Polypharmacy, Drug Interactions Threaten Older Adults’ Medication Safety

As the number of medications older Americans take continues to climb, new research shows that antidepressants and muscle relaxants are quietly driving some of the most dangerous drug interactions in this vulnerable population, according to JAMA.¹

“With individuals aged 65 and older representing the fastest‐growing demographic segment, health care systems must adapt to increasingly complex medical management needs,” wrote authors of a separate study published in the Journal of Evaluation in Clinical Practice.² “Pharmaceutical interventions for older adults are no longer a simple matter of standard dosing and treatment protocols. Instead, they require a sophisticated, personalized approach that considers the intricate physiological changes accompanying aging.”

Analyzing nationally representative data from community-dwelling adults aged 62 to 85, investigators found that prescription polypharmacy (defined as taking 5 or more prescription drugs concurrently) increased from 31% during 2015-2016 to 35.7% in 2021-2023. Over the same period, dietary supplement polypharmacy also rose from 12.6% to 16.7%.^1,3

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Surging Medication Rates and Evolving Regimen Risks

Although regimens containing potentially major drug interactions experienced a modest decline from 25.7% to 22.3%, more than 1 in 5 older adults remain exposed to severe pharmacological hazards. Antidepressants (7.21%), statins (5.23%), and antiplatelet agents (4.47%) were the therapeutic classes most frequently implicated in major interaction risks.

Furthermore, despite the decrease in interacting combinations involving opioids and benzodiazepines, combinations involving muscle relaxants jumped from 1.35% to 2.49%, highlighting shifting clinical risks that could contribute to unintentional toxicity and overdose deaths.¹

Physiological Vulnerabilities and Prescribing Cascades

The danger of managing multiple drug therapies in geriatric care stems from age-related physiological changes that alter drug metabolism and sensitivity. Pharmacokinetic processes undergo significant shifts as aging reduces hepatic metabolism, renal excretion capacity, and gastric acid secretion, while simultaneously changing receptor sensitivity.^2,4

Pharmacodynamic interactions can cause additive or synergistic central nervous system depression, heightened bleeding risks, or severe sedation. In older adults managing multiple chronic health issues, providers frequently observe prescribing cascades.^2,5

A prescribing cascade occurs when side effects from one medication are misinterpreted as a new medical condition, prompting additional prescriptions that exacerbate cognitive impairment, dizziness, and fall risk. Nonprescription items also introduce substantial risk, as herbal supplements such as gingko biloba can exaggerate the actions of prescription blood thinners and trigger unexpected bleeding.⁵

Collaborative Models and Deprescribing Strategies

Community pharmacists occupy a vital position on the front lines of medication safety, frequently serving as the last defense against adverse drug events. Clinical evaluation of outpatient pharmacotherapy demonstrates that over 78% of patients experience at least one potentially clinically significant drug interaction, with patients taking an average of 5.5 prescription medications.⁴

To manage these complex regimens effectively, clinical models divide pharmacist interventions into independent actions and collaborative partnerships with physicians. Although pharmacists can independently provide patient counseling, adjust dosing intervals, and monitor side effects for moderate interactions, high-severity combinations require direct physician collaboration.

For major level D and level X interactions, collaborative models account for 97.8% to 100% of interventions to execute drug substitutions, dose adjustments, or therapy duration limits. Integrating validated tools such as the Beers Criteria and STOPP/START guidelines enables pharmacists and physicians to safely execute deprescribing protocols.^2,4,5

“Despite declines in the use of opioid analgesics and benzodiazepines in interacting regimens, increases in the use of muscle relaxants in interacting regimens may be contributing to increases in unintentional overdose deaths in older US adults,” they concluded.¹ “Therefore, efforts to identify and manage interacting regimens involving muscle relaxants among older adults are needed.”

READ MORE: LTC Pharmacy Reduces Polypharmacy, Drives Medication Adherence

REFERENCES

1. Qato DM, Wilder J, Ondanat Veetil SK, et al. Polypharmacy and drug-drug interactions among older adults. JAMA. September 24, 2026. doi:10.1001/jama.2026.17268

2. Ngcobo NN. Silent dangers in elderly pharmacotherapy: the interplay of polypharmacy, multimorbidity, and drug interactions. J Eval Clin Pract. 2025 Oct;31(7):e70283. doi: 10.1111/jep.70283

3. Harley S, Egan R. Older Americans are taking more medications, with 1 in 5 at risk for a major drug interaction. Medical Xpress. September 24, 2026. Accessed September 24, 2026. https://medicalxpress.com/news/2026-09-older-americans-medications-major-drug.html

4. Samardžić I, Marinović I, Marović I, et al. Pharmacist intervention models in drug-drug interaction management in prescribed pharmacotherapy. Pharmacy (Basel). 2025 Nov 17;13(6):167. doi: 10.3390/pharmacy13060167

5. Polypharmacy in adults 60 and older. Johns Hopkins Medicine. March 11, 2024. Accessed September 24, 2026. https://www.hopkinsmedicine.org/health/wellness-and-prevention/polypharmacy-in-adults-60-and-older