Polypharmacy and Deprescribing

How to Cite This Chapter: Lim K, Papaioannou A, Marr S, Lee J. Polypharmacy and Deprescribing. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.1060.3. Accessed May 30, 2024.
Last Updated: August 26, 2023
Last Reviewed: March 18, 2024
Chapter Information

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

Table 8.2-1. Pharmacokinetic changes in older adults

Physiologic changes with aging

Effects on a drug

Examples of drugs to use with caution (nonexhaustive list)

Clinical implications

Decreased body water

Lower volume of distribution for hydrophilic drugs

Ethanol, lithium

– May result in higher serum levels in older people

 

– Loading and usual maintenance doses (eg, digoxin) need to be reduced in older adults

Decreased lean body mass

Lower volume of distribution of drugs that bind to muscle

Digoxin

Increased fat stores

Higher volume of distribution of lipophilic drugs

Diazepam, fluoxetine, trazodone

Prolonged half-life and duration of action of medications

Decreased plasma protein (eg, albumin) levels

A higher percentage of drugs that is unbound or active

Diazepam, phenytoin, warfarin

Although age-related changes in drug-protein binding are not usually clinically relevant, significant changes in drug effect can occur with rapid changes in albumin related to acute illness or malnutrition

Reduced drug clearance by the liver due to reduction in hepatic volume and blood flow

Drug accumulation can lead to drug toxicity

 

Amlodipine, diazepam, diltiazem, ibuprofen, morphine, naproxen, nortriptyline, trazodone, verapamil

Dose reduction may be required, but adjustments need to be individualized since hepatic drug metabolism varies greatly from person to person

Reduction in first-pass metabolism due to a decrease in liver mass and blood flow

Increased bioavailability of drugs undergoing extensive hepatic first pass

Labetalol, nifedipine, propranolol

Dose reduction may be required

Decreased bioavailability of prodrugs activated in the liver

Enalapril, perindopril

Dose required for the therapeutic effect may be higher than usual

Reduced kidney function leads to decreased renal drug excretion

Drug accumulation and toxicity

Aminoglycoside, digoxin, fluoroquinolones, lithium, water-soluble beta-blockers (eg, atenolol), NSAIDs

Renally excreted drugs need ideal dose adjustment based on calculated creatinine clearancea (or eGFR if not available)

a Use the Cockcroft-Gault method of creatinine clearance calculation to estimate eGFR.

eGFR, estimated glomerular filtration rate; NSAID, nonsteroidal anti-inflammatory drug.

Table 8.2-2. Pharmacodynamic changes in older adults

Medication

Effects on older adults

Benzodiazepines

Due to increased sensitivity to the central nervous system effect of psychotropic drugs such as benzodiazepines, older adults experience an increased risk of sedation, delirium, falls, and fractures

Opioids

Older patients are more sensitive to opioids and generally require lower doses. In addition, they may also experience greater sedation, cognitive impairment, and other adverse effects of the medication. Accumulation of drug metabolites in patients with renal impairment may also have adverse effects requiring dose adjustment or switching to an alternative opioid

Antihypertensives (eg, calcium channel blockers, beta-blockers)

Baroreflex sensitivity declines with age, creating a fall in systolic blood pressure and pulse pressure when standing. If blood pressure is reduced or heart rate is suppressed with medications, compensatory mechanisms may be inadequate and orthostatic and postprandial hypotension problems may occur

Anticholinergic medications (eg, amitriptyline, oxybutynin, dimenhydrinate)

Due to a reduced number of cholinergic neurons in the brain, older adults are more sensitive to medications with anticholinergic effects. This leads to an increased risk of confusion, constipation, urinary retention, blurred vision, orthostatic hypotension, and dry mouth

Table 8.2-3. Prescribing cascade examples

Drug

Common adverse effects

Potential cascade prescriptions

Cardiovascular system

Calcium channel blockers

Peripheral edema

Diuretics

Diuretics

Urinary incontinence

Overactive bladder medications

HMG-CoA reductase inhibitors (statins)

Myalgia, myositis

NSAIDs, opioids

Coagulation system

ASA

Gastric ulcer, GI bleeding

Gastric protective agents

Central nervous system

Antipsychotics

Extrapyramidal symptoms (acute dyskinesias and dystonic reactions)

Antiparkinsonian agents, antipsychotics, benztropine (INN benzatropine)

 Benzodiazepines

Cognitive impairment

Cholinesterase inhibitors or memantine

Paradoxical agitation or agitation secondary to withdrawal

Antipsychotics

SSRIs, SNRIs

Insomnia

Sleep agents (benzodiazepine, benzodiazepine receptor agonists, sedating antidepressants, melatonin)

GI system

PPIs

Iron absorption impairment

Iron supplements

Musculoskeletal system

NSAIDs

Hypertension

Antihypertensive drugs

Urogenital system

Urinary anticholinergics

Cognitive impairment

Cholinesterase inhibitors or memantine

Alpha-1 blockers

Orthostatic hypotension, dizziness

Betahistine, antihistamines, benzodiazepines

ASA, acetylsalicylic acid; GI, gastrointestinal; INN, international nonproprietary name; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor; SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

Table 8.2-4. Drug interactions and their harmful outcomes

Combination

Risk

ACEI + potassium-sparing diuretic

Hyperkalemia

Anticholinergic + anticholinergic

Cognitive decline

CCB + erythromycin or clarithromycin

Hypotension and shock

Concurrent use of ≥3 CNS active drugs

Falls, fracture

Digoxin + nitrofurantoin

Digoxin toxicity

Lithium + loop diuretic or ACEI

Lithium toxicity

Peripheral alpha-1 blocker + loop diuretic

Urinary incontinence in women

Phenytoin + SMX/TMP

Phenytoin toxicity

SU + SMX/TMP, FQ, nitrofurantoin, or cephalexin

Hypoglycemia

Tamoxifen + paroxetine (or other CYP2D6 inhibitors)

Prevention of converting tamoxifen to its active moiety, resulting in increased breast cancer–related deaths

SMX/TMP or trimethoprim alone + ACEI or ARB or spironolactone

Hyperkalemia

Warfarin + SMX/TMP, FQ, fluconazole, amoxicillin, cephalexin, amiodarone

Bleeding

Warfarin + NSAID

GI bleeding

DOAC + SSRI or SNRI

GI bleeding

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CNS, central nervous system; DOAC, direct oral anticoagulant; FQ, fluroquinolone; GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug; SU, sulfonylurea; SMX/TMP, sulfamethoxazole/trimethoprim.

Table 8.2-5. Common examples of drugs associated with discontinuation syndrome

Drug class

Signs and symptoms of discontinuation syndrome

Antidepressants (eg, citalopram, venlafaxine)

Influenza-like symptoms, insomnia, nausea, imbalance, sensory disturbance, hyperarousal

Antipsychotics (eg, quetiapine, risperidone)a

Agitation, insomnia, hallucination, anxiety, depression, tachycardia, nausea, tremor, confusion, hypothermia, sweating

Proton pump inhibitors (eg, omeprazole)

Rebound acid hypersecretion, indigestion, heartburn, regurgitation

Antimuscarinic urinary incontinence agents (eg, oxybutynin)

Blurred vision, diarrhea, irritability, tachycardia, anxiety, depression, psychosis, confusion, nausea

Alpha-blockers (eg, clonidine)

Respiratory tract infection, urinary retention, hypertension

Beta-blockers

Rebound tachycardia, hypertension

Glucocorticoids (eg, prednisone)

Lethargy, general malaise, arthralgia, headaches, mood swings, emotional lability

a Most withdrawal symptoms start within 4 weeks after abrupt antipsychotic discontinuation and may subside after up to 4 weeks. Hyperkinesia may last for months.Evidence 5Low Quality of Evidence (low confidence that we know true effects of intervention). Quality of Evidence lowered due to the risk of bias and inconsistency. Brandt L, Bschor T, Henssler J, et al. Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis. Front Psychiatry. 2020;11:569912. Published 2020 Sep 29. doi:10.3389/fpsyt.2020.569912.

Table 8.2-6. Medications that are potentially inappropriate in persons aged ≥65 years based on STOPP/START and Beers Criteria

Drug class

Considerations

Guideline available

Clinical pearls

Cardiovascular system

Diuretics (loop diuretics, thiazide diuretics)

The indication for a loop diuretic should be reassessed in patients without clinical signs of HF and if used solely for ankle edema

Yes (BPAC, PHT)

Replace furosemide with hydrochlorothiazide for primary hypertension in gout

Antihypertensives

Consider patient’s age, indication for treatment (eg, HF, AF, hypertension, CKD)

Yes (BPAC, PHT)

Use and dose should be reevaluated in normotensive or hypotensive patients and those successful with lifestyle modifications (eg, dietary modification, weight loss, smoking cessation)

Aspirin

ASA dosed >150 mg/d should be reassessed, ASA for primary prevention is not recommended

Yes (PHT)

– Inappropriate prescription of ASA in patients with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event

 – ASA should not be prescribed to treat dizziness not clearly attributable to cerebrovascular disease

Warfarin

– Assess benefits at 6 or 12 months for uncomplicated DVT or PE, respectively

– May not be of benefit unless the patient has chronic AF

Yes (BPAC, PHT)

– Warfarin and NSAIDs should not be used together due to higher risk of gastric ulcer and bleeding

– Continuous use of unnecessary warfarin complicates the lifestyle measures and puts financial burdens

Alpha-blockers

– Harms (headache, dizziness, increased susceptibility to infection, incontinence) outweigh benefits

– Long-term use may also increase the risk of HF

– Reassess the use of alpha-blockers for benign prostatic hyperplasia in men

Yes (PHT)

In older men with >1 episode of incontinence daily another agent should be offered for better control of urinary incontinence

Antihyperlipidemics (eg, statins, fibrates)

Consider patient’s age and time needed to reach therapeutic benefit. Antihyperlipidemics will be part of future cardiovascular event prevention in 5-10 years

Yes (BPAC, DPO, PHT)

Deprescribing may be appropriate in patients with life expectancy <10 years

Central nervous system and psychotropic drugs

Benzodiazepines

Harm outweighs benefit. Benzodiazepines should not be used for insomnia, agitation, and delirium due to high risk of falls

Yes (BPAC, DPO, NSW TAG, PHT)

Benzodiazepines should be reserved for alcohol withdrawal symptoms/delirium tremens or severe generalized anxiety disorder unresponsive to other therapies

Antipsychotics

Harm outweighs benefit. May cause confusion, delirium, and falls

Yes (DPO, NSW TAG, PHT)

Antipsychotics should be reserved for patients with severe BPSD and reassessed with close monitoring

Bisphosphonates

Drug holiday should be considered if used >5 years

Yes (BPAC, PHT)

Unnecessary long-term bisphosphonate use can lead to atypical femoral fracture and jaw osteonecrosis

Anticholinergics (TCA, oxybutynin)

Harms (constipation, dizziness, drowsiness, urinary retention, falls) outweigh benefit

Yes (NSW TAG, PHT)

– Mirabegron may be a better option for overactive bladder disorder in older adults

– Other antidepressants like SSRI or SNRI should be considered over TCA

Fluoxetine (long-acting antidepressant)

Longer half-life can exaggerate the adverse effects of SSRI (agitation, insomnia, anorexia)

Yes (BPAC, NSW TAG)

SSRIs with shorter half-life should be considered (sertraline, escitalopram)

First-generation antihistamines (diphenhydramine, chlorpheniramine)

Harms (drowsiness, dizziness, falls, memory loss, urinary retention) outweigh benefits

Yes (NSW TAG)

Antihistamine use should be limited to 1-2 weeks; for long-term use, a newer generation antihistamine should be considered

Gastrointestinal and musculoskeletal system

NSAIDs

Harms (gastric ulcers, HF worsening, potential drug-drug interactions) outweigh benefits

Yes (BPAC, PHT)

– If employed, NSAIDs should only be used short term

– Use a COX-1 selective agent if possible

– Use gastroprotective agents like PPIs when appropriate

PPIs

Insignificant benefit in patients not requiring gastroprotective measures 

Yes (BPAC, DPO, NSW TAG, PHT)

Ongoing PPI use following cessation of NSAIDs or glucocorticoid therapy should be avoided

Stimulant laxative

May worsen bowel function if used long term unless used concurrently with opiates

No

Consider increasing fiber intake and replace with PEG or lactulose

AF, atrial fibrillation; ASA, acetylsalicylic acid; BPAC, Best Practice Advocacy Centre New Zealand; BPSD, behavioral and psychological symptoms in dementia; COX-1, cyclooxygenase 1; CWC, Choosing Wisely Canada; DPO, deprescribing.org; DVT, deep vein thrombosis; HF, heart failure; NSAID, nonsteroidal anti-inflammatory drug; NSW TAG, New South Wales Therapeutic Advisory Group; PE, pulmonary embolism; PEG, polyethylene glycol; PHT, Primary Health Tasmania; PPI, proton pump inhibitor; SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; START, Screening Tool to Alert to Right Treatment; STOPP, Screening Tool of Older People's Prescriptions; TCA, tricyclic antidepressant.

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