A JAMA study of nearly 5,000 U.S. adults aged 62–85 found that 22.3% faced potentially major drug-drug interactions in 2021–2023, down slightly from 25.7% in 2015–2016. Prescription polypharmacy rose from 31.0% to 35.7%, and supplement polypharmacy from 12.6% to 16.7%. Antidepressants, statins and antiplatelet drugs were most frequently involved in high‑risk combinations. Experts call for regular medication reviews, better EHR interoperability and coordinated care to reduce preventable harm for older adults.
More Than One in Five Older Americans Face Potentially Dangerous Drug Interactions, Study Finds
Medical supplies on a bedside table.
A new JAMA study finds that more than one in five older Americans are taking combinations of prescription medicines and dietary supplements that could produce potentially major drug-drug interactions — a risk that, while slightly reduced in recent years, remains widespread.
What the study examined
Researchers analyzed nationally representative data from nearly 5,000 U.S. adults aged 62 to 85 drawn from the National Social Life, Health and Aging Project, supported by the National Institute on Aging. The team compared medication and supplement use in 2015–2016 with use in 2021–2023.
Key findings
The study reports that prescription polypharmacy (defined as taking five or more prescription medicines simultaneously) rose from 31.0% in 2015–2016 to 35.7% in 2021–2023. Dietary supplement polypharmacy increased from 12.6% to 16.7% over the same period. Although the share of older adults exposed to potentially major drug-drug interactions declined from 25.7% to 22.3%, more than one in five remained at risk in 2021–2023.
Medications Most Often Involved
Antidepressants, statins and antiplatelet therapies were the medication classes most commonly appearing in high‑risk combinations. Study authors and independent clinicians note that these drug classes are widely used and often medically necessary, which complicates efforts to eliminate risky pairings.
"Patients who have several chronic illnesses are inevitably treated with complicated regimens," said Dr. Spencer Kroll, a physician with expertise in pharmacology. He added that while the slight decline in high‑risk interactions is encouraging, the persistence of elevated risk in more than one‑fifth of older adults poses a major public health challenge, particularly in geriatric care.
Why this matters
Each additional medication increases pharmacokinetic and pharmacodynamic complexity in older bodies, raising the likelihood of adverse effects, reduced drug metabolism, increased toxicity and unplanned hospitalizations. Fragmented care — with multiple prescribers, pharmacies and poorly interoperable electronic health records — contributes to missed opportunities for comprehensive medication review.
Recommendations
Lead author Dima Mazen Qato and colleagues emphasize the need for stronger medication-safety efforts that target commonly used interacting regimens, especially those involving antidepressants. Experts recommend regular, comprehensive medication reviews, improved EHR interoperability, pharmacist involvement in care teams, and careful risk–benefit assessments when adding or continuing therapies in older adults.
Study citation: Qato D.M., Wilder J., Ondanat Veetil S.K., et al. (2026). Polypharmacy and Drug-Drug Interactions Among Older Adults. JAMA. doi: 10.1001/jama.2026.17268.
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