In this episode of Hospital Medicine Unplugged, we tackle polypharmacy and deprescribing—how to recognize problematic medication overload, quantify its harms, and apply structured, patient-centered strategies to safely reduce medication burden.

We begin with definitions that shape clinical practice. Polypharmacy is most commonly defined as the use of ≥5 medications, though definitions vary. Importantly, not all polypharmacy is harmful. “Appropriate polypharmacy” occurs when medications are evidence-based and optimized, while “problematic polypharmacy” arises when medications lack clear benefit or when harms outweigh benefits. Deprescribing is the systematic process of identifying and discontinuing medications whose risks exceed benefits, aligned with a patient’s goals, function, life expectancy, and preferences.

Next we review how common this problem is. Polypharmacy affects 30–40% of community-dwelling older adults, 40–50% of hospitalized older adults, and up to 90% of nursing home residents. Roughly 20–50% of older adults take at least one potentially inappropriate medication (PIM). Risk rises with multimorbidity, female sex, lower socioeconomic status, and each additional chronic disease increases the odds of polypharmacy by nearly 90%.

We then quantify the clinical consequences. • Adverse drug events occur in 20–30% of hospitalized older adults, and each additional medication increases adverse reaction risk by ~10%. • Polypharmacy is associated with higher mortality (HR ~1.2–1.7) and increased hospital admissions and readmissions. • It also increases fall risk (OR ~1.6) and contributes to hip fractures, frailty, cognitive impairment, and functional decline.

A key driver is the prescribing cascade, where a drug causes side effects that are treated with additional medications. Classic examples include: • NSAIDs → hypertension → antihypertensives • Cholinesterase inhibitors → urinary incontinence → anticholinergics • Calcium channel blockers → edema → diuretics • Antipsychotics → parkinsonism → antiparkinsonian drugs

To identify problematic medications, we review major screening tools. • 2023 AGS Beers Criteria highlights medications to avoid or use cautiously in older adults, including guidance on benzodiazepines, antipsychotics in dementia, and aspirin for primary prevention in adults ≥70. • STOPP/START version 3 includes 94 criteria for inappropriate prescriptions and 34 for underprescribing. • Additional tools include the Medication Appropriateness Index, FORTA classification, Anticholinergic Cognitive Burden scale, and Drug Burden Index.

We then walk through a practical deprescribing framework. A common 5-step protocol includes:

1. List all medications and indications

2. Assess overall risk of drug-related harm

3. Identify drugs eligible for discontinuation

4. Prioritize those with highest harm and lowest benefit

5. Implement tapering and monitor for withdrawal or recurrence

Certain medications require careful tapering to prevent withdrawal syndromes, including benzodiazepines, beta-blockers, antidepressants, corticosteroids, opioids, antiepileptics, clonidine, baclofen, and proton pump inhibitors.

We highlight high-yield deprescribing targets. • Proton pump inhibitors: up to 70% lack appropriate indication; associated with C. difficile infection, pneumonia, CKD, and fractures. • Benzodiazepines: linked to falls, delirium, and cognitive impairment, with tapering success rates 27–80%. • Antipsychotics: frequently used for dementia behaviors but carry 1.6–1.7× increased mortality risk. • Anticholinergic medications: high burden strongly linked to cognitive decline and mortality. • Sliding-scale insulin: increases hypoglycemia without improving glycemic control.

We also discuss patient and system barriers. Interestingly, 92% of older adults say they would stop at least one medication if their doctor recommended it, though many fear symptom recurrence or believe medications are necessary.

Finally, we examine solutions that work. Pharmacist-led medication reviews reduce inappropriate medications by 21–35% and lower readmissions, while clinical decision support tools in electronic health records can flag high-risk medications and prompt deprescribing conversations.

The takeaway: polypharmacy is common, harmful, and often reversible. Using structured frameworks, validated screening tools, and shared decision-making, clinicians can safely deprescribe and improve medication safety—especially for older adults with multimorbidity.