Increased Seizure Risk in Older Adults with Pain and Antidepressant Combo

Recent research indicates that combining certain pain medications with antidepressants may elevate the risk of seizures among older adults living in nursing homes. A study published in Neurology analyzed over a decade of Medicare data, involving more than 70,000 residents aged 65 and above, to explore the effects of this medication combination. The findings revealed that when tramadol, a commonly used opioid for moderate to severe pain, was prescribed alongside specific antidepressants that inhibit the CYP2D6 enzyme, the likelihood of seizures increased.

Tramadol’s metabolism relies heavily on the CYP2D6 enzyme. Antidepressants such as fluoxetine, paroxetine, and bupropion inhibit this enzyme, potentially causing tramadol to accumulate in the body and heighten side effects like seizures. The study observed that residents who started with tramadol and later added an antidepressant faced a seizure rate of 16 per 100 person-years, whereas those who began with an antidepressant and added tramadol had a rate of 20 per 100 person-years.

Further analysis showed that meal providers taking CYP2D6-inhibiting antidepressants alongside tramadol experienced a slight but significant increase in seizure risk—about 9% more when tramadol was taken first, and 6% more when antidepressants were initiated first. Notably, the study also tested hydrocodone, another opioid, and did not find a similar increase in seizure risk when combined with these antidepressants, indicating the specific interaction between tramadol and CYP2D6 inhibitors.

These findings highlight the importance of cautious prescribing, especially for older adults with complex health conditions. Healthcare providers should be vigilant about the potential for increased seizure risk when combining tramadol with certain antidepressants. Since both medication types are frequently prescribed for older populations, understanding this interaction is crucial for safer treatment approaches.

It is important to note that the study relied on prescription records, which do not confirm actual medication intake, representing a limitation. Nonetheless, this research emphasizes tailored prescribing practices to mitigate risks and promote patient safety.

Source: https://medicalxpress.com/news/2025-10-pain-antidepressant-drug-combo-linked.html