A common mix of medications prescribed in nursing homes may raise the risk of seizures in older adults, according to a new study.

The study, published in Neurology, the journal of the American Academy of Neurology, analyzed prescription and health records from more than 70,000 long-term care residents.

About one in five nursing home residents who took tramadol with certain antidepressants such as Prozac, Wellbutrin, and similar medications had a seizure within a year. That is more than 10 times the risk typically seen in this population.

The drug combination is not uncommon in long-term care. Tramadol, an opioid, is prescribed for pain, and up to 60 percent of nursing home residents take antidepressants.

Yu-Jung “Jenny” Wei, the study’s lead author and a pharmacoepidemiologist at The Ohio State University College of Pharmacy, told The Epoch Times in an email that these results are a reminder for doctors, patients, and caregivers to pay attention to the risk of seizures when older adults are taking both tramadol and certain antidepressants.

A Closer Look at the Drug Interaction

Both tramadol and certain antidepressants can raise the risk of seizures in older adults. However, it is the combination of the two that makes the difference, according to the study.

Tramadol has long raised concerns because of its known seizure risk in older adults, and when paired with antidepressants that block a specific enzyme, the danger goes up even more.

“Some of these medications—like bupropion—have been known to increase seizure risk by themselves,” Dr. Christopher Elder, a neurologist at NYU Langone Health who was not involved in the study, told The Epoch Times.

“But what’s new here is the evidence that combining them with tramadol makes the risk even higher.”

Researchers analyzed 10 years of Medicare and nursing home health data, focusing on residents aged 65 and older who started taking tramadol and an antidepressant at the same time or within a few weeks of each other.

Among those treated with the drug combination, 18 to 22 of every 100 residents had a seizure within one year, compared with fewer than two per 100 in the general nursing home population.

Researchers adjusted for more than 40 health variables such as age. Still, they said this was an observational study showing association, not proof of causation.

The increased risk appears to be linked to how these drugs interact in the body. Tramadol is usually broken down by a liver enzyme called CYP2D6. However, certain antidepressants block this enzyme, causing tramadol to accumulate and raising the chance of side effects such as confusion, tremors, or seizures.

The antidepressants most associated with this elevated risk included:

• Fluoxetine (Prozac) and Paroxetine (Paxil): Both selective serotonin reuptake inhibitors


• Duloxetine (Cymbalta): Often used for pain and anxiety


• Bupropion (Wellbutrin): Also used for smoking cessation or seasonal depression


• Doxepin: A tricyclic antidepressant sometimes used in low doses for sleep

These medications are often prescribed to older people for depression, as well as for conditions such as nerve pain, sleep disturbances, and anxiety, which may make their interaction with tramadol less obvious to patients and caregivers, according to Elder.

Who Is Most at Risk

Seizure risk peaks at both ends of life. Risk is highest in infancy and old age and is lowest in between, according to Elder. For nursing home residents, those later years can bring new vulnerabilities, especially when health problems or multiple medications are in the mix.

In the study, the risk was most pronounced among women and non-white residents. People with dementia or heart disease faced higher odds as well.

Tramadol is not a typical opioid; it also increases levels of serotonin and norepinephrine, much like antidepressants do. When tramadol builds up in the bloodstream because of CYP2D6 inhibition, its effects on brain chemistry can intensify.

That makes side effects such as seizures more likely, especially in people who are already vulnerable.

Notably, the seizure risk did not rise when these same antidepressants were combined with hydrocodone, a different opioid broken down by other enzymes. That contrast suggests that the risk lies in tramadol’s unique metabolism and its additional effects on brain chemicals such as serotonin and norepinephrine, neurotransmitters that help regulate mood, alertness, and nerve signaling.

Should Tramadol Still Be Used in Older Adults?

“[The study] gives further support for not using tramadol for pain management and using alternative options for pain control,” Elder said.

For older adults who may be taking tramadol with a CYP2D6-inhibiting antidepressant, the findings may be a reason to revisit the medication plan. Adjustments such as switching to a different antidepressant or using another pain reliever could help reduce seizure risk.

This is particularly relevant for nursing home residents, who often deal with multiple health issues and take several medications.

Neurologists generally try to avoid prescribing tramadol in these settings and for anyone with seizure risks, Elder said, but awareness can vary outside of specialty care.

Even in general pain management, tramadol is no longer a first-line option, yet about 13 percent of nursing home residents still receive it.

Although more studies are needed, the authors concluded that the tramadol and antidepressant combination deserves closer scrutiny.