From Healing to Harm: The Unintended Consequences of Polypharmacy in Seniors

By Cynthia Nwaubani, PharmD, BCGP

Polypharmacy, or the concurrent use of at least five medications, can be essential for individuals with multiple chronic conditions. When medications are prescribed with clear therapeutic objectives, optimized to minimize adverse drug reactions (ADRs), and the patient adheres to the regimen, polypharmacy can be appropriate and beneficial. However, it often becomes excessive and hazardous when medications are unnecessary, fail to meet therapeutic goals, pose a high risk of ADRs, or when the patient is non-compliant.

While medications have greatly improved health outcomes worldwide, the use of multiple drugs significantly increases the risk of serious life-threatening side effects. In recent decades, medication use in the U.S., particularly among older adults, has surged beyond what is necessary. This has resulted in millions of individuals being overburdened with excessive prescriptions, leading to significant harm and skyrocketing costs.

Every day, 750 seniors (age 65 and older) in the United States are hospitalized due to serious side effects from one or more medications.(Shehab et al. JAMA 2016; 316(20): 2115-25.)

Risks of Polypharmacy

Polypharmacy is associated with several categories of adverse effects, each with significant implications for patient health, safety and total cost of care. These include: 

1. Drug-Drug Interactions 

Polypharmacy significantly increases the risk of drug-drug interactions, particularly in older adults. According to a study published in the Journal of the American Medical Association (JAMA), nearly 50% of older adults take at least one medication that has the potential to interact with another drug they are taking.

Pharmacodynamic Interactions occur when multiple medications affect the same physiological processes, leading to amplified or diminished drug effects. For instance, combining CNS depressants can cause excessive sedation.

Pharmacokinetic Interactions involve changes in the absorption, distribution, metabolism, or excretion of one drug caused by another. For example, certain medications can inhibit liver enzymes responsible for drug metabolism, leading to increased blood levels of other drugs and potential toxicity. These interactions can result in unpredictable therapeutic outcomes, serious health complications, and increased mortality rates. 

People over 65 make up only 14% of the population but account for 56% of hospitalizations for adverse drug events (ADEs) (Agency for Healthcare Research and Quality, AHRQ, 2021). Additionally, less than half of those experiencing an ADE recognize it and seek medical treatment, meaning about ten million older adults in the U.S.—roughly one in five—suffer from an ADE each year (National Institute on Aging, NIH, 2021).

2. Adverse Drug Reactions (ADRs)

Adverse drug reactions are a major concern in polypharmacy. Each additional medication increases the risk due to the cumulative effect of multiple drugs. The side effects can compound, resulting in a greater negative impact on a patient’s health than the individual effects of one medication alone. Common side effects include dizziness, confusion, and sedation, significantly impairing an older adult’s ability to function independently. According to the American Geriatrics Society, adverse drug reactions account for approximately 10% of emergency department visits and 25% of hospital admissions among older adults.

3. Cognitive Impairment

Polypharmacy is closely linked to significant cognitive and psychological adverse effects, especially in older adults. Medications with anticholinergic properties, sedatives, or those affecting neurotransmitter function can impair cognitive function, leading to confusion, memory loss, and reduced attention span. Prolonged use of these medications is associated with an increased risk of developing dementia.

An illustrative case is Mrs. Lewis, a 78-year-old woman who began experiencing confusion and memory lapses after her physician prescribed a new medication for her overactive bladder. Initially misdiagnosed with early-stage dementia, it was later discovered that her symptoms were due to the cumulative anticholinergic burden from her medications. Studies have shown that high cumulative anticholinergic exposure significantly increases the risk of dementia (Campbell et al., 2012).

4. Increased Risk of Falls and Physical Injuries

Polypharmacy poses significant challenges in geriatric care due to the increased risk of adverse physical effects. Medications like selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, sedatives, hypnotics, and antihypertensives, although beneficial individually, collectively heighten the risk of falls and fractures in the elderly. This risk is not just theoretical but leads to real-world consequences that significantly affect the quality of life and independence of older adults.

A case in point is Mr. Patel, an 80-year-old managing hypertension, chronic pain, and insomnia. He frequently experienced dizziness, a side effect exacerbated by his complex medication regimen. Unfortunately, this led to a severe fall one night while heading to the bathroom, resulting in a serious head injury.

5. Medication Non-Adherence

Polypharmacy increases the likelihood of medication non-adherence due to the complexity and confusion of managing multiple medications.Patients often struggle with the regimen, missing doses, taking incorrect dosages, or discontinuing medications altogether, which can lead to suboptimal treatment results. Moreover, the financial burden of covering the cost for numerous medications can overwhelm patients, further hindering adherence. Together, these challenges not only aggravate existing health conditions but also increase the likelihood of expensive hospitalizations and readmissions.

6: Prescribing Cascade 

The prescribing cascade occurs when the side effects of a medication are misinterpreted as a new medical condition, leading to the prescription of additional medications to treat these side effects. This phenomenon can quickly escalate, especially in older adults, who are more susceptible to medication side effects due to age-related changes in pharmacokinetics and pharmacodynamics. (American Geriatrics Society, 2021)

For example, a patient prescribed a calcium channel blocker for hypertension may develop peripheral edema, a known side effect. Instead of recognizing the calcium channel blocker as the cause, a physician might prescribe a diuretic to treat the edema, initiating a prescribing cascade.A study in the Archives of Internal Medicine found that nearly 20% of older adults on new medications experienced a prescribing cascade (Archives of Internal Medicine, 2012).

Impact of Polypharmacy

1. Quality of Life

Physical Health: The cumulative side effects and interactions from multiple medications can significantly deteriorate physical health. Older adults, in particular, are vulnerable to adverse drug reactions (ADRs) due to age-related changes in drug metabolism and excretion. Chronic conditions may also be exacerbated by inappropriate medication use, leading to a decline in overall health and functionality. 

Mental Health: Managing multiple medications can be stressful and confusing, leading to anxiety, depression, and cognitive impairment. The burden of adhering to complex medication regimens can result in a decreased sense of well-being and mental fatigue. The psychological strain of managing chronic illnesses alongside polypharmacy can diminish a patient’s quality of life, making everyday tasks more challenging and increasing the risk of mental health disorders (Jyrkka et al., 2011).

2. Healthcare System 

Resource Utilization: Polypharmacy management requires significant healthcare resources, including frequent medical consultations, regular blood tests, and continuous monitoring of drug efficacy and interactions. Healthcare providers review medication lists, adjust dosages, and coordinate care among multiple specialists. This intensive resource utilization can strain healthcare systems, especially those already under pressure from high patient volumes and limited staffing (Maher et al., 2014).

Higher Costs: Polypharmacy’s economic impact is substantial. Increased hospitalizations and emergency visits due to ADRs and drug interactions contribute significantly to healthcare costs. The direct costs of purchasing multiple medications financially strain patients and healthcare systems. Additionally, indirect costs such as lost productivity, extended recovery times, and long-term care needs exacerbate the financial burden. It is estimated that polypharmacy contributes to an additional $3 billion annually in healthcare costs in the U.S. (Watanabe et al., 2018).

3. Patient Safety

Medication Errors: The risk of medication errors rises with the number of medications a patient takes. Errors can occur in prescribing, dispensing, or administering medications. These errors can lead to serious health complications, including overdose, underdose, and harmful drug interactions. Ensuring accurate medication management is critical to patient safety but becomes increasingly complex with polypharmacy. The Institute of Medicine estimates that medication errors harm at least 1.5 million people annually in the U.S. (Institute of Medicine, 2006).

4. Social Impact

Caregiver Burden: Managing complex medication regimens can be time-consuming and stressful for family members and caregivers, often leading to burnout. Ensuring medications are taken correctly requires constant vigilance and coordination, which is especially burdensome with polypharmacy. This responsibility impacts caregivers’ health and well-being, with approximately 20% reporting high physical strain and 40% experiencing emotional stress (Family Caregiver Alliance, 2016).

Loss of Independence: Older adults may lose their independence as they become increasingly reliant on others for medication management and daily activities. This dependency can affect their self-esteem and quality of life. As medication regimens become more complex, older adults may struggle to maintain their autonomy, leading to a greater need for assisted living or long-term care facilities. This loss of independence can be particularly distressing for individuals who value their ability to live independently (Gnjidic et al., 2012).

Conclusion:

As we conclude Part 2 of our series on polypharmacy, clinical studies and real-world patient cases reveal its significant complexities and dangers. These scenarios vividly illustrate how polypharmacy can lead to a cascade of negative health outcomes, underscoring the critical need for healthcare professionals to meticulously balance the benefits and risks of each prescribed medication. Detailed medication histories and careful consideration of whether new symptoms are side effects of existing drugs are essential, especially when managing complex regimens in elderly patients. Stay tuned for Part 3, where we will discuss identifying and addressing polypharmacy.

References:

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