Pain and antidepressant drug combo linked to increased seizure risk in older adults (Tramadol)

Medical Xpress / American Academy of Neurology / Neurology ^ | Oct. 8, 2025 | Yu-Jung Jenny Wei, Ph.D. et al

[ConservativeMind]

When older adults living in nursing homes are prescribed the pain medicine tramadol alongside certain antidepressants, their risk of seizures may go up, according to a study. While this study found a link, it does not prove one causes the other.

Tramadol is an opioid used to treat moderate to severe pain in adults. Some antidepressants that inhibit the CYP2D6 enzyme, called CYP2D6 inhibitors, can interfere with how the body metabolizes tramadol. When the CYP2D6 enzyme is blocked, tramadol is not metabolized properly and may build up in the body, potentially increasing the risk of side effects like seizures. Common CYP2D6-inhibiting antidepressants include fluoxetine, paroxetine and bupropion.

Researchers analyzed 10 years of Medicare data to identify 70,156 nursing home residents age 65 and older who had been prescribed both tramadol and an antidepressant.

Seizure rates for people who took tramadol first were 16 seizures per 100 person-years, and for people who took antidepressants first, the rate was 20 seizures per 100 person-years.

Researchers then compared seizure rates between those who took tramadol with CYP2D6-inhibiting antidepressants and those who took tramadol with antidepressants that do not inhibit the enzyme. In those who took tramadol first and added an antidepressant, the rate was 18 seizures per 100 person-years for those taking CYP2D6-inhibiting antidepressants compared to 16 seizures per 100 person-years in people taking other antidepressants.

In those who took antidepressants first and added tramadol, the rate was 22 seizures per 100 person-years for those taking CYP2D6-inhibiting antidepressants compared to 20 seizures per 100 person-years in people taking other antidepressants.

To test whether this interaction was specific to tramadol, the researchers repeated the analysis using hydrocodone, another opioid pain reliever that is unlikely to cause seizure risk when used with antidepressants. No increased seizure risk was observed with hydrocodone and CYP2D6-inhibiting antidepressants.

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TOPICS: Health/Medicine
KEYWORDS: jamitol; tramadol

[ConservativeMind]

I’d stay away from tramadol, but note this study shows an association, but it seems reasonable.

For every year, there appears to be a 16-22% likelihood of seizures, regardless of antidepressant, with tramadol.

[ConservativeMind]

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[sauropod]

Bkmk

[HollyB]

I don’t think there’s even opioids in tramadol. It’s how it works in the brain. Seems Anti-depressants taken with tramadol may lead to serotonin syndrome ?
But, I agree with you, it’s a med one shouldn’t take unless it’s for a short time.

[kawhill]

When I see these ads for a drug and they say: “Don’t take this medicine if you’re allergic to it”, I think that might be a good idea, but how does one know beforehand?

[OftheOhio]

Thanks! I had a horrible case of gout this last week in my left ankle. I thought about taking some Tramadol I had a script for, but decided against it. The Colchicine I took was bad enough. At least I can stand on it now.

[catnipman]

in addition to being a semi-synthetic opioid, tramadol also has powerful SNRI anti-depressant effects as well; thus combining with ANOTHER anti-depressant doesn’t sound like a great idea ...

[catnipman]

tramadol is a semi-synthetic opioid with powerful SNRI anti-depressant effects as well ... it’s addictive like all opioids ...

[Rad_J]

Tramadol works great for me. It’s the only prescription pain medication that has ever taken away the pain. Most just make me loopy and make me not care about the pain. I took it sparingly after an auto accident. I have no side effects. My wife took some for an injury and it makes her sleep a long time and she doesn’t like how it makes her feel.

[Flaming Conservative]

When I injured my back at work, the worker’s comp doctor prescribed tramadol. Might as well have prescribed a placebo. It did absolutely nothing for my pain. My regular doctor prescribed Norco, which is a true opioid. I took very little of it, (thank God I don’t have an addictive personality) but at least it relieved my pain. I still have a script for it. It takes me about 2 1/2 years to use up a 7 day supply.

[gitmo]

I take Tramadol every once in a blue moon. I think I’ll wait for more studies before taking any more.

[gitmo]

Tramadol does nothing for my wife. When I take it, I can feel it hit about 15 minutes later. I get a distinct buzz, and it stops my pains.

[OftheOhio]

I’ve always wondered about medicine effects based on the various blood types. One wonders if that is even part of the testing for establishing trials.

[Pearls Before Swine]

For every year, there appears to be a 16-22% likelihood of seizures, regardless of antidepressant, with tramadol.

How does that square with the text stating that the differential is 22 versus 20 per 100 person years?

BTW, I never thought tramadol was a terribly effective pain reliever, anyway.