Possible Drug-Drug Interactions Flagged for Older Americans

More work is needed with regard to antidepressants and muscle relaxants amid efforts to tamp down on polypharmacy and harmful drug-drug interactions, according to nationally representative data.

Among Americans ages 62 and older, there was no change in the use of prescription medications (84.2% vs 84.8%, P=0.60) and use of dietary supplements (65.6% vs 66.8%, P=0.44) between 2015-2016 and 2021-2023.

On the rise, however, was polypharmacy involving prescription medications (31.0% vs 35.7%, P=0.003) and dietary supplements (12.6% vs 16.7%, P=0.001).

The good news was that the proportion of people with potentially major interacting drug regimens or drug-drug interactions fell through the years (25.7% vs 22.3%, P=0.02), driven by a drop in interacting regimens involving prescription medications (24.5% vs 21.9%, P=0.07), according to a group led by Dima Qato, PharmD, MPH, PhD, of the University of Southern California in Los Angeles.

Of note, potentially major drug-drug interactions still most commonly involved antidepressants, and there was a rise in the use of interacting regimens involving muscle relaxants (1.35% vs 2.49%, P=0.03), the investigators reported in JAMA.

“Efforts aimed at reducing polypharmacy and adverse drug events from drug-drug interactions, including deprescribing initiatives and guidelines, should prioritize interacting regimens commonly and persistently used among older U.S. adults,” study authors wrote.

“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 U.S. adults. Therefore, efforts to identify and manage interacting regimens involving muscle relaxants among older adults are needed,” Qato’s group urged.

The researchers also stressed safer use of antidepressants, known to have associations with increased risk of serotonin syndrome and/or arrhythmias.

“Treatment guidelines for depression in older adults and initiatives aimed at deprescribing psychotropic medications should prioritize drug-drug interactions involving antidepressants and increase awareness of the serotonergic and cardiovascular risks associated with their use,” Qato and colleagues suggested.

The study was based on the National Social Life, Health, and Aging Project, a nationally representative, population-based sample of community-dwelling adults age 62-85 in the U.S. From Wave 3 (2015-2016) and Wave 4 (2021-2023), investigators had 2,754 (mean age 70.2 years) and 2,186 (mean age 70.8 years) individuals, respectively, with medication records for analysis.

Medication use was defined as regular (daily or weekly) use of at least one prescription or over-the-counter (OTC) medication or dietary supplement. Polypharmacy was defined as concurrent use of at least five medications or supplements.

Unlike prescription drugs and dietary supplements, the use of OTC medications declined from 2015-2016 to 2021-2023 (60.1% vs 55.1%, P=0.04), Qato and colleagues reported.

The Cerner-Multum Lexicon Plus database was used to identify potentially major drug-drug interactions. From this, the study authors found that the general profile of potentially major drug-drug interactions among older adults remained unchanged throughout the study period. Antidepressants (7.21%), statins (5.23%), and antiplatelet therapy (4.47%) remained the most common among these interacting regimens in 2021-2023.

In contrast, there were declines in interacting regimens involving opioid analgesics (5.56% vs 4.04%, P=0.03) and benzodiazepines (2.05% vs 0.87%, P=0.003).

The study was not able to identify actual adverse drug events from drug-drug interactions, Qato’s team cautioned. Another major study limitation was the lack of data on patient-level factors that may influence the risk of adverse drug events.