., 2004).
In general, however, pre-marketing studies seek homogeneous subjects to help reduce unexplained variations in the outcome measures of interest. Investigating a heterogeneous population (e.g., including older adults with multiple comorbid conditions and medications in the same study as younger, healthier subjects) may muddle the findings of a clinical trial and weaken the probability of detecting response to treatment versus placebo (Strom, 2006).
Practically speaking, older adults are more likely to create an interruption in the trial when they cannot participate (because of acute hospitalization or spousal care needs), making them less desirable as subjects. Some practical barriers can be overcome (providing transportation to and from the study site for subjects with limited mobility or without access to a car); but designing a clinical trial to accommodate participants with varying needs can be costly, time-consuming, and require additional staff.
For these reasons, even when elders are included in clinical trials, the subjects are often relatively healthy and have less comorbidity and a greater ability to tolerate treatment compared to their peers. As a result, the oldest old and frail elders have been grossly underrepresented in clinical trials, causing a lack of evidence for treatment benefits in the population most likely to require therapeutic intervention (Ferrucci et al., 2004). For instance, the benefits of statin medications in reducing the risk of heart attack and stroke have been studied in numerous clinical trials. In adults older than eighty years, however, there is no evidence of benefits from statin therapy, even in those with cardiac disease (Morley, 2011).
Clinical Trial Requirements
Traditionally, clinical trials have studied the following outcomes, usually related to a single disease state: physiologic indicator-biomarker, major clinical event (e.g., heart attack, stroke), and death. Other outcomes relevant to older people include functional status, cognition, mood, quality of life, time at home, and caregiver burden. Although treating a single disease in younger and older adults alike may result in disease-specific improvements, such targeted treatment may have little or no effect on the overall well-being and quality of life of the older patient population.
Geriatric patients may have competing healthcare issues that cannot be addressed by a single drug or treatment approach; therefore, a multifaceted, multi-disciplinary approach to treatment is applied in real-world clinical practice to address the unique physical, mental, emotional, and social issues of older adults. Certainly some young people have complicated medical histories or multiple disease states and take numerous medications, but as a whole, these challenges are more common in and relevant to the geriatric population.
Federal funding agencies require that clinical trials include both genders, represent regional ethnicity, and include children under the age of twenty-one; so investigators must have a scientifically valid rationale to exclude subjects on the basis of gender, ethnicity, or youth. To the contrary, there are no federal regulations mandating clinical trials include older adults (American Geriatrics Society, n.d.). Moreover, comparative effectiveness research (comparing one active drug to another to determine the best drug for certain conditions) is rarely conducted in older adults. Hopefully, forward-thinking programs will help fill this void. One example is the Patient-Centered Outcomes Research Institute, which aims to increase transparency in clinical research and supply patients and providers with evidence-based treatment information.
Questions Older Adults Should Ask Their Physician or Pharmacist
It is important for an older adult to take an active role in decisions made regarding their medication regimens. Not only is it important for older adults to understand what they are taking and how the drug is supposed to work, but also it is equally important for individuals to watch out for problems and get assistance from either their doctor or pharmacist to help solve difficulties. The Center for Medicines and Healthy Aging website (medsandaging.org) offers practical information to assist in the best use of medicine. One specific resource is a list of important questions for older adults to consider asking their doctor or pharmacist. Selected examples of questions include the following:
Medication Guidelines For Older Adults
In the absence of clinical trial evidence in the elder population, clinicians often extrapolate from evidence in younger adults. An assumption is made that clinical practice guidelines developed from research in younger adults can be applied to frail elders. These assumptions may be invalid and even cause harm. A review of the evidence on cholesterol and mortality in persons older than age 80, for example, concluded, “There is not sufficient data to recommend anything regarding initiation or continuation of lipid lowering treatment for the population aged 80+, with known cardiovascular disease (CVD), and it is even possible that statins may increase all-cause mortality in this group of elderly individuals without CVD” (Petersen, Christensen, and Kragstrup, 2010).
In light of this paucity of evidence, expert panels have developed guidelines for medication management in older adults. For example, the Beers Criteria is a list of medications considered to be potentially inappropriate in elders, either because of potential side effects or disease-specific precautions (Beers, 1997; Fick et al., 2003).
Alternatives to the Beers Criteria include the Screening Tool of Older Person’s Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) approaches, which provide explicit guidance regarding inappropriate medications to be stopped and appropriate medications to be started in older adults with specific comorbid conditions (O’Mahony et al., 2010).
Similarly, the Assessing Care Of Vulnerable Elders (ACOVE) quality measurement set is aimed at the comprehensive care of older adults (Shrank, Polinski, and Avorn, 2007). Alternatively, such implicit approaches as the Assessment of Underutilization of Medication and Medication Appropriateness Index can be used on a case-by-case basis to ensure diseases are sufficiently treated and medications are appropriately prescribed (Jeffery et al., 1999; Hanlon et al., 1992).
With these and other approaches to medication evaluation, it is crucial for the clinician to remember that older adults often require multiple medications to treat multiple chronic disease states. It may not be as easy to remove medications from older adults as compared to younger adults because of prescriber and patient reluctance, but the inappropriate prescribing of medications can have worse consequences for elders.
Risks of Medication Use in Elders
Drug-related problems can be classified into three major types: adverse drug reactions (ADR), adverse drug withdrawal reactions (ADWE), and therapeutic failures (TF).
An ADR is traditionally recognized as an adverse event that is likely drug-induced, as determined by a standardized algorithm such as the Naranjo probability scale (Naranjo et al., 1981). This is different than an adverse drug event, which is simply an untoward outcome that occurs during or after clinical use of a drug, whether preventable or not; the drug–event relationship is suspected and plausible but not yet confirmed. ADRs are a leading cause of injury and death in the United States. An estimated 2 million ADRs occur annually, with 350,000 of those occurring in nursing homes alone. In one study, 10.7 percent of hospital admissions in older adults were associated with ADRs (Committee on Identifying and Preventing
Medication Errors, 2007).
While ADRs are the most commonly occurring drug-related problem, two other potential negative outcomes of medication use are worth noting: ADWEs and TFs. An ADWE is defined as a set of signs or symptoms related to the removal of a drug (Gerety et al., 1993). In contrast, a TF is the failure to accomplish the goals of treatment because of inadequate or inappropriate drug therapy (Grymonpre et al., 1988). It is important to note that a TF is not related to the natural progression of disease.
Possible Reasons For Drug-Related Problems
Drug interactions, medication errors, and the use of potentially inappropriate medications commonly contribute to adverse patient outcomes. Patient characteristics or behaviors that may increase the risk of ADRs for older adults include increased age, female sex, medication non-adherence, prior history of an ADR, fragmented medical care, and the presence of multiple diseases or poor health status (Hanlon et al., 2001; O’Neill, 2002; Field et al., 2004).
One of the greatest challenges facing prescribers is the altered response to drugs that can occur in those of advanced age. The reduced functional reserve observed in older adults can put them at greater risk for side effects from drugs because they cannot compensate for or “bounce back” from physiologic stressors as easily as can younger patients.
Additionally, changes to the absorption, distribution, metabolism, and excretion of many drugs result in changes in how drugs affect the patient. For example, various drugs are excreted by the kidneys, and kidney function decreases with age. As such, a drug may be present longer in an older person’s bloodstream, thus increasing that person’s exposure to drug effects—positive, negative, or both.
Another unexpected adverse outcome unique to older adults may not be identified until a drug is made available to the general public. For example, pre-marketing studies of the ophthalmic preparation timolol excluded subjects with pre-existing cardiovascular or respiratory disease. After prescription timolol eyedrops were made available in the United States, however, deaths from drug-related heart block and asthma were reported.
Finally, clinicians often fail to realize that medications can cause or contribute to problems that are common in older adults. They may not consider a medication side effect as a cause of the problem. Often described as geriatric syndromes or geriatric conditions, problems such as falls, cognitive impairment, delirium, and urinary incontinence are frequently the result of medications.
Achieving the Greatest Benefit with the Lowest Risk
Given the number of medication issues older adults and their healthcare providers must consider to optimally utilize drug therapy, several key issues that frequently arise are summarized below.
Generic Versus Brand-Name Drugs
The use of lower-cost generics may allow older adults to afford their medication regimens and increase adherence. However, the topic of the equivalence of generic drugs to their brandname predecessors tends to be controversial. A systematic review and meta-analysis of forty-seven studies comparing generic and brand-name drugs used to treat cardiovascular diseases found no evidence that brand-name drugs were superior (The Medical Letter on Drugs and Therapeutics, 2009).
Continuing claims that generic drugs are inferior to brand-name originals still lack convincing documentation for most drug classes; however, for some narrow therapeutic index drugs (e.g., anticonvulsants and levothyroxine), a prescriber may recommend using one formulation consistently. Because pharmacies frequently switch generic suppliers in order to avoid price fluctuations or supply shortages, use of the brand-name medication for these specific agents may offer the best strategy to ensure use of a consistent formulation.
Proper Disposal of Medications Can Reduce Errors
Proper disposal of expired, unwanted, or unused drugs will help to prevent medication errors and
decrease the chance the older adult or anyone else may accidentally take the medication. For many years, the most common practice for disposal of medications has been flushing down the toilet. But because of environmental concerns about water supply, other methods for disposal are becoming available. Many communities are now offering periodic medicine take-back programs. An individual may contact their city or county trash and recycling service or a local pharmacist to determine if a take-back program is available. If such a program is unavailable, one can dispose of most medicines by mixing the uncrushed tablets or capsules with an unpalatable substance, such as kitty litter or used coffee grounds, placing the mixture in a sealed plastic bag or other container and throwing the container in the household trash.
Table 1 lists disposal instructions for selected medicines that a take-back program will not accept, so flushing these medicines down the sink or toilet is currently the best way to immediately and permanently remove the risk of accidental harm (U.S. Food and Drug Administration, 2010).
Table 1. Medicines Recommended for Disposal by Flushing Down the Sink or Toilet
|Actiq, oral transmucosal lozenge *||Fentanyl citrate|
|Avinza, capsules (extended release)||Morphine sulfate|
|Daytrana, transdermal patch system||Methylphenidate|
|Demerol, tablets *||Meperidine hydrochloride|
|Demerol, oral solution *||Meperidine hydrochloride|
|Diastat/Diastat AcuDial, rectal gel||Diazepam|
|Dilaudid, tablets *||Hydromorphone hydrochloride|
|Dilaudid, oral liquid *||Hydromorphone hydrochloride|
|Dolophine hydrochloride, tablets *||Methadone hydrochloride|
|Duragesic, patch (extended release) *||Fentanyl|
|Embeda, capsules (extended release)||Morphine sulfate; naltrexone hydrochloride|
|Exalgo, tablets (extended release)||Hydromorphone hydrochloride|
|Fentora, tablets (buccal)||Fentanyl citrate|
|Kadian, capsules (extended release)||Morphine sulfate|
|Methadone hydrochloride, oral solution *||Methadone hydrochloride|
|Methadose, tablets *||Methadone hydrochloride|
|Morphine sulfate, tablets (immediate release) *||Morphine sulfate|
|Morphine sulfate, oral solution *||Morphine sulfate|
|MS Contin, tablets (extended release) *||Morphine sulfate|
|Onsolis, soluble film (buccal)||Fentanyl citrate|
|Opana, tablets (immediate release)||Oxymorphone hydrochloride|
|Opana ER, tablets (extended release)||Oxymorphone hydrochloride|
|Oramorph SR, tablets (sustained release)||Morphine sulfate|
|OxyContin, tablets (extended release) *||Oxymorphone hydrochloride|
|Percocet, tablets *||Acetaminophen; oxycodone hydrochloride|
|Percodan, tablets *||Aspirin; oxycodone hydrochloride|
|Xyrem, oral solution||Sodium oxybate|
*These medicines have generic versions available or are only available in generic formulations.
Source: U.S. Food and Drug Administration, 2010.
It is imperative to stress that medications should not be used by any individuals other than for whom they were prescribed; medications should never be shared. There are several medications that could be especially harmful—and potentially fatal—if a single dose were ingested or applied by a child or pet.
Summing Up: Be Wise—Be Informed
The proper use of medications in older adults is particularly challenging. The benefits of the medication may only be assumed or may not be grounded in evidence from use in elderly people. The risks of medications may be greater in this population because of physiological changes from aging, co-morbidities, use of multiple medications, and use of multiple prescribers and pharmacies. It is important for older adults to be informed about medications and to ask questions of their healthcare professionals in order to use their medicines most wisely.
Emily P. Peron, Pharm.D., B.C.P.S., F.A.S.C.P., is a postdoctoral geriatric research fellow in the Department of Medicine (Geriatrics), University of Pittsburgh, Pennsylvania. Christine M. Ruby, Pharm.D., B.C.P.S., F.A.S.C.P., is assistant professor in the Department of Pharmacy and Therapeutics and Department of Medicine (Geriatrics), University of Pittsburgh Schools of Pharmacy and Medicine. She is also a clinical pharmacy specialist in geriatrics at Shadyside Senior Care in Pittsburgh.
Editor’s Note: This article is taken from the Winter 2011-2012 issue of ASA’s quarterly journal, Generations, an issue devoted to the topic “Medications and Aging.” ASA members receive Generations as a membership benefit; non-members may purchase subscriptions or single copies of issues at our online store. Full digital access to current and back issues of Generations is also available to ASA members and Generations subscribers at MetaPress.
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