Drug-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, inappropriate treatment, inadequate monitoring, nonadherence, and drug interactions. (See also Overview of Drug Therapy in Older Adults Overview of Drug Therapy in Older Adults Prevalence of prescription drug use increases substantially with age. Survey data from 2010–2011 indicate that almost 90% of older adults regularly take at least 1 prescription drug, almost... read more .)
Drugs may be ineffective in older adults because clinicians under-dose (eg, because of increased concern about adverse effects) or because adherence is poor (eg, because of financial or cognitive limitations).
Adverse drug effects are effects that are unwanted, uncomfortable, or dangerous. Common examples are oversedation, confusion, hallucinations, falls, and bleeding. Among ambulatory people ≥ 65, adverse drug effects occur at a rate of about 50 events per 1000 person-years. Hospitalization rates due to adverse drug effects are 4 times higher in older patients (about 17%) than in younger patients (4%). And 66% of these hospitalizations in older patients are due to 4 drugs or drug classes—warfarin, insulin, oral antiplatelet drugs, and oral hypoglycemic drugs.
Reasons for Drug-Related Problems
Adverse drug effects can occur in any patient, but certain characteristics of older adults make them more susceptible. For example, older adults often take multiple drugs and have age-related changes in pharmacodynamics and pharmacokinetics; both increase the risk of adverse effects.
At any age, adverse drug effects may occur when drugs are prescribed and taken appropriately; eg, new-onset allergic reactions are not predictable or preventable. However, adverse effects are thought to be preventable in at least 25% of cases in older adults. Certain drug classes are commonly involved: antipsychotics, warfarin, antiplatelet agents, hypoglycemic drugs, insulin, antidepressants, and sedative-hypnotics.
In older adults, a number of common causes for adverse drug effects, ineffectiveness, or both are preventable (see table Preventable Causes of Drug-Related Problems Preventable Causes of Drug-Related Problems ). One major cause involves inadequate communication with patients or between health care practitioners (particularly during health care transitions). Many drug-related problems could be prevented if greater attention were given to medication reconciliation when patients are admitted or discharged from the hospital or at other care transitions (transfer from nursing home to hospital, or skilled nursing facility to home) (1-3 References Drug-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, inappropriate treatment, inadequate monitoring, nonadherence... read more ).
A drug given to treat one disease can exacerbate another disease regardless of patient age, but such interactions are of special concern in older adults. Distinguishing often subtle adverse drug effects from the effects of disease is difficult (see table Drug-Disease Interactions of Concern in Older Adults Drug-Disease Interactions of Concern in Older Adults (Based on the American Geriatrics Society 2019 Beers Criteria® Update) ) and may lead to a prescribing cascade.
A prescribing cascade occurs when the adverse effect of a drug is misinterpreted as a symptom or sign of a new disorder and a new drug is prescribed to treat it. The new, unnecessary drug may cause additional adverse effects, which may then be misinterpreted as yet another disorder and treated unnecessarily, and so on.
Many drugs have adverse effects that resemble symptoms of disorders common in older adults or changes due to aging. The following are examples:
Antipsychotics may cause symptoms that resemble Parkinson disease. In older adults, these symptoms may be diagnosed as Parkinson disease and treated with dopaminergic drugs, possibly leading to adverse effects from the antiparkinson drugs (eg, orthostatic hypotension, delirium, hallucinations, nausea).
Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) may be prescribed for patients with dementia. These drugs may cause diarrhea or urinary frequency or urge incontinence. Patients may then be prescribed an anticholinergic drug (eg, oxybutynin) to treat the new symptoms. Thus, an unnecessary drug is added, increasing the risk of adverse drug effects and drug-drug interactions. A better strategy is to reduce the dose of the cholinesterase inhibitor or consider a different treatment for dementia (eg, memantine) with a different mechanism of action.
Calcium channel blockers (eg, amlodipine, nifedipine, felodipine) may be prescribed for patients with hypertension. These drugs may treat the hypertension appropriately, but they may also cause peripheral edema. Patients may then be prescribed diuretic therapy (eg, furosemide), which may then cause hypokalemia necessitating potassium supplementation. A better strategy is to reduce the dose or discontinue the calcium channel blocker in favor of other antihypertensive drugs, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
In older patients, prescribers should always consider the possibility that a new symptom or sign is due to existing drug therapy.
Because older adults often take many drugs, they are particularly vulnerable to drug-drug interactions. Older adults also frequently use medicinal herbs and other dietary supplements Overview of Dietary Supplements Dietary supplements are the most commonly used of all integrative, complementary, and alternative therapies, primarily because they are widely available, relatively inexpensive, and can be bought... read more and may not tell their health care providers. Medicinal herbs can interact with prescribed drugs and lead to adverse effects. For example, ginkgo biloba extract taken with warfarin can increase risk of bleeding, and St. John's wort taken with a selective serotonin reuptake inhibitor (SSRI) can increase risk of serotonin syndrome. Therefore, physicians should ask patients specifically about dietary supplements, including medicinal herbs and vitamin supplements.
Drug-drug interactions in older adults differ little from those in the general population. However, induction of cytochrome P-450 (CYP450) drug metabolism Drug Metabolism The liver is the principal site of drug metabolism (for review, see [ 1]). Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even... read more by certain drugs (eg, phenytoin, carbamazepine, rifampin) may be decreased in older adults; therefore, the change (increase) in drug metabolism may be less pronounced in older adults. Many other drugs inhibit CYP450 metabolism and thus increase the risk of toxicity of drugs that depend on that pathway for elimination. Because older adults typically use a larger number of drugs, they are at greater risk of multiple, difficult-to-predict CYP450 interactions. Also, concurrent use of ≥ 1 drug with similar adverse effects can increase risk or severity of adverse effects.
Monitoring drug use involves
Documenting the indication for a new drug
Keeping a current list of drugs used by the patient in medical records
Monitoring for achievement of therapeutic goals and other responses to new drugs
Monitoring necessary laboratory tests for efficacy or adverse effects
Periodically reviewing drugs for continued need
Such measures are especially important for older patients. Lack of close monitoring, especially after new drugs are prescribed, increases risk of polypharmacy, adverse effects and ineffectiveness. Criteria to facilitate monitoring have been developed by the Health Care Financing Administration expert consensus panel as part of drug utilization review criteria. The criteria focus on inappropriate dosage or duration of therapy, duplication of therapy, and possible drug-drug interactions.
Inappropriate drug selection
A drug is inappropriate if its potential for harm is greater than its potential for benefit. Inappropriate use of a drug may involve
Choice of an unsuitable drug, dose, frequency of dosing, or duration of therapy
Duplication of therapy
Failure to consider drug interactions and appropriate indications for a drug
Appropriate drugs that are mistakenly continued once an acute condition resolves (as may happen when patients move from one health care setting to another and the indication is not reevaluated)
Some classes of drugs are of special concern in older adults Drug Categories of Concern in Older Adults Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for older adults. Some... read more . Some drugs are so problematic that they should be avoided altogether in older adults, some should be avoided only in certain situations, and others can be used but with increased caution. The American Geriatrics Society Beers Criteria® (see table Potentially Inappropriate Drugs in Older Adults Drug-Disease Interactions of Concern in Older Adults (Based on the American Geriatrics Society 2019 Beers Criteria® Update) ) lists potentially inappropriate drugs for older adults by drug class; other similar lists are available (4 References Drug-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, inappropriate treatment, inadequate monitoring, nonadherence... read more ). A list of some drug-therapy alternatives with supporting references is also available (5 References Drug-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, inappropriate treatment, inadequate monitoring, nonadherence... read more ). Clinicians must weigh potential benefits and risks of therapy in each patient. The criteria do not apply to patients at the end-of-life, when drug therapy decisions are much different.
Despite dissemination and knowledge of the American Geriatrics Society Beers Criteria® and other criteria, inappropriate drugs are still being prescribed for older adults; typically, about 20% of community-dwelling older adults receive at least one inappropriate drug. In such patients, risk of adverse effects is increased. In nursing home patients, inappropriate use also increases risk of hospitalization and death. In one study of hospitalized patients, 27.5% received an inappropriate drug.
Some inappropriate drugs (eg, diphenhydramine and oral nonsteroidal anti-inflammatory drugs [NSAIDs]) are available over-the-counter (OTC); thus, clinicians should specifically question patients about use of OTC drugs and discuss with patients the potential problems such drugs can cause.
Older adults are often prescribed drugs (typically, analgesics, proton pump inhibitors, or hypnotics) for minor symptoms (including adverse effects of other drugs) that may be better treated with nonpharmacologic therapies (eg, exercise, physical therapy, massage, dietary changes, cognitive-behavioral therapy) or by lowering the dose of the drug causing adverse effects. Initiating additional drugs is often inappropriate; benefit may be low, costs are increased, and the new drug may lead to additional toxicity.
Solving the problem of inappropriate drug use in older adults requires more than avoiding a short list of drugs and noting drug categories of concern. A patient’s entire drug regimen should also be assessed regularly to determine continued need for a drug, as well as potential benefit versus harm.
Lack of patient adherence
Drug effectiveness is often compromised by lack of patient adherence among the ambulatory older adults. Adherence Adherence to a Drug Regimen Adherence (compliance) is the degree to which a patient follows a treatment regimen. For drugs, adherence requires that the prescription be obtained promptly and the drug be taken as prescribed... read more is affected by many factors, including language barriers, but not by age per se. Up to half of older adults do not take drugs as directed, usually taking less than prescribed (underadherence). Causes are similar to those for younger adults. In addition, the following contribute:
Financial and physical constraints, which may make purchasing drugs difficult
Cognitive problems, which may make taking drugs as instructed difficult
Use of multiple drugs (polypharmacy)
Use of drugs that must be taken several times a day or in a specific manner
Lack of understanding about what a drug is intended to do (benefits) or how to recognize and manage adverse effects (harms)
A regimen using too frequent or too infrequent dosing, multiple drugs, or both may be too complicated for patients to follow. Clinicians should assess patients’ health literacy and abilities to adhere to a drug regimen (eg, dexterity, hand strength, cognition, vision) and try to accommodate their limitations—eg, by arranging for or recommending easy-access containers, drug labels and instructions in large type, containers equipped with reminder alarms, containers filled based on daily drug needs, reminder telephone calls, or medication assistance. Pharmacists and nurses can help by providing education and reviewing prescription instructions with older adults at each encounter. Pharmacists may be able to identify a problem by noting whether patients obtain refills on schedule or whether a prescription seems illogical or incorrect. Many pharmacies can monitor refill patterns and contact patients and/or prescribers if prescriptions are not being refilled at appropriate intervals.
An excessive dose of an appropriate drug may be prescribed for older adults if the prescriber does not consider age-related changes that affect pharmacokinetics Pharmacokinetics in Older Adults Pharmacokinetics is best defined as what the body does to the drug; it includes Absorption Distribution across body compartments Metabolism Excretion read more and pharmacodynamics Pharmacodynamics in Older Adults In contrast to pharmacokinetic effects, pharmacodynamics is defined as what the drug does to the body or the response of the body to the drug; it is affected by receptor binding, postreceptor... read more . For example, doses of renally cleared drugs (eg, gabapentin, some antimicrobials, digoxin) should be adjusted in patients with renal impairment.
Generally, although dose requirements vary considerably from person to person, drugs should be started at the lowest dose in older adults. Typically, starting doses of about one third to one half the usual adult dose are indicated when a drug has a narrow therapeutic index, when another condition may be exacerbated by a drug, and particularly when patients are frail. The dose is then titrated upward as tolerated to the desired effect. When the dose is increased, patients should be evaluated for adverse effects, and drug levels should be monitored when possible.
Overdosage can also occur when drug interactions Drug-drug interactions Drug-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, inappropriate treatment, inadequate monitoring, nonadherence... read more increase the amount of drug available or when different practitioners prescribe a drug and are unaware that another practitioner prescribed the same or a similar drug (therapeutic duplication).
Poor communication of medical information at transition points (from one health care setting to another) causes up to 50% of all drug errors and up to 20% of adverse drug effects in the hospital. When patients are discharged from the hospital, drug regimens that were started and needed only in the hospital (eg, sedative hypnotics, laxatives, proton pump inhibitors) may be unnecessarily continued by the discharging prescriber. This can be due to carelessness or lack of time or ability to communicate with the primary care prescriber. Conversely, at admission to a health care facility, lack of communication may result in unintentional omission of a necessary maintenance drug. Drug reconciliation refers to a formal process of reviewing all prescribed drugs at each transition of care and can help eliminate errors and omissions.
Appropriate drugs may be underprescribed—ie, not used for maximum effectiveness. Underprescribing may increase morbidity and mortality and reduce quality of life. Clinicians should use adequate drug doses and, when indicated, multidrug regimens.
Drugs that are often underprescribed in older adults include those used to treat depression, Alzheimer disease, heart failure, post-myocardial infarction (beta-blockers), atrial fibrillation (anticoagulants), and hypertension. Also, immunizations are not always given as recommended.
Beta-blockers: In patients with a history of myocardial infarction and/or heart failure, even in older patients at high risk of complications (eg, those with pulmonary disorders or diabetes), these drugs reduce mortality rates and hospitalizations.
Antihypertensives: Guidelines for treating hypertension in older adults are available, and treatment appears to be beneficial (reducing risk of stroke and major cardiovascular events) even in frail older adults. Nonetheless, studies indicate that hypertension is often not optimally controlled in older patients.
Drugs for Alzheimer disease: Acetylcholinesterase inhibitors and NMDA (N-methyl-d-aspartate) antagonists have been shown to benefit patients with Alzheimer disease. The amount of benefit is modest and variable, but patients and family members should be given the opportunity to make an informed decision about their use.
Anticoagulants: Anticoagulants (both warfarin and the newer direct oral anticoagulant drugs) reduce risk of stroke in patients with atrial fibrillation. Although there is an increased risk of bleeding with anticoagulation in general, some older adults who might benefit from anticoagulation are not receiving it.
Immunizations: Older adults are at greater risk of morbidity and mortality resulting from influenza, pneumococcal infection, and herpes zoster. Vaccination rates among older adults can still be improved.
In older patients with a chronic disorder, acute or unrelated disorders may be undertreated (eg, hypercholesterolemia may be untreated in patients with COPD [chronic obstructive pulmonary disease]). Clinicians may withhold these treatments because they are concerned about increasing the risk of adverse effects or the time required to benefit from treatment in a patient with reduced life expectancy. Clinicians may think that treatment of the primary problem is all patients can or want to handle or that patients cannot afford the additional drugs. Patients and caregivers should be active participants in decision making about drug treatment so that clinicians can understand patients' priorities and concerns.
1. Tam VC, Knowles SR, Cornish PL, et al: Frequency, type and clinical importance of medication history errors at admission to hospital: a systematic review. CMAJ 173(5):510-5, 2005. doi: 10.1503/cmaj.045311
2. Wong JD, Bajcar JM, Wong GG, et al: Medication reconciliation at hospital discharge: evaluating discrepancies. Ann Pharmacother 42(10):1373-9, 2008. doi: 10.1345/aph.1L190
3. Forster AJ, Clark HD, Menard A, et al: Adverse events among medical patients after discharge from hospital. CMAJ 170(3):345-9.
4. The American Geriatrics Society 2019 Beers Criteria Update Expert Panel: American Geriatrics Society updated Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc 67(4):674-694, 2019. doi:10.1111/jgs.15767
5. Hanlon JT, Semla TP, Schmader KE, et al: Alternative medications for medications in the use of high-risk medications in the elderly and potentially harmful drug-disease interactions in the elderly quality measures. J Am Geriatr Soc 63(12): e8-e18, 2015. doi: 10.1111/jgs.13807
Before starting a new drug
To reduce the risk of adverse drug effects in older adults, clinicians should do the following before starting a new drug:
Consider nondrug treatment
Discuss goals of care with the patient and/or caregivers and establish a timeframe in which benefit from the drug therapy is expected
Evaluate the indication for each new drug (to avoid using unnecessary drugs)
Consider age-related changes in pharmacokinetics or pharmacodynamics and their effect on dosing requirements
Choose the safest possible drug treatment for the indication (eg, for noninflammatory arthritis, acetaminophen instead of an oral nonsteroidal anti-inflammatory drug [NSAID])
Check for potential drug-disease and drug-drug interactions
Start with the lowest effective dose
Use the fewest drugs necessary
Note coexisting disorders and their likelihood of contributing to adverse drug effects
Explain the uses and adverse effects of each drug
Provide clear instructions to patients about how to take their drugs (including generic and brand names, spelling of each drug name, indication for each drug, and explanation of formulations that contain more than one drug) and for how long the drug will likely be necessary
Anticipate confusion due to sound-alike drug names and pointing out any names that could be confused (eg, Glucophage® and Glucovance®)
After starting a drug
The following should be done after starting a drug:
Monitor patients for signs of adverse drug effects, including measuring drug levels and doing other laboratory tests as necessary.
Document the response to therapy and increase doses as necessary to achieve the desired effect.
Regularly reevaluate the need to continue drug therapy and stop drugs that are no longer necessary or drugs with greater potential risk than benefit.
The following should be ongoing:
Medication reconciliation is a process that helps ensure transfer of information about drug regimens at any transition point in the health care system. The process includes identifying and listing all drugs patients are taking (name, dose, frequency, route) and comparing the resulting list with the physician’s orders at a transition point. Medication reconciliation should occur at each move (admission, transfer, and discharge).
Computerized physician ordering programs can alert clinicians to potential problems (eg, allergy, need for reduced dosage in patients with impaired renal function, drug-drug interactions). These programs can also cue clinicians to monitor certain patients closely for adverse drug effects.