Tramadol and Antidepressant Interactions May Increase Seizure Risks: Study

Certain antidepressants may interfere with how the body processes the opioid painkiller Tramadol, potentially altering its effectiveness and increasing the risk of side effects.

A new study suggests that taking the painkiller Tramadol with certain antidepressants, including Paxil and Prozac, may increase the likelihood of convulsions among nursing home residents.

According to findings published in the journal Neurology on October 8, nursing home residents who were taking Tramadol and later started an antidepressant like Paxil, which blocks a key metabolic enzyme, faced a 9% higher risk of experiencing a seizure.

Tramadol Health Risks

Tramadol is an opioid used to treat moderate to severe pain in adults. It is sold under brand names Ultram and Conzip. Health experts have warned Tramadol may pose some serious risks to users, including side effects like respiratory depression, seizures and addiction risks.

A study published by researchers from Spain and the U.K. in 2021 concluded Tramadol was linked to a higher risk of heart problems and bone fractures. Researchers said the data showed that when compared to codeine, there was also a higher risk of death.

In addition, the U.S. Food and Drug Administration (FDA) issued a warning in 2015 indicating Tramadol may cause serious breathing problems in children, including slowed breath, which could lead to severe respiratory problems, confusion and unusual sleepiness.

Another warning was issued by the FDA in 2017 stating that children should not be prescribed the opioid painkillers Tramadol and Codeine because of the serious risk of injury and death.

In the new study, researchers from Ohio State University examined how Tramadol interacts with antidepressants that inhibit the CYP2D6 enzyme, such as Prozac, Paxil, Wellbutrin and Zyban. Using 10 years of Medicare data, they analyzed records from more than 70,000 nursing home residents aged 65 and older. 

Among them, about 11,000 had been prescribed Tramadol before starting a CYP2D6-inhibiting antidepressant, while nearly 59,000 began with one of the antidepressants and later started taking Tramadol.

The research team, led by Dr. Yu-Jung Jenny Wei, concluded that using Tramadol and antidepressants like Prozac and Wellbutrin increased a person’s risk of suffering seizures, with the risk being 9% higher among people who were first taking Tramadol then started taking antidepressants. In the group who took antidepressants like Paxil first, and began taking Tramadol later, the risk was 6% higher.

In the group of participants who first started using Tramadol and then antidepressants like Prozac, the rate of seizures was 18 per 100 person years. In the group that began using antidepressants like Prozac first and then Tramadol, the rate of seizures was 22 per 100 person years.

The data showed there was an increased risk whether Tramadol was started first or the antidepressant, the research team determined. They also included a negative control group where participants used hydrocodone opioids instead of Tramadol, and still used antidepressants like Wellbutrin and Zyban. However, the team found no increased seizure risks among that group.

The researchers concluded that some CYP2D6-inhibiting antidepressants like Paxil and Prozac can interfere with how the body metabolizes Tramadol. When that happens, it can build up in the body and increase the risk of seizures.

Both Tramadol and antidepressants are commonly prescribed for older adults, so it’s especially important for doctors to factor in the risk of side effects, including seizures, when prescribing Tramadol and antidepressants together, the researchers warned.

They recommended doctors be careful when prescribing CYP2D6-inhibiting antidepressants like Paxil and Wellbutrin to older patients because of the increased risk of seizures, especially among older patients with other health conditions.

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