Polypharmacy and Deprescribing

from: https://www1.racgp.org.au/ajgp/2023/april/deprescribing-considerations-for-older-people-in-g

Background

Medication optimisation is a core component of geriatric medicine and general practice.

As patients age and accumulate chronic diseases, medication regimens become increasingly complex. While many medications remain beneficial, the balance between benefit and harm changes over time due to:

Ageing
Frailty
Multimorbidity
Reduced physiological reserve
Changing goals of care
Limited life expectancy

Deprescribing is therefore a normal part of good prescribing rather than a separate process.

Every medication should be regularly reviewed to determine whether it remains appropriate for the patient today.

Polypharmacy

Definition

There is no universally accepted definition.

Common Australian Definitions

Source	Definition
Australian Commission on Safety and Quality in Health Care	≥5 medications
Quality Indicator Program	≥9 medications

Polypharmacy generally refers to the concurrent use of multiple medications, most commonly defined as five or more medicines.

Prevalence

Approximately 36% of older Australians experience polypharmacy.
Rates are higher in residential aged care facilities.
More than 54% of PBS-dispensed medications are prescribed to Australians aged ≥65 years.

Appropriate vs Inappropriate Polypharmacy

Appropriate Polypharmacy

Occurs when:

Every medication has a current indication.
Benefits outweigh harms.
Therapy is evidence-based.
Treatment aligns with patient goals.

Example:

Heart failure patient receiving:

ACE inhibitor/ARNI
Beta blocker
Mineralocorticoid receptor antagonist
SGLT2 inhibitor
Diuretic

Despite multiple medications, this is appropriate polypharmacy.

Inappropriate Polypharmacy

Occurs when:

No current indication exists.
Harm exceeds benefit.
Duplicate therapy exists.
Prescribing cascades occur.
Medications are continued despite limited expected benefit.

Inappropriate polypharmacy is associated with:

Reduced cognition
Increased mortality
Reduced quality of life
Falls
Drug interactions
Medication errors
Increased healthcare costs

Why Older Adults Are Vulnerable

Older adults are particularly susceptible because of:

Pharmacokinetic Changes

Reduced Renal Function

Results in accumulation of:

Digoxin
Gabapentin
Pregabalin
DOACs

Reduced Hepatic Clearance

Results in prolonged drug effects.

Altered Body Composition

Increased fat mass
Reduced lean body mass
Reduced total body water

Can alter drug distribution.

Pharmacodynamic Changes

Older adults have increased sensitivity to:

Benzodiazepines
Opioids
Antipsychotics
Anticholinergics

Resulting in:

Falls
Delirium
Cognitive impairment

Deprescribing

Deprescribing is:

The planned withdrawal of medications that are causing harm or are no longer providing benefit to the patient.

Deprescribing should be:

Deliberate
Individualised
Evidence-based
Patient-centred

Goals of Deprescribing

Reduce

Pill burden
Anticholinergic burden
Sedative burden
Falls
Delirium
Hospitalisation

Improve

Adherence
Function
Cognition
Quality of life

Align Treatment With

Patient values
Prognosis
Frailty status
Goals of care

Benefits of Deprescribing

Medication Benefits

Fewer medications
Simpler regimens
Better adherence

Clinical Benefits

Potential reduction in:

Falls
Cognitive impairment
Delirium
Adverse drug reactions

Quality of Life Benefits

Reduced treatment burden
Improved independence
Reduced medication-related anxiety

Patient Attitudes Toward Deprescribing

Many clinicians overestimate patient resistance.

Studies demonstrate:

84–90% of patients would be willing to stop one or more medications if their GP recommended it.

Successful deprescribing requires:

Shared decision-making
Clear communication
Patient engagement
Ongoing monitoring

Barriers to Deprescribing

Clinician Barriers

Lack of time
Competing priorities
Uncertainty regarding benefits
Fear of adverse outcomes
Lack of deprescribing experience
Poor communication between healthcare providers

Patient Barriers

Fear of disease recurrence
Dependence on medications
Misunderstanding medication purpose
Resistance to change

System Barriers

Poor care transitions
Inadequate medication reconciliation
Limited access to non-drug therapies
Software limitations
Fragmented care

Potentially Inappropriate Medicines (PIMs)

Medications which where:

Benefit-harm ratio is unfavourable
Evidence is limited
Safer alternatives exist
No clear indication remains

Common Examples

Anticholinergics

Oxybutynin
Amitriptyline
Promethazine
Benztropine

Sedatives

Temazepam
Diazepam
Oxazepam

Antipsychotics

Risperidone
Olanzapine
Quetiapine

Long-term PPIs

Chronic Opioids

PIMs are strongly associated with:

Frailty
Falls
Cognitive impairment
Hospitalisation

Deprescribing Tools and Resources

The following tools are commonly used to identify potentially inappropriate medications (PIMs), assess medication appropriateness, and guide structured deprescribing in older adults.

Tool	Purpose
Beers Criteria	Identifies potentially inappropriate medicines in older adults
STOPP Criteria	Identifies medications that should potentially be stopped
START Criteria	Identifies beneficial medications that may be missing
MATCH-D	Medication review in dementia
CEASE	Structured deprescribing framework
ERASE	Diagnosis-based deprescribing framework
Prescribing and Deprescribing in CKD (Primary Health Tasmania)	Optimising prescribing in chronic kidney disease

CEASE Algorithm

A practical framework for use during a GP consultation.

C – Current Medicines

Review all medications:

Prescription medications
PRN medications
OTC medications
Vitamins
Supplements
Herbal medicines

E – Elevated Risk

Identify medications associated with:

Falls
Delirium
Cognitive impairment
Anticholinergic burden
Sedative burden
Renal impairment

A – Assess

Assess:

Current indication
Expected benefit
Potential harms
Alignment with goals of care

S – Sort

Prioritise medications according to:

Highest risk
Lowest benefit
Patient preference

E – Eliminate

Implement a deprescribing plan:

One medication at a time
Taper where appropriate
Monitor closely

ERASE Approach

Useful when reviewing long medication lists.

E – Evaluate Diagnoses

Review all active diagnoses.

R – Resolved Conditions

Determine whether the original condition still exists.

Examples:

Resolved depression
Healed peptic ulcer
Transient insomnia

A – Ageing Normally

Consider whether symptoms represent normal ageing rather than disease.

Examples:

Mild appetite reduction
Reduced exercise tolerance
Sleep pattern changes

S – Select Targets

Identify medications suitable for withdrawal.

E – Eliminate

Deprescribe using a structured and monitored approach.

STOPP Criteria (Screening Tool of Older Persons’ Prescriptions)

Particularly useful in older adults.

Identifies medications that may be inappropriate due to:

Falls risk
Delirium risk
Drug interactions
Duplication
Disease-specific contraindications

Examples:

Long-term benzodiazepines
Duplicate drug classes
Calcium channel blockers causing severe constipation
NSAIDs in advanced CKD

START Criteria (Screening Tool to Alert to Right Treatment)

The opposite of STOPP.

Identifies beneficial medications that may have been omitted.

Examples:

Anticoagulation in AF
ACE inhibitor in HFrEF
Statin in established ASCVD
Vitamin D in high-risk osteoporosis

Deprescribing should not create under-treatment.

Beers Criteria®

Developed by the American Geriatrics Society.

Provides a list of:

Medications to avoid in older adults
Drug-disease interactions
Drug-drug interactions
Dose adjustment recommendations

Common medications flagged:

Amitriptyline
Oxybutynin
Promethazine
Long-acting benzodiazepines
Sliding-scale insulin

Resource:

AGS Beers Criteria® Overview

MATCH-D Criteria

Medication Appropriateness Tool for Comorbid Health Conditions During Dementia

Australian tool specifically designed for dementia care.

Focuses on:

Goals of care
Dementia severity
Preventive medication burden
Quality of life

Useful when considering:

Statins
Aspirin
Anticoagulants
Antidiabetic medications
Antihypertensives

Stepwise Deprescribing Approach

1. Assess the Patient and Establish Goals of Care

Clarify the patient’s health goals, preferences and priorities.
Consider:
- Frailty
- Cognitive status
- Functional status
- Comorbidities
- Life expectancy
- Risk of falls
- Goals of care, including symptom control, prevention, function or comfort care

2. Obtain a Comprehensive Medication History

Document all:
- Prescription medicines
- PRN medicines
- Over-the-counter medicines
- Vitamins and supplements
- Herbal/traditional medicines
Reconcile the medication list against:
- Patient-held medication list
- Pharmacy dispensing history
- Home Medicines Review (HMR)
- Residential Medication Management Review (RMMR)
- Hospital discharge summaries
- Specialist letters
- My Health Record
Resolve discrepancies with:
- Patient
- Carer/family
- RACF staff
- Community pharmacy

3. Identify Medicines Potentially Suitable for Deprescribing

Consider medicines with:

No current indication
Outdated diagnosis
Duplicate therapy
Minimal expected benefit
High risk of harm
Contraindications
Drug-drug interactions
Drug-disease interactions
Prescribing cascades
Preventive indication but limited life expectancy

4. Assess Ongoing Need for Each Medicine

For each medicine, ask:

Why was it started?
Does the indication still exist?
Is it still effective?
Is it causing harm?
Is the dose appropriate for age, renal function and frailty?
Is monitoring in place?
Would I start this medicine today?

Prioritise review of medicines with:

Highest risk of harm
Lowest expected benefit
High anticholinergic burden
High sedative burden
Falls risk
Cognitive risk

5. Prioritise Medicines for Change

Discuss options with the patient, family or carers.
Prioritise based on:
- Medicine-related harms and benefits
- Patient goals
- Frailty
- Adherence difficulty
- Withdrawal risk
- Likelihood of symptom recurrence
Usually deprescribe:
- One medicine at a time
- Gradually where needed
- Over weeks to months depending on the medicine

6. Implement the Deprescribing Plan

Use a “stop slow, go low” approach.
Taper where clinically appropriate.

Medicines commonly requiring tapering include:

Benzodiazepines
Z-drugs
Opioids
Antidepressants
Antipsychotics
Beta blockers
Corticosteroids
PPIs, often step-down or taper if long-term use

Medicines often stopped without tapering, depending on clinical context:

Vitamins without indication
Duplicate therapies
Many supplements
NSAIDs
Aspirin for primary prevention, if no indication and bleeding risk outweighs benefit

7. Monitor and Follow Up

Monitor for:

Withdrawal symptoms
Return of original symptoms
Adverse drug withdrawal events
Functional change
Cognition
Falls
Pain
Sleep
Mood
Blood pressure
Blood glucose
INR if relevant

Create a written medication management plan and communicate it to:

Patient
Family/carer
Pharmacist
Community pharmacy
RACF staff
Relevant specialists

Medicines Commonly Targeted for Deprescribing

Anticholinergics

Risks:

Delirium
Falls
Cognitive decline
Urinary retention

Examples:

Oxybutynin
Amitriptyline
Promethazine
Benztropine

Benzodiazepines

Risks:

Falls
Dependence
Cognitive impairment
Fractures

Examples:

Diazepam
Temazepam
Oxazepam
Clonazepam

Antipsychotics

Particularly in dementia.

Risks:

Stroke
Sedation
Falls
Increased mortality

Examples:

Risperidone
Quetiapine
Olanzapine

Opioids

Risks:

Sedation
Falls
Constipation
Dependence

Examples:

Oxycodone
Tapentadol
Morphine

PPIs

Long-term risks:

Fractures
Hypomagnesaemia
B12 deficiency
Enteric infections

Review indication regularly.

Antihypertensives

Consider deprescribing if:

Recurrent falls
Orthostatic hypotension
Frailty
Low BP

Hypoglycaemic Agents

Deprescribing guidelines for specific medicines/drug classes
Medicine/drug class	Risk for use in older people	Relevant deprescribing guidelines
Allopurinol	Worsening renal dysfunction and serious skin toxicity	A
Anticholinergics	Cognitive impairment and urinary retention	B
Antihyperglycaemics	Hypoglycaemia and related morbidity	A, C
Antihypertensive agents	Falls	A
Antipsychotics	Parkinsonism or extrapyramidal symptoms, falls	A, B, C
Aspirin	GI bleeding	A
Benzodiazepines and/or Z-drugs	Sedation, falls, confusion, dependence	A, C
Bisphosphonates	Hypocalcaemia	A
Cholinesterase inhibitors and memantine	GI upset, urinary incontinence, bradycardia	A, C
Gabapentinoids	Sedation, ataxia, falls	D
Glaucoma eye drops	Mostly well tolerated but may no longer be indicated if life expectancy is limited	A
NSAIDs	GI bleeding, renal failure, exacerbation of cardiovascular diseases	A
Opioids	Sedation, falls, fractures, dependence	A, B, E
Proton pump inhibitors	Long-term use increases the risk of fractures, altered absorption of nutrients and some medicines	A, B, C, Turner et al³²
Sedating antihistamines	Falls, fractures, confusion, drowsiness	B
SSRIs and SNRIs	Falls	B
Statins	Myopathy, rhabdomyolysis and fatigue	A
Tricyclic antidepressants	Falls, sedation, anticholinergic adverse effects	B
Vitamin D and calcium	Falls, hypercalcaemia	A
A, Primary Health Tasmania (https://www.primaryhealthtas.com.au/resources/deprescribing-resources/); B, New South Wales Therapeutic Advisory Group (http://www.nswtag.org.au/deprescribing-tools/); C, Bruyère Research Institute (https://deprescribing.org/resources/deprescribing-guidelines-algorithms/); D, Canadian Medication Appropriateness and Deprescribing Network (https://www.deprescribingnetwork.ca/patient-handouts); E, Victorian Department of Health (https://www.health.vic.gov.au/sites/default/files/migrated/files/collections/policies-and-guidelines/safe-opiod-use/recommendations-for-deprescribing-or-tapering-opioids—for-health-professionals.pdf). GI, gastrointestinal; NSAIDs, non-steroidal anti-inflammatory drugs; SNRIs, serotonin noradrenaline reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors; Z-drugs, zopiclone, eszopiclone, zaleplon and zolpidem.

Primary Prevention Medications That Can Be Stopped in Elderly Patients

These medications should not be routinely stopped solely because of age. Deprescribing should be individualised based on:

Goals of care
Frailty
Life expectancy
Functional status
Patient preference
Benefit–harm ratio
Primary versus secondary prevention indication

1. Statins for Primary Prevention

Indication

Reduction of ASCVD risk in patients without established cardiovascular disease.

Consider Deprescribing When

Significant frailty
Limited life expectancy
Advanced dementia
Palliative care focus
Intolerable adverse effects:
- Myalgia
- Myopathy
- Fatigue
- Drug interactions
Patient preference to reduce medication burden

Consider Continuing When

Good functional status
Life expectancy >5–10 years
High absolute cardiovascular risk
Well tolerated

Rationale

Benefits of statins for primary prevention generally accrue over years.

In patients with:

Severe frailty
Advanced dementia
Limited life expectancy

the likelihood of experiencing benefit may be low.

2. Antihypertensives for Primary Prevention

Indication

Reduction of cardiovascular risk through blood pressure control.

Consider Deprescribing or Dose Reduction When

Recurrent falls
Orthostatic hypotension
Symptomatic dizziness
Syncope
Frailty
Persistently low BP
Significant polypharmacy

Consider Continuing When

Good functional status
Elevated cardiovascular risk
Well-controlled and tolerated treatment

Rationale

Overtreatment may increase:

Falls
Syncope
Fractures
Hospitalisation

Particularly in frail older adults.

Deprescribing often means:

Reducing doses
Removing one agent

rather than stopping all antihypertensives.

3. Aspirin for Primary Prevention

Indication

Primary prevention of cardiovascular disease.

Consider Deprescribing When

Age >70 years
No established ASCVD
Increased bleeding risk
Previous GI bleeding
Anticoagulant therapy
Frailty

Consider Continuing When

Generally not recommended for primary prevention in most older adults.

Rationale

Current evidence suggests bleeding risk usually exceeds cardiovascular benefit in primary prevention.

This is one of the most common opportunities for deprescribing in older adults.

4. Bisphosphonates

Indication

Prevention of fragility fractures.

Consider Deprescribing (“Drug Holiday”) When

Oral bisphosphonate >5 years
IV bisphosphonate >3 years
Low fracture risk
No recent fractures
Stable BMD

Consider Continuing When

High fracture risk
Previous hip fracture
Multiple vertebral fractures
Very low T-score

Rationale

Benefits persist after cessation because bisphosphonates remain stored in bone.

Long-term therapy increases risk of:

Atypical femoral fractures
Osteonecrosis of the jaw

5. Vitamins and Supplements

Consider Deprescribing When

No evidence-based indication exists.

Examples:

Multivitamins without deficiency
Vitamin C supplements
Routine magnesium supplementation without indication
Fish oil for primary prevention

Usually Continue When Indicated

Vitamin B12 deficiency
Iron deficiency
Osteoporosis-related vitamin D supplementation
Proven nutritional deficiencies

Rationale

Many supplements contribute substantially to pill burden with little proven benefit.

6. Proton Pump Inhibitors (PPIs)

Indication

GORD
Barrett oesophagus
Peptic ulcer disease
NSAID gastroprotection

Consider Deprescribing When

Original indication resolved
NSAID ceased
Short-term dyspepsia treatment completed
No ongoing reflux symptoms

Consider Continuing When

Barrett oesophagus
Severe erosive oesophagitis
Recurrent ulcer disease
Ongoing NSAID/antiplatelet therapy requiring gastroprotection

Rationale

Long-term use may be associated with:

Rebound acid hypersecretion
B12 deficiency
Hypomagnesaemia
Enteric infections

Often best reduced gradually.

7. Antiplatelet Agents for Primary Prevention

Examples

Aspirin
Clopidogrel

Consider Deprescribing When

No history of:
- MI
- Stroke
- TIA
- PAD
- Coronary stent
High bleeding risk
Frailty
Limited life expectancy

Do NOT Deprescribe Routinely When Used for Secondary Prevention

Examples:

Previous MI
Stroke/TIA
Peripheral arterial disease
Coronary stent

These patients often continue to derive substantial benefit.

Rationale

The distinction between primary prevention and secondary prevention is critical.

Stopping antiplatelet therapy in secondary prevention may significantly increase cardiovascular risk.

Potential pitfalls of a deprescribing intervention


Potential consequences	Examples	Suggestions
Return of original disease symptoms	Symptoms of reflux on discontinuation of a proton pump inhibitor Rebound insomnia on discontinuation of temazepam	‘Stop slow, go low’ approach: – short-term pharmacological substitution or management taper the medicine – psychological support (if applicable) – periodic monitoring of the original disease
Adverse drug withdrawal events	Sleep disturbance, tremor, irritability, anxiety, and palpitation on discontinuation of a benzodiazepine	‘Stop slow, go low’ approach: – stop one medicine at a time – taper the medicine close monitoring
Unmasking drug interactions	For patients on warfarin, altered INR on discontinuation of amiodarone	Thorough medication review before deprescribing to identify any potential pharmacokinetic interactions
Damaging patient–doctor relationship	Patients may interpret deprescribing as ‘giving up’	Shared decision making and patient collaboration: – engage patients (and their caregivers) in every step of the intervention – clear explanation of expected risks and benefits – provide written patient information – psychological support where needed
Deprescribing-related complications	An occurrence of myocardial infarction being attributed to discontinuing a statin	Careful consideration of the benefit–harm ratio of a preventative medicine is key, taking into account an individual’s life expectancy – Consider other options for risk management (eg lifestyle changes)Document all reasonable grounds for stopping a medicine
INR, international normalised ratio.

Outcomes and Evidence

Systematic reviews indicate deprescribing does not significantly alter mortality in randomized trials but may reduce mortality in non-randomized settings.
While benefits to overall health outcomes are variable, deprescribing remains feasible and safe, focusing on improving quality of life through patient-centered care.

Case study

The case study of Tom, an 80-year-old man, illustrates a practical application of deprescribing in an older patient with multiple chronic conditions and medications. Here’s a detailed explanation:

Background on Tom’s Condition and Medications

Medical Conditions: Tom has hypercholesterolaemia, hypertension, gout, chronic constipation, and insomnia.
Current Medications:
- Rosuvastatin (10 mg): For hypercholesterolaemia.
- Ramipril (5 mg): For hypertension.
- Hydrochlorothiazide (25 mg): A diuretic for blood pressure management.
- Allopurinol (150 mg): For gout prevention.
- Amitriptyline (10 mg): Likely for insomnia, pain, or mood disorders.
- Docusate sodium/senna (50 mg/8 mg): For chronic constipation.

Identifying the Problem

Patient’s Concerns: Tom mentions side effects, adherence difficulties, and increased treatment burden from his medications. This opens the door to discuss deprescribing.
Patient Engagement: Tom is willing to reduce or stop medications, emphasizing the importance of shared decision-making.

Use of CEASE Algorithm and Deprescribing Tools

Step 1: Medicine Reconciliation: This includes reviewing all of Tom’s medications and considering a Home Medicines Review with a pharmacist.
Step 2: Identifying High-Risk Medications:
- Amitriptyline: Highlighted as potentially inappropriate due to high anticholinergic and sedative properties, which can lead to issues such as orthostatic hypotension, worsening constipation, and may be contributing to a prescribing cascade with docusate/senna.
- Hydrochlorothiazide: Recognized as potentially exacerbating Tom’s gout, creating a possible prescribing cascade with allopurinol.

Benefit-Harm Assessment and Deprescribing Targets

Benefit-Harm Assessment: Factors considered include Tom’s age, overall health, medication burden, and preferences.
Potential Deprescribing Targets:
- Rosuvastatin: Considered for deprescribing if its primary prevention benefits are less significant at Tom’s age.
- Ramipril: May be adjusted based on age-related blood pressure targets.
- Docusate Sodium/Senna: Evidence suggests it may be ineffective.
- Allopurinol: May be considered for discontinuation if gout has been asymptomatic, and diuretics or lifestyle changes have been made.

Prioritization and Deprescribing Strategy

Priority Selection: Amitriptyline was prioritized for cessation due to its higher risk profile and potential harm.
Deprescribing Plan:
- Gradual tapering of amitriptyline, following evidence-based deprescribing guidelines, to minimize withdrawal symptoms.
- Tom was informed about possible effects, expected outcomes, and was given support materials, such as lifestyle modifications for insomnia.

Follow-Up and Next Steps

Monitoring: Tom’s progress would be closely monitored for changes in symptoms or new adverse effects.
Future Deprescribing: If successful with amitriptyline withdrawal, other medications (e.g., docusate, hydrochlorothiazide) could then be considered for deprescribing based on updated assessments.

Key Takeaways

Patient-Centered Approach: Involves engaging with Tom, respecting his preferences, and personalizing care.
Multidisciplinary Collaboration: Pharmacists and nurses may be involved in reviews, patient education, and monitoring.
Safety and Individualization: Tapering high-risk medications and closely monitoring outcomes ensures safety.