More than 1 in 5 older Americans take drug combinations that risk a major interaction, and antidepressants turn up in them most often.
Most older Americans take at least one prescription drug every week, and a growing share now take five or more at the same time.
With each added pill comes another chance for two of them to interact.
Across the country, a new analysis of national survey data estimates that more than 1 in 5 older adults were taking a combination that risks a major drug interaction.
That share has dropped a little since the mid-2010s. The drugs most often involved barely changed, though, and antidepressants led the list.
These are potential interactions, and the researchers counted how many people were taking risky pairings. Whether anyone was harmed by them wasn’t part of the study.
Dima Mazen Qato, an associate professor of clinical pharmacy at the USC Mann School of Pharmacy and Pharmaceutical Sciences, led the work.
She’s also a senior fellow at USC’s Schaeffer Center for Health Policy & Economics. Her co-authors came from the Johns Hopkins Bloomberg School of Public Health and NORC at the University of Chicago.
Five or more drugs grew more common
The team drew on the National Social Life, Health, and Aging Project, a long-running survey of adults ages 62 to 85 who live at home instead of in nursing homes. It’s designed to represent that whole age group across the country.
Researchers compared 2,754 people surveyed in 2015 and 2016 with 2,186 surveyed between 2021 and 2023. Anyone who used a product daily or weekly counted as a regular user.
Some habits held steady. About 85% of older adults took at least one prescription drug in both periods, and about two-thirds took a dietary supplement.
Regular use of over-the-counter medicines, the kind bought off the shelf like ibuprofen or aspirin, slipped from 60.1% to 55.1%. What changed most was how many prescriptions people took at once.
Taking five or more at the same time is what researchers call polypharmacy. Among these older adults, prescription polypharmacy rose from 31.0% to 35.7%, and the share taking five or more supplements climbed from 12.6% to 16.7%.
So about the same share of people were on prescriptions as before. More of those people, though, were juggling a long list of them.
Risky pairings fell only a little
To flag a dangerous pairing, the team ran each person’s medicines through a drug-interaction database.
They counted only the most serious category, combinations rated highly clinically significant, where the risk of the interaction outweighs the benefit.
By that measure, 25.7% of older adults were taking at least one potentially major interacting combination in 2015 and 2016.
By 2021 to 2023, the figure was 22.3%, and most of the drop came from combinations involving prescription drugs.
That’s progress, but not much of it. Among 10 people that age, about two would still be taking a risky pairing.
The authors pointed to why that matters.
Between 2015 and 2025, the U.S. Food and Drug Administration received reports of roughly 63,000 serious problems attributed to drug interactions in adults 65 and older, and about 10% of them were fatal.
Antidepressants showed up most often
In 2021 to 2023, antidepressants were the drug class most often involved in a potentially major interaction, at 7.2% of older adults.
Statins, the cholesterol-lowering drugs, came next at 5.2%, followed by blood-thinning antiplatelet drugs such as aspirin at 4.5%.
For all three, the change between the two surveys was small enough to be chance. The same drugs stayed at the top.
The authors singled out antidepressants for a reason.
In some of those combinations, antidepressants are linked to a reaction that leaves the body with too much serotonin, a chemical that acts as a neurotransmitter.
Doctors call it serotonin syndrome. Others are tied to heart rhythm problems.
“These findings underscore the need for continuing efforts to improve medication safety among older adults,” Qato said.
“Efforts to reduce polypharmacy and harmful drug interactions should focus on commonly used interacting regimens, particularly those involving antidepressants.”
Opioids fell, muscle relaxants rose
A few drug classes did shift. Opioid painkillers turned up in fewer risky combinations, dropping from 5.6% of older adults to 4.0%, and benzodiazepines, a class of sedatives, fell from 2.1% to 0.9%.
Not every class followed that path. Muscle relaxants in risky combinations nearly doubled, from 1.4% to 2.5%.
The authors suggested that this rise may be contributing to the increase in accidental overdose deaths among older adults in the United States.
They called for more work to identify and manage combinations that include muscle relaxants.
Actual harm was not measured
Only the products people took were recorded, not what happened to them afterward. The authors noted that they had no data on actual harm from these interactions.
They also lacked details about each person that might raise or lower the danger of a given pairing.
Milder interactions weren’t counted, so the tally covers only the most serious kind.
For people worried about serotonin syndrome, MedlinePlus – the National Library of Medicine’s consumer health site – advises talking to a health care provider before stopping any medicine.
How many of these combinations actually hurt the people taking them is still an open question. The authors want programs that help patients cut back on medicines to focus first on the interacting combinations people take most.
They asked the same of depression treatment guidelines for older adults, with antidepressant combinations at the top of the list.
NORC has kept collecting survey data since 2024, so a later round could show whether the share at risk keeps falling.
The full study was published in the journal JAMA.
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