Polypharmacy concerns in the geriatric population

Ronna D. Compton, DO, University of Louisville Geriatrics, 400 E. Chestnut St. Suite 170, Louisville, KY 40202.

E-mail address: rdcomp01@louisville.edu.

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“I want quality not quantity.” These words expressed by a geriatric patient, succinctly describe the goal that is important to most geriatric patients and is becoming ever more apparent to family medicine physicians. In focusing on a geriatric patient’s quality of life, it is vital for family medicine physicians to carefully review the patient’s medications and how they may be affecting the patient’s function, cognition, bodily systems, and overall safety. Although there are various guidelines available to assist physicians when prescribing medications to the elderly, many general practitioners feel overwhelmed or uncomfort- able about prescribing to elderly patients with multiple medical conditions.1 As the baby boomers begin to enter the geriatric population and the numbers of geriatric patients receiving primary care continues to increase, it is ever more important that osteopathic family physicians understand the aging process and become more comfortable prescribing to the elderly.

Demographics and challenges

People of the age of 65 years or older presently comprise 12%-13% of the population, and this would be 25% by the year 2040. This population buys 33% of the drugs prescribed and over-the-counter drugs account for 2 out of every 5 medications taken by them. With this population taking multiple medications, more adverse drug events and hospitalizations occur. Adverse drug events account for up to 28% of geriatric hospital admissions and 26 out of every 1000 hospital beds. In the nursing home, $1.33 is spent for adverse drug events for every $1.00 spent on medications.2-4 With the Food and Drug Administration–approval for uses of drugs expanding, more drugs becoming available over the counter, and the formularies for drugs ever changing safely prescribing to the elderly has become increasingly challenging to the osteopathic family physician.

‌Polypharmacy defined

A single definition for polypharmacy does not exist. However, there are 2 predominant definitions recognized in the literature. These are the use of 5 or more medications and the use of more medications (even a single medication) than are clinically warranted.5 According to the second part of this definition, polypharmacy is even the inappropriate use of a single medication. These medications may include prescribed medications, over-the-counter medications, vita- mins, or herbals. In studying the use of medication that is not clinically warranted, 1 study found that 60% of 236 ambulatory elderly patients (age 65 years or older) were taking medications with no indication or that were suboptimal.6 Risk factors for polypharmacy include in- creased age, frequent healthcare visits and multiple providers, white race, and supplemental insurance.5 Poly- pharmacy presents many risks to the patient, including those of inappropriate drug doses, drug-drug interactions, drug- disease interactions, adverse drug events, and nonadherence. Additional consequences of polypharmacy include a higher prevalence of geriatric syndromes, increased morbidity and mortality, and higher medical costs. Studies have also found an association with an increase in hospital admissions and ER visits, functional impairments, malnutrition, dysphagia, an increase risk of falls and fractures, and fatal adverse drug events.⁵ One study of community-dwelling older men demonstrated that the use of 6.5 medications was associated with frailty, 5.5 with disability, 4.5 with falls, and 4.5 with mortality.⁷

‌More medications =  more falls

Polypharmacy is well recognized as a risk factor for fall occurrence in the geriatric population. As the number of medications increases in a geriatric patient’s regimen, the risk of functional decline, frailty, and falls increases. Although patients on multiple medications have multiple medical problems, there has proven to be an increased risk of falls, irrespective of the patient’s medical problems. Kojima et al. have demonstrated in a longitudinal observational study of geriatric outpatients that logistic regression analysis proved that taking 5 or more medications was significantly associated with an increased risk of falls even when an adjustment was made for age, sex, osteoporosis, and the quantity of comorbid conditions.⁸ The exact reason for polypharmacy increasing the risk of falls has not been identified. However, several studies have shown that polypharmacy increases the risk of adverse drug events, interactions between drugs, electrolyte abnormal- ities, problems with balance, and decrease in elimination of the medications from the body.9 All These factors may increase the risk of falls. A study analyzing the association

between polypharmacy and hip fracture found that the risk of hip fracture was 23 times greater for patients aged 85 years or older who were taking 10 or more drugs than for patients who were 65-74 years old and were taking 0-1 medication.9 The risk of hip fracture increases in the elderly as the number of medications being used increases. The increase in risk of falls associated with polypharmacy may also be extrapolated to the younger patients in a family physician’s practice. A population-based case-control study that investigated polypharmacy in 335 people between 25 and 60 years of age who suffered a serious fall and compared them with a control population of 352 individuals found that patients in this age group who took 2 or more prescribed medications were 2.5 times more likely to suffer an injury fall than those taking fewer medications.10 The osteopathic family physician should be aware of the increased risk of falls in any patient with polypharmacy.

Polypharmacy and cognitive changes

Dr Jerry Gurwitz, director of Meyers Primary Care Institute at UMass and a nationally recognized expert on the safe use of medication in the elderly, has previously stated that “when an elderly patient presents with a status change, unless proven otherwise, it should be assumed to be a medication related problem.” Cognition changes in the elderly should be thought to be most likely attributable to medications until another cause is identified. In the hospitalized elderly, delirium commonly causes morbidity and mortality. Medications have been found to be the leading cause of delirium in the elderly in up to 39% of cases.11 Any medication can cause delirium in the elderly, but certain types of medications are more likely to lead to cognitive changes. These include benzodiazepines, anti- cholinergics, antidepressants, and opiods.11 Centrally acting agents increase the risk of delirium. Marcantonio et al. demonstrated that patients taking benzodiazepines are approximately 3 times more likely to develop delirium after surgery.12,13 Some of the commonly used anticholinergics that should be avoided because of the risk of confusion in the elderly include oxybutynin, diphenhydramine, hydrox- yzine, ranitidine, and promethazine. It is also important to inquire about the use of any over-the-counter medications in geriatric patients as most of the sleep aids include diphenhydramine.

Patients with polypharmacy are much more likely to have drug-induced delirium than those without. Along with polypharmacy, several risk factors for delirium in the elderly have been identified in research. These risk factors include 9 or more chronic medications, 12 or more doses of medication per day, 6 or more concurrent chronic dosages, history of a previous adverse drug reaction, low body- weight, age greater than 85 years and an estimated creatinine clearance o50 mL/min.11,14,15 A regular and complete review of medications by the osteopathic family physician is imperative in the care of the geriatric patient. This can prevent drug-related cognitive decline or worsen- ing of an underlying dementia.

‌Physiological changes of aging and polypharmacy: acute renal failure

As we age and drug elimination from the body decreases, drug accumulation and toxicity increases. Most medications exit the body via the kidneys and a decrease in glomerular filtration rate heightens the risk of drug toxicity. This risk indicates that proper prescribing of medications to the elderly requires calculation of the patient’s creatinine clearance (using the Cockcroft-Gault equation) and adjusting medications that require renal dosing appropriately. Exam- ples of medications requiring this dosage adjustment include levofloxacin, enoxaparin, cefepime, metformin, piperacillin- tazobactam, and memantine. These are only a few of the many medications that require renal adjustment and should be prescribed only after calculating creatinine clearance and adjusting the dose appropriately in the elderly. Many studies have found a relationship between polypharmacy and acute renal failure. The mortality rate of patients who were hospitalized for acute renal failure is close to 45%.16 Furthermore, an association between the duration of polypharmacy and the occurrence of acute renal failure has been demonstrated.16 Osteopathic family physicians may prevent acute renal failure in the geriatric patient by avoiding polypharmacy when prescribing, making dosage adjustments based on the patient’s renal function, and not prescribing nephrotoxic medications. Other physiological changes with aging, such as decreased intestinal blood flow, decreased gastric motility, decreased albumin and protein, and reduced metabolic clearance by the liver, are also important considerations when prescribing to the geriatric patient.

‌Prescribing to the geriatric patient: tools for safe prescribing and avoiding polypharmacy

When prescribing to the geriatric patient there are many modifications in prescribing that may be taken by the osteopathic family physician to avoid polypharmacy. Safely prescribing to the geriatric patient with an acute awareness of the adverse effects of polypharmacy can decrease morbidity and mortality. There are several evidence-based tools that are available to the prescriber and can be easily incorporated into daily practice.17 The most commonly recognized tool is the Beers Criteria. This list of medications that are considered inappropriate for use in the elderly is created by experts and published with the support of the American Geriatrics Society. The list has been proven as easy to use with little time requirement for decision making when utilized in daily, busy clinical practice.17 Additionally, these criteria have an easy application that can be integrated into the electronic health record.18 When the prescriber is choosing a medication to prescribe to a geriatric patient, the record may provide real-time feedback about potential inappropri-

ateness of the use of this medication in the elderly and can provide another alternative to prescribe.18 This serves as an efficient mechanism to avoid polypharmacy in the clinical setting. Not all medications that may harm the elderly are included in the Beers Criteria because in some situations there is no safer alternative. Budnitz et al. found that 4 medications or medication classes (warfarin, insulin, oral antiplatelet agents, and oral hypoglycemic agents) were related to adverse drug events in the elderly.18 Although most of these medications are not included in the Beers Criteria, knowledge about possible risks when used in the elderly and understanding the need for close monitoring should allow for safer prescribing by the osteopathic family physician.

In addition to the Beers Criteria, other tools exist to assist physicians with prescribing for the elderly. Two of these include the screening tool to alert doctors to right treatments (START) and the screening tool of older persons’ potentially inappropriate prescriptions (STOPP). An inter- disciplinary team of primary care physicians, geriatricians, pharmacists, geriatric psychiatrists, and pharmacologists created these tools.¹⁷ The START tool has proven to have a high interrater reliability between physicians and pharma- cists.17 The STOPP tool has 65 indicators that are focused mostly on drug-drug and drug-disease interactions. The items are organized by body system and drug class.¹⁷ As a resource, Table 1 lists some of the most common inappropriately used medications in the geriatric patient as assimilated from a review of the Beers Criteria, START, and STOPP tools.

Consistently reviewing a patient’s medications may be the most effective method to decreasing polypharmacy. In 1 study that encouraged Medicare patients to participate in a medication review with their physician, 42% of those participated and 20% reported discontinuation of at least 1 medication after the review. Furthermore, 29% reported a change in dosage and 17% reported that they informed their physician of a new medication. A total of 45% of the physicians in the study reported that they changed their prescribing habits after being involved in the medication reviews.⁵

In conclusion, safe prescribing to the geriatric patient involves an awareness of polypharmacy, recognizing it when it exists, and taking precautions to prevent it. It is important to keep medication regimens as simple as possible with less frequent dosing. Knowing the potential adverse effects of medications and ensuring that there is an indication for each medication being taken by a patient are both important in reducing polypharmacy. Time must be allowed for a thorough review of medications during an office visit and prescriptions must be individualized to the patient with consideration of the pharmacokinetics of the drug, the patient’s medical problems, and the patient’s hepatic and renal function. The patient or caregiver or both must be educated regarding the treatment, and drug-drug and drug-disease interactions must also be considered. The principle that is taught in geriatric medical education of “start low and go slow” is critical in ensuring that the geriatric patient is on the lowest effective dose of the drug and titrations retention, confusion or sedation, dry mouth, constipation, and falls. Increased risk of toxicity with age as clearance decreases. Higher doses increase the risk of toxicity and increased risk of toxicity with higher doses with age because of decreased renal clearance.

treatment and choose rate control when treating atrial fibrillation instead

‌Table 1 Guide to potentially inappropriate medication use in the geriatric patient: some of the most common inappropriately used medications assimilated from the Beers Criteria, START, and STOPP tools18,19

Drug name Bodily system or drug category

Rationale Recommendation

Promethazine Anticholinergic Risk of anticholinergic effects such as urinary Avoid

Hydroxyzine Diphenhydramine Oxybutynin Others

Ranitidine H2 receptor

Risk of CNS effects, confusion, and delirium Avoid

Famotidine Cimetidine Others

antagonists

Alprazolam Benzodiazepines Increased risk of falls, fractures, cognitive Avoid (may be required for seizure disorder,

Diazepam Diazepam Clonazepam Others

impairment, and delirium

end-of-life care, or others). Do not use for insomnia, agitation, or delirium.

Dicyclomine Antispasmodics Anticholinergic effects such as urinary retention, Avoid unless needed for palliative or end-

Scopolamine Others

confusion or sedation, dry mouth, constipation, and falls

of-life care

Nitrofurantoin Antibiotic Risk of pulmonary toxicity, no proven efficacy in

patients with CrCl o60 mL/min

Avoid in patients with CrCl o60 mL/min, do not use as daily UTI suppression therapy

Doxazosin Alpha1 blocker Risk of orthostatic hypotension and falls Avoid use in treating HTN Terazosin

Others

Clonidine Alpha agonist Risk of orthostatic hypotension, bradycardia, and Avoid group, especially do not use

Methyldopa Others

CNS effects

Clonidine as a first-line medication for HTN

Amiodarone Antiarrhythmic Evidence demonstrates less risk with rate control Avoid antiarrhythmics as first-line

Propafenone Sotalol Others

Digoxin Inotropes/ vasopressors

than rhythm control in geriatric patients, toxicity risk with amiodarone.

Avoid at doses higher than 0.125 mg/d

Nifedipine, IR Calcium channel Risk of constipation and hypotension Avoid

Amlodipine Others

blockers

Spironolactone Potassium-sparing

diuretic

Risk of hyperkalemia is increased with age, especially when used with ACEI, ARB, K supplement, etc.

Avoid, especially at doses higher than 25 mg/d and in patients with heart failure or CrCl o30 mL/min

Furosemide Loop diuretic Dehydration, electrolyte imbalance, falls, and Avoid unless using for CHF (safer

Bumetanide

orthostatic hypotension

alternatives as first line for HTN & no evidence of efficacy for dependent ankle edema)

Amitriptyline Tertiary TCAs Risk of sedation, orthostatic hypotension, and Avoid

Imipramine Others

anticholinergic effects (urinary retention, confusion, falls, etc)

Table 1 (continued)

Drug name Bodily system or drug category

Rationale Recommendation

Citalopram SSRIs Risk of hyponatremia may be increased in Use with caution (monitor Na) and avoid in

Fluoxetiine Paroxetine Others

Zolpidem Nonbenzodiazepine

geriatric patients

Risks similar to benzodiazepines (falls, delirium,

patients with significant medical history of hyponatremia

Avoid, especially long term

Eszopiclone Others

hypnotics

etc)

Insulin, sliding scale

Diabetes treatment Increased risk of hypoglycemia Avoid

Glyburide Sulfonylureas Severe hypoglycemia Avoid, especially long acting Glipizide

Others

Megestrol Endocrine/ metabolism

Stimulates appetite well but has little effect on weight and has severe risk of thrombotic events and potentially death in geriatric patients

Avoid

Metoclopramide Prokinetic Risk of EP effects and tardive dyskinesia,

increased in geriatric patients, may exacerbate parkinsonism.

Loperamide Antidiarrheal Risk of delayed diagnosis, risk of toxic

Avoid (use only in gastroparesis and with caution)

Avoid

Diphenoxylate/ atropine

Others

megacolon, may exacerbate infection

Meperidine Opiod Risk of dizziness, orthostatic hypotension, falls,

and neurotoxicity

Ibuprofen NSAIDs Risk of GI bleeding and PUD, risk of

Avoid

Avoid

Diclofenac Aspririn 4325 mg Meloxicam Naproxen Indomethacin Others

nephrotoxicity, may exacerbate HTN

Cyclobenzaprine Muscle relaxants Risk of sedation, fracture, and anticholinergic Avoid

Carisoprodol Metaxolone Methocarbamol Others

effects

CNS ¼ central nervous system; UTI ¼ urinary tract infection; HTN ¼ hypertension; ACEI ¼ angiotensin-converting-enzyme inhibitor; ARB ¼ angiotensin receptor blocker; CHF ¼ congestive heart failure; TCAs ¼ tricyclic antidepressants; SSRIs ¼ serotonin-specific reuptake inhibitors; NSAIDs ¼ nonsteroidal anti-inflammatory drugs; GI ¼ gastrointestinal; PUD ¼ peptic ulcer disease; EP ¼ extrapyramidal.

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