INAPPROPRIATE MEDICATIONS

Various criteria have been developed by expert panels in Canada [37] and in the United States [38-43] to assess the quality of prescribing practices and medication use in older adult individuals. The most widely used criteria for inappropriate medications are the Beers criteria. (See ‘Beers criteria’ below.)

In another approach, a Drug Burden Index has been modeled incorporating drugs with anticholinergic or sedative effects, total number of medications, and daily dosing [44,45]. An increased drug burden for anticholinergic and sedative medications was associated with impaired performance on mobility and cognitive testing in high-functioning community-based older adults. Zolpidem, in particular, was implicated in 21 percent of emergency department visits for adverse drug events (ADEs) related to psychiatric medication among adults 65 years and older [46].

Total number of medications was not associated with impaired performance when sedatives and anticholinergics were excluded [44,45]. A high Drug Burden Index has been correlated with increased risk for functional decline in community dwellers [45] and with increased risk of falls in residents in long-term care facilities [47].

Anticholinergic activity

Anticholinergic medications are associated with multiple adverse effects to which older individuals are particularly susceptible. Nonetheless, an analysis of United States medication expenditures between 2005 and 2009 found that 23.3 percent of community-dwelling persons >65 years with dementia were prescribed medications with clinically significant anticholinergic activity (AA) [48].

Adverse effects associated with anticholinergic use in older adults include memory impairment, confusion, hallucinations, dry mouth, blurred vision, constipation, nausea, urinary retention, impaired sweating, and tachycardia. A case-control study found an association between anticholinergic use and risk of community-acquired pneumonia [49]. Anticholinergics can precipitate acute glaucoma episode in patients with narrow angle glaucoma and acute urinary retention in patients with benign prostatic hypertrophy. Specific studies of the relationship between dementia and anticholinergic use include the following:

In a population study of 6912 men and women 65 years and older, those taking anticholinergic drugs were at increased risk for cognitive decline and dementia and risk decreased with medication discontinuation [50].

In a population of 3434 men and women age 65 and older in one health care setting, who had no baseline dementia and who were followed for 10 years, the risk of dementia and Alzheimer’s disease increased in a dose-response relationship with use of anticholinergic drug classes (primarily first-generation antihistamines, tricyclic antidepressants, and bladder antimuscarinics) [51].

In another population of 13,004 individuals aged 65 and older, use of anticholinergic medications was also shown to be associated with greater decline in cognition as measured by the Mini-Mental State Examination [52]. In addition, anticholinergic medication use was associated with increased mortality over a two-year period after adjustment for multiple factors, including comorbid health conditions.

At usual doses, AA is most significantly elevated for amitriptylineatropineclozapinedicyclominedoxepin, L-hyoscyamine, thioridazine, and tolterodine [53]. AA also was increased for chlorpromazinediphenhydraminenortriptylineolanzapineoxybutynin, and paroxetine. It is important to recognize that higher doses of an agent with low or moderate AA can produce significant AA effects, and, similarly, the cumulative effects of multiple agents with low AA can produce significant AA effects. A listing of medication classes that contain significant AA is shown in a table.

Alternative drugs with lower AA are available in many classes represented by these drugs. However, adverse drug reactions (ADRs) other than AA should also be taken into account in weighing the clinical benefits of possible substitutions (eg, dyskinesias and sedation with haloperidol and perphenazine).

Multiple scales in addition to the Drug Burden Index have been developed to qualify the AA of medications. In one study, a higher score on each of nine different anticholinergic burden scales was associated with increased risk for hospitalization and length of stay, falls, and medical utilization [54].

Beers criteria

The Beers criteria, initially developed by an expert consensus panel in 1991, are the most widely cited criteria used to assess inappropriate drug prescribing [38]. The criteria are a list of medications considered potentially inappropriate for use in older patients, mostly due to high risk for adverse events. Medications are grouped into five categories: those potentially inappropriate in most older adults, those that should typically be avoided in older adults with certain conditions, drugs to use with caution, drug-drug interactions, and drug dose adjustment based on kidney function. A notable limitation of the criteria is that they are most applicable to clinical care in the United States, as they focus on medications available in that market.

The criteria have been repeatedly updated, most recently in 2019, and are available on the American Geriatrics Society website [55]. Selected changes in the 2019 update are described below:

Avoid the concurrent use of opioids with either benzodiazepines or gabapentinoids, due to the increased risk of overdose and severe sedation-related adverse events such as respiratory depression and death.

Use caution when prescribing trimethoprim-sulfamethoxazole in patients who are taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), and who have decreased creatinine clearance, to avoid hyperkalemia.

H2-receptor antagonists may be used in patients with dementia, although they should be avoided in patients with delirium.

Use caution when recommending aspirin for primary prevention of cardiovascular disease or colorectal cancer in patients age 70 or older (down from previous threshold of 80 years or older), due to increased risk of bleeding.

Avoid the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with a history of falls or fractures.

Avoid the use of sliding-scale insulin regimens (short- or rapid-acting insulin dosed according to current blood glucose levels), due to the risk of hypoglycemia without benefit of improvement in hyperglycemic management, unless patients are also on basal or long-acting insulin.

While the Beers criteria is supported by evidence, the American Geriatrics Society advises that clinicians must consider many factors in prescribing decisions, including using common sense and clinical judgment, understanding that strict adherence to the criteria is not always possible [56].

Several studies using older versions of the Beers criteria have identified that use of drugs identified as “inappropriate” was widespread in the United States, Canada, and Europe [57,58]. For example, in a sample of community-dwelling older adults in the United States, 43 percent used at least one medication that would be deemed potentially inappropriate by the criteria, with nonsteroidal antiinflammatory drugs (NSAIDs) being the most common [59].

Some of the inappropriate drug therapies identified on the Beers list are available as over-the-counter products [60]. This reinforces the need to always consider over-the-counter drug therapies when reviewing a patient’s medications and to educate individuals on potential problems that can arise from the use of over-the-counter preparations.

The Beer’s criteria have been used to monitor quality of care for older adults. Studies of earlier versions of the Beers criteria found that while the criteria did predict some adverse outcomes, results were mixed [61-64].

Other criteria sets

The Screening Tool of Older Person’s Prescriptions (STOPP) criteria, another tool for identifying inappropriate prescribing, was introduced in 2008 and updated in 2015 [65-68]. The 2003 Beers criteria have been compared with the Screening Tool of Older Person’s Prescriptions (STOPP); STOPP and Beers criteria overlapped in several areas, but earlier versions of the Beers criteria used in this comparison contained some drugs no longer in common use, and STOPP includes consideration of drug-drug interactions and duplication of drugs within a class. In two studies, STOPP identified a significantly higher proportion of older people requiring hospitalization as a result of a medication-related adverse event than did the 2003 Beers criteria [65,68]. In a cluster randomized trial in Ireland, presenting attending physicians with potentially inappropriate medications based on the STOPP/START (Screening Tool to Alert doctors to the Right Treatment) criteria reduced the number of adverse drug events and medication costs during the index hospitalization, but did not reduce length of stay [69].

The FORTA (Fit FOR The Aged) list identifies medications rated in four categories (clear benefit; proven but limited efficacy or some safety concerns; questionable efficacy or safety profile, consider alternative; clearly avoid and find alternative) with ratings based on the individual patient’s indication for the medication [70]. The tool, developed in Germany, has undergone consensus validation with a panel of geriatricians [71], but studies of its impact on clinical outcomes are ongoing.

Health care financing administration

The Centers for Medicare and Medicaid Services drug utilization review criteria target eight prescription drug classes (digoxin, calcium channel blockers, ACE inhibitors, H2 receptor antagonists, NSAIDs, benzodiazepines, antipsychotics, and antidepressants) and focus on four types of prescribing problems (inappropriate dose, inappropriate duration of therapy, duplication of therapies, and potential for drug-drug interactions). In one study, 19 percent of 2508 community-dwelling older adults were using one or more medications inappropriately; NSAIDs and benzodiazepines were the drug classes with the most potential problems [42].

Assessing Care of Vulnerable Elders project

Another expert panel has identified quality indicators for appropriate medication use as part of the Assessing Care of Vulnerable Elders (ACOVE) project [72,73]. These indicators begin with practical suggestions on how to improve prescribing practices:

Document the indication for a new drug therapy

Educate patients on the benefits and risks associated with the use of a new therapy

Maintain a current medication list

Document response to therapy

Periodically review the ongoing need for a drug therapy

In addition, these indicators specify drug therapies that either should not be prescribed for older adults or that warrant careful monitoring after they have been initiated.