Major Drug Interactions Decline Among Older Adults, but Risks Persist

• A cross-sectional analysis examined changes in medication and dietary supplement use in the United States from 2015-2016 to 2021-2023.
• Polypharmacy involving prescription drugs or dietary supplements increased during the study period.
• Potentially major drug interactions became less common but still affected more than one in five older adults.

Prescription antidepressants and muscle relaxants warrant further attention as health systems work to reduce polypharmacy and harmful drug-drug interactions, according to nationally representative data.

Among Americans aged 62 and older, use of prescription medications did not change significantly between 2015-2016 and 2021-2023 (84.2% vs 84.8%, P=0.60). Use of dietary supplements also remained largely stable (65.6% vs 66.8%, P=0.44).

Polypharmacy increased in both categories. The share of older adults concurrently using at least five prescription medications rose from 31.0% to 35.7% (P=0.003), while the corresponding figure for dietary supplements increased from 12.6% to 16.7% (P=0.001).

There was a modest decline in potentially major drug-drug interaction regimens, from 25.7% to 22.3% (P=0.02). Interactions involving prescription medications also decreased, although not significantly, from 24.5% to 21.9% (P=0.07). The findings come from a research group led by Dima Qato, PharmD, MPH, PhD, of the University of Southern California in Los Angeles.

Antidepressants remained the medications most frequently associated with potentially major interactions. At the same time, interacting regimens that included muscle relaxants increased from 1.35% to 2.49% (P=0.03), the investigators reported in JAMA.

The authors said deprescribing programs and clinical guidelines should focus on medication combinations that older adults commonly use and that persist over time.

Although interacting regimens containing opioid pain relievers and benzodiazepines became less common, their growing use with muscle relaxants may be adding to unintentional overdose deaths among older Americans. Qato and colleagues called for better identification and management of prescriptions that combine these drugs.

The researchers also emphasized safer prescribing and monitoring of antidepressants, which may be associated with serotonin syndrome and arrhythmias.

Depression-treatment guidelines and psychotropic deprescribing initiatives should give greater attention to antidepressant-related interactions, as well as their serotonergic and cardiovascular risks, they advised.

The analysis used data from the National Social Life, Health, and Aging Project, a nationally representative, population-based study of community-dwelling adults aged 62-85 in the United States. Researchers analyzed medication records from 2,754 participants in Wave 3 (2015-2016; mean age, 70.2 years) and 2,186 participants in Wave 4 (2021-2023; mean age, 70.8 years).

Medication use was defined as regular daily or weekly use of at least one prescription drug, over-the-counter product, or dietary supplement. Polypharmacy meant the concurrent use of at least five such products.

Unlike prescription drugs and dietary supplements, over-the-counter medication use declined from 60.1% in 2015-2016 to 55.1% in 2021-2023 (P=0.04).

The researchers used the Cerner-Multum Lexicon Plus database to identify potentially major drug-drug interactions. The overall interaction profile remained stable during the study period. In 2021-2023, antidepressants (7.21%), statins (5.23%), and antiplatelet therapy (4.47%) remained the most common components of interacting regimens.

By contrast, interaction regimens involving opioid analgesics declined from 5.56% to 4.04% (P=0.03), and those involving benzodiazepines fell from 2.05% to 0.87% (P=0.003).

The study could not determine whether specific drug interactions caused adverse drug events. The researchers also noted that the dataset lacked patient-level information that could influence the risk of harm.

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