What strategies should be used to manage polypharmacy in patients aged 65 and older to minimize fall risk?

Managing Polypharmacy to Reduce Fall Risk in Older Adults

Implement systematic deprescribing using a 9-step medication review process, prioritizing elimination of high-risk fall medications including benzodiazepines, sedative-hypnotics, anticholinergics, antipsychotics, and opioids in patients aged 65 and older taking 5 or more medications. 1

Understanding the Risk

Polypharmacy (typically defined as ≥5 medications) directly increases fall risk in older adults, with hospitalization rates from falls escalating from 1.5% in those taking no medications to 14.8% in those taking 10+ medications. 2 The risk of fall-related hospitalization increases 1.75-fold with polypharmacy (5-9 medications) and 3.19-fold with heightened polypharmacy (≥10 medications) compared to those taking no medications. 2

Falls are the leading cause of injury-related morbidity and mortality in older adults, affecting 28.7% of community-dwelling adults ≥65 years annually, resulting in approximately 33,000 deaths. 3

The 9-Step Systematic Medication Review Process

The Mayo Clinic Proceedings guideline provides a structured approach to identify and eliminate drug therapy problems: 1

Step 1: Medication Reconciliation

• Document what the patient actually takes (not just what's prescribed), including discontinued medications, unfilled prescriptions, and incorrect dosing. 1
• Stop, modify, or initiate appropriate therapy based on discrepancies. 1

Step 2: Adherence Assessment

• Identify barriers such as complex dosing schedules (3-4 times daily), cost issues, missing inhalers, or side effects. 1
• Simplify regimens to reduce daily dosing frequency and eliminate agents causing adverse effects. 1

Step 3: Drug-Drug Interaction Screening

• Screen for high-risk interactions including QT prolongation, anticoagulant combinations increasing bleeding risk, NSAIDs with anticoagulants, and serotonin syndrome risk. 1
• Select non-interacting alternatives when risk outweighs benefit. 1

Step 4: Drug-Disease Interaction Review

• Identify contraindicated combinations such as NSAIDs in heart failure, chronic kidney disease, or hypertension; sulfonylureas in kidney disease. 1
• Choose alternative therapies that don't exacerbate underlying conditions. 1

Step 5: Eliminate Duplicate Therapy

• Remove redundant medications and those with additive side effects causing toxicity. 1
• Adjust doses and taper therapy appropriately. 1

Step 6: Apply Beers Criteria and STOPP/START Tools

This is the critical step for fall prevention. Target these high-risk medication classes: 1

• Sedative-hypnotics
• Opioids
• Anticholinergics (diphenhydramine, cyclobenzaprine, oxybutynin)
• Benzodiazepines
• Anxiolytics
• Hypoglycemic agents (sulfonylureas, short-acting insulin)

Educate patients about avoiding over-the-counter anticholinergic medications. 1

Step 7: Identify Undertreated Conditions

• Ensure indicated medications aren't overlooked in complex regimens (e.g., statins in coronary artery disease, antiplatelet agents after stenting). 1
• Balance deprescribing with maintaining beneficial therapies. 1

Step 8: Monitor for Efficacy and Safety

• Establish appropriate monitoring including routine labs (TSH, INR for warfarin), drug levels, and kidney/liver function assessments. 1

Step 9: Evaluate Supplements

• Discontinue non-contributive supplements (multivitamins, iron, trace elements) that add to medication burden, cost, and interaction risk. 1
• Exception: Continue recommended supplements like vitamin D. 1

Priority Medications to Deprescribe for Fall Prevention

Anticholinergic Medications

Strongly anticholinergic drugs are poorly tolerated and cause vision impairment, urinary retention, constipation, and cognitive decline—all increasing fall risk. 1 Target older antihistamines (diphenhydramine), muscle relaxants (cyclobenzaprine), and overactive bladder agents (oxybutynin) for elimination. 1

Hypoglycemic Agents

Episodic hypoglycemia is a leading cause of emergency department admissions in older patients. 1 Deintensify diabetes regimens, particularly sulfonylureas and short-acting insulin, and relax hemoglobin A1c goals. 1

Antipsychotics

Recent evidence shows discontinuing antipsychotics in patients with a previous fall reduces subsequent fall risk (HR 0.32). 4 This represents the strongest evidence for a specific medication class reduction preventing falls. 4

Benzodiazepines and Opioids

These require patient and family education about risks, with gradual tapering protocols. 1 Best practices include obtaining agreement from patients, families, and care teams before initiating deprescribing. 1

Important Caveats

General FRID (fall-risk-increasing drug) discontinuation does not universally reduce falls. A 2025 study of 1,546 multimorbid older adults found no overall association between FRID discontinuation and fall reduction, except for antipsychotics in those with prior falls. 4 This highlights that deprescribing must be targeted and strategic, not blanket removal of all potentially risky medications. 4

Taking ≥4 medications is associated with increased incidence of falls, recurrent falls, and injurious falls. 5 However, the number alone shouldn't drive decisions—focus on the specific high-risk classes identified above. 5

Complementary Fall Prevention Strategies

While managing polypharmacy, implement exercise interventions for patients at increased risk for falls (USPSTF Grade B recommendation). 3 Exercise has moderate benefit in preventing falls with adequate supporting evidence. 3

Do not recommend vitamin D supplementation solely for fall prevention (USPSTF Grade D recommendation). 3 This applies to community-dwelling adults without known osteoporosis or vitamin D deficiency. 3

Implementation Framework

Deprescribing should occur within an individualized therapeutic plan understood by both patient and caregiver. 1 The process specifically targets inappropriate medications by criteria, overdosing, drug interactions, side effects, regimen simplification, adherence improvement, and cost reduction. 1

A team approach is optimal, particularly in long-term care settings, with care team members assisting in medication reconciliation, adherence assessment, and systematic identification of drug therapy problems. 1

Regular medication reviews are essential since patients taking 5 medications average 1 significant drug problem. 1 The risk of drug-related problems correlates directly with higher medication numbers. 1