Polypharmacy and Deprescribing

DefinitionTop

Polypharmacy, the use of multiple medications, is increasingly becoming the norm for older adults. Although there are varying definitions of what constitutes polypharmacy, it is estimated that >60% of older individuals (those aged ≥65 years) use ≥5 prescription medications and ≥20% use >10 medications. Research has revealed that >30% of ambulatory older adults are receiving potentially inappropriate drugs, and the prevalence is even higher in hospital or long-term care settings. This is problematic because the risk of significant harm and adverse drug events rises with increase in the number of agents used. It is estimated that the risk of an adverse drug event is ~10% when using 2 medications but may be as high as 80% when using ≥7 medications.Evidence 1Low Quality of Evidence (low confidence that we know true effects of intervention). Quality of Evidence lowered due to the risk of bias and imprecision. Lavan AH, Gallagher P. Predicting risk of adverse drug reactions in older adults. Ther Adv Drug Saf. 2016 Feb;7(1):11-22. doi: 10.1177/2042098615615472. PMID: 26834959; PMCID: PMC4716390. This chapter introduces a general approach to polypharmacy and outlines strategies that may help with deprescribing and medication optimization.

Polypharmacy is a complex issue that requires careful evaluation and deprescribing (when appropriate) to prevent harm. By addressing polypharmacy, evaluating medication appropriateness, and implementing deprescribing strategies, health-care professionals can enhance patient care, improve health outcomes, and reduce health-care costs.

Deprescribing is the planned and supervised process of tapering or stopping a drug that might no longer be of benefit or even be causing harm. It is a systematic process that considers both the risks associated with a particular drug and collective risk from the concomitant use of multiple drugs. It may involve considerations based on pharmacokinetic and pharmacodynamic interactions, changing medical knowledge, and ongoing (or not) indications for use of individual drugs. The aim is to achieve better patient outcomes and quality of life through the prevention of adverse drug events and geriatric syndromes (eg, falls, cognitive impairment, frailty). Deprescribing can also be initiated based on patient’s goals of care or preference to reduce the pill burden, anticipated life expectancy, relative and absolute potential of benefit, and time needed to benefit.

There is a relative lack of evidence and guidelines to inform deprescribing compared with those that inform the initiation of medications. Studies show that medication review and deprescribing can reliably reduce medication burden, but the impact on patient-important outcomes such as reducing mortality, improving cognition, and mitigating the risk of falls and hospitalization is unclear and inconsistent, depending on the specific setting and patient population. However, current evidence syntheses show that deprescribing can be conducted safely without unintended harms and may even be associated with reduced mortality, especially when patient-specific deprescribing interventions are applied.Evidence 2Low Quality of Evidence (low confidence that we know true effects of intervention). Quality of Evidence lowered due to the risk of bias and imprecision. Page AT, Clifford RM, Potter K, Schwartz D, Etherton-Beer CD. The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016 Sep;82(3):583-623. doi: 10.1111/bcp.12975. Epub 2016 Jun 13. PMID: 27077231; PMCID: PMC5338123. Of note, the medications used in those studies varied, but they included H2 blockers, proton pump inhibitors (PPIs), antiplatelets (acetylsalicylic acid [ASA], clopidogrel), bisphosphonates, glucocorticoids, glucosamine, L-thyroxine, statins, nitrates, diuretics, digoxin, antihypertensives, and anticoagulants.

Deprescribing can also improve medication adherence and pill burden and be cost savingEvidence 3Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to indirectness. Kua CH, Yeo CYY, Tan PC, et al. Association of Deprescribing With Reduction in Mortality and Hospitalization: A Pragmatic Stepped-Wedge Cluster-Randomized Controlled Trial. J Am Med Dir Assoc. 2021;22(1):82-89.e3. doi:10.1016/j.jamda.2020.03.012. PMID: 32423694. to both patients and the health-care system. Medication burden is particularly concerning in aging populations or people with dementia. For example, tid to qid dosing in patients with dementia may induce confusion and cause an elevated risk of overdosing and underdosing of medications, even if blister packs are used. For these reasons deprescribing should be considered part of the prescribing continuum for every medication, especially in older adults with polypharmacy.

Medication Selection, Prescribing, and Deprescribing Top

In order to manage polypharmacy and identify opportunities for deprescribing, it is important to develop knowledge and skill sets related to:

1) Physiologic changes that occur with aging.

2) Prescribing cascades.

3) Drug interactions that increase the risk of harm.

Physiologic, Pharmacokinetic, and Pharmacodynamic Changes in Older Adults

1. Physiologic changes in older adults: Older adults are more vulnerable to adverse drug effects due to physiologic changes that occur with aging as well as pharmacokinetic and pharmacodynamic changes (Table 1). Renal elimination of drugs decreases gradually, leading to the potential accumulation and toxicity of medications. Age-related decreases in gastric motility and changes in body composition can affect drug absorption and distribution. Additionally, hepatic clearance of drugs may be reduced due to decreases in liver mass and blood flow. Therefore, it is crucial for health-care providers to take into account these considerations when selecting and prescribing medications for older adults.

 2. Pharmacokinetic changes in older adults: Decreased renal elimination of drugs is one of the most important changes with aging due to gradually progressive reductions in glomerular filtration. Serum creatinine levels may remain within normal limits because older adults generally have less muscle mass, but this can mislead clinicians to assume that those levels reflect normal kidney function. Without renal dose adjustment, these changes can cause undesired drug accumulation and toxicity in older adults. Estimated glomerular filtration rate (eGFR) should be calculated in these patients every time a renally cleared medication is initiated or its dose is adjusted.

Drug absorption may also be slowed due to age-related decreases in gastric motility and increases in gastric pH. This can result in lower or delayed peak serum concentrations of medications sensitive to these altered environments. Age-related changes in body composition of fat, water, and lean body mass can also alter the usual distribution of hydrophilic and hydrophobic drugs (Table 1). This can lead to clinically significant changes in elimination half-lives and durations of drug action. Since aging decreases liver mass and blood flow, hepatic clearance of drugs (eg, P450 metabolism) may be reduced.

Finally, the blood-brain barrier becomes more permeable with age, which can result in increased sensitivity to the effect of psychotropic and central nervous system (CNS) medications. This makes older adults more susceptible to drug-induced delirium and cognitive impairment.

Digoxin is a medication used for arrhythmias and heart failure. It is well absorbed in the gastrointestinal tract and mainly excreted via the kidneys. Due to its long half-life, patients have a delayed response time, which leads to difficulty in monitoring and making therapeutic adjustments. In older adults the volume of distribution of digoxin is further decreased due to reduced body water and lean body mass, which increases the time it takes to reach the steady-state plasma level concentrations. This should be considered when prescribing loading doses (eg, reduce the dose by ~20%) and when deprescribing. Furthermore, since its elimination is directly proportional to creatinine clearance, the maintenance dose of digoxin should also be reduced based on the renal function in older adults. Prescribers should be cognizant of any dose changes with deprescribing, as the effect of the change (if any) will be reflected later due to the medication's long half-life and time needed to reach a steady state.

 3. Pharmacodynamic changes in older adults: Physiologic changes that occur with aging and generally higher levels of frailty make older adults more susceptible to the effects of medications. Common examples: Table 2.

Prescribing Cascade: Common Mistakes in Practice

A prescribing cascade refers to a sequence of events in which an adverse drug event is misinterpreted as a symptom of a new medical condition and prompts the addition of a new, potentially avoidable medication to treat that symptom. This cascade often leads to inappropriate polypharmacy and further adverse drug events.

One example of a prescribing cascade is when a patient develops a cough after starting an angiotensin-converting enzyme inhibitor (ACEI), later receives a prescription for codeine cough syrup, and then develops constipation and delirium. Selected examples, including the top 9 clinically important prescribing cascades identified by an international multidisciplinary expert consensus panel based on the severity of adverse effects, their frequency of occurrence, and whether the adverse effect can be managed without introducing a second medication: Table 3.

Adverse Drug Interactions that Increase the Risk of Harm

One of the results of polypharmacy and prescribing cascades is multiple drug interactions that can increase the risk of harm for patients. These interactions should be carefully considered when prescribing medications. Selected notable examples: Table 4. Anticholinergic burden can be evaluated using the anticholinergic burden scale (www.acbcalc.com).

ManagementTop

Goals of Deprescribing

Deprescribing interventions should be based on individual risks and patient goals, which can include reducing the risk of geriatric syndromes such as falls and cognitive impairment, mitigating overall medication burden, controlling symptoms and disease progression, or improving clinical health outcomes such as hospitalization and death.

Approach to Deprescribing

Deprescribing is a multistep process that ideally involves:

1) Establishing patient-informed goals for deprescribing: After identifying the goals of care and what matters most to the patient, the first step is to establish clear goals for deprescribing.

2) Collection of the best possible medication history (BPMH): The next crucial step is to gather a comprehensive medication history, encompassing all prescription drugs, over-the-counter medications, vitamins, herbals, and nonoral medications such as topical agents and inhalers. Proper medication reconciliation should include evaluating indications, doses, frequency, and routes for each medication.

3) Assessment of goals of care and time needed to benefit: Based on the indication for use, the value of ongoing treatment should be reassessed in the context of the established goals of care. Consideration should be given to the patient's remaining life expectancy and whether the potential benefit of continued medication outweighs the risk of immediate harm. For example, the appropriateness of statin use in the last year of life should be carefully evaluated. The ePROGNOSIS website can be used to select a validated tool to estimate the life expectancy of a patient.

4) Identification of patient-specific risk factors for adverse drug events: Assessing patient-specific risk factors is crucial in evaluating the potential complications related to polypharmacy. Factors such as advanced age, frailty, number of concurrently used medications, renal and hepatic impairments, and low body mass index (BMI) should be taken into account. Additionally, harmful drug-specific effects and drug-disease interactions, where medication can worsen an existing medical condition or cause a new one, should be considered. Patients with cognitive impairment, dementia, a history of falls, substance abuse, renal impairment, and frailty require closer evaluation.

5) Prioritized deprescribing action plan: Once it is determined that deprescribing should be conducted, medications with the most significant harm or those with negligible benefit should be prioritized for tapering off. During the deprescribing process it is important to monitor for discontinuation syndromes that may occur with certain medications. Medications commonly associated with discontinuation syndrome include alpha-blockers, antimuscarinic agents, ACEIs, benzodiazepines, diuretics, beta-blockers, PPIs, antidepressants, and antipsychotics. Close monitoring of signs and symptoms of discontinuation syndrome is essential. Common examples and signs and symptoms to monitor for each condition: Table 5.

By following this structured approach to deprescribing, health-care professionals can ensure that the process is patient centered, considering individual goals, medication history, risk factors, and an action plan tailored to prioritize the discontinuation of medications with the most potential harm or least benefit.

General Principles of Deprescribing

Prescribers should establish a supportive and trusting relationship with their patients to discuss the complex nature of deprescribing and empower their involvement in this process. In general the dose of each medication can be reduced by 25% of the daily dose every 1 to 4 weeks. If the risk of discontinuation syndrome is high, taper down more slowly; however, if discontinuation is due to profound adverse effects, you can accelerate the tapering schedule. In the presence of recurrent or withdrawal symptoms, revert to the previous dose and continue that dose for 1 to 2 weeks before reattempting to deprescribe. To ensure the identification of any causes of withdrawal symptoms, medication should be deprescribed one at a time.

Some online resources can assist in the deprescribing process (eg, www.deprescribing.org), as they contain deprescribing guidelines and algorithms for many specific drugs. In complex cases and in the presence of significant polypharmacy, it may be beneficial to refer the patient to hospital or a community pharmacist for a more thorough assessment to prevent any adverse outcomes of deprescribing. Lastly, as deprescribing progresses, relevant monitoring parameters such as symptoms, vital signs, electrolytes, and electrocardiograms (ECGs) should be followed.

Deprescribing Challenges in Inpatient Settings

Deprescribing and medication optimization can be challenging to implement during routine encounters due to a variety of factors related to the patient, clinician, and health-care system. Limited time and resources available to engage patients and gather the necessary information to conduct a comprehensive medication review may be a barrier. Other common barriers include lack of accurate medication and related medical information (especially during transitions of care), fear of potential adverse consequences, limited availability of deprescribing guidelines, and patients’ resistance to change.

Despite these challenges, prescribers should not refrain from deprescribing in inpatient settings. Similar challenges exist across all health-care settings and clinicians in primary care are not necessarily better equipped for deprescribing interventions.

Strategies for Deprescribing in Inpatient and Outpatient Settings

As most patients are willing to discontinue their medications if recommended by their physician,Evidence 4Low Quality of Evidence (low confidence that we know true effects of intervention). Quality of Evidence lowered due to the risk of bias and imprecision. Reeve E, Wiese MD, Hendrix I, Roberts MS, Shakib S. People’s attitudes, beliefs, and experiences regarding polypharmacy and willingness to Deprescribe. J Am Geriatr Soc. 2013 Sep;61(9):1508-14. doi: 10.1111/jgs.12418. Epub 2013 Aug 26. PMID: 24028356. prescribers should take more opportunities to review patients’ medications at least weekly or monthly to ensure their continued appropriateness and indication. It is important to weigh the limited evidence for deprescribing with the often limited evidence of benefit of continuing medications (especially in those living with multimorbidity and frailty).

Although more research is needed to increase the feasibility of deprescribing in acute care settings, strategies to facilitate medication optimization may include medication reconciliation standards to ensure timely availability of BPMHs, pharmacist consultation for polypharmacy review, and incorporation of potentially inappropriate medication identification and reassessment into routine checklists for team rounds.

Regular medication reviews can also facilitate good prescribing practices and comprehensive patient care. These reviews should occur at regular intervals (eg, weekly, bimonthly, monthly, or quarterly, depending on the acuity of the patient’s condition and expected length of stay) and could be facilitated by hospital pharmacists to ensure the ongoing necessity, indications, and appropriateness of each prescribed medication.

Recurring deprescribing quality assurance initiatives are another alternative for busy clinical environments with multiple competing priorities. This approach targets specific high-risk medications (eg, 1-2 medications per month) rather than full comprehensive medication reviews to try to improve prescribing appropriateness and gradually reduce problematic polypharmacy. For instance, January could focus on inappropriate benzodiazepine use, February on inappropriate PPI use, and so on.

In the outpatient setting, community pharmacists can be a helpful resource. They may have a greater understanding of the patient’s care journey including prescribers and medication history. The accessibility of a pharmacist allows patients to share additional information, which may provide helpful insights relevant for deprescribing or continuing treatment. Primary care prescribers should communicate and collaborate with community pharmacists to stay up to date with the reasons and needs for chronic medications in patients. By fostering this collaborative relationship, primary care providers can make well-informed decisions regarding medication management and ensure better patient outcomes.

Deprescribing Tools

Several tools are available that have been designed to help with the various stages of deprescribing. Potentially inappropriate medications are defined as those with risks outweighing benefit, those that are misprescribed over another more appropriate option, and those overprescribed despite not needing the therapy.

Two commonly used tools for the identification of potentially inappropriate medications are the Screening Tool of Older People’s Prescriptions (STOPP) and Screening Tool to Alert to the Right Treatment (START) and the Beers Criteria. The STOPP/START includes explicit criteria that facilitate medication review in older people with multimorbidity in most clinical settings. The Beers Criteria contain a consensus list of potentially inappropriate medications for older persons that includes antidepressants, antihypertensives, antiplatelets, anticoagulants, antipsychotics, anti-anxiolytics, CNS agents, and more. Of note, the list is dynamic and changes as the new information is accumulated.

Several deprescribing guidelines and algorithms have been developed to help with deprescribing decision-making, intervention, and monitoring, such as deprescribing.org (DPO), Choosing Wisely Canada (CWC), Best Practice Advocacy Centre New Zealand (BPAC), New South Wales Therapeutic Advisory Group (NSW TAG), Primary Health Tasmania (PHT), as well as other e-learning modules with case-based learning (Table 6). Medications to add in older adults due to their protective effects are not included in this table, although undertreatment is also considered under the potentially inappropriate medication criteria.

TablesTop