Neurology

Tramadol-antidepressant combo linked to elevated seizure risk in older adults

October 15, 2025

Study details: This population-based cohort study analyzed 70,156 long-term nursing home residents (mean age, ~86 years; >80% female) from a 100% Medicare nursing home sample (2010–2021) who initiated tramadol and antidepressants either concurrently or sequentially. The primary exposure was tramadol co-administered with CYP2D6-inhibiting vs. CYP2D6-neutral antidepressants. Outcomes were incident medical encounters for seizures, adjusted for baseline pain, depression, and functional status.

Results: Seizure incidence rates were 16.10 seizures per 100 patient-years when tramadol was started first, and 20.17 per 100 patient-years when the antidepressant was started first. In both groups, co-use with CYP2D6-inhibiting antidepressants was associated with a modest but statistically significant increase in seizure risk compared with CYP2D6-neutral antidepressants. The adjusted incidence rate ratio was 1.09 (95% confidence interval [CI], 1.02–1.18) for the tramadol-first group and 1.06 (95% CI, 1.03–1.10) for the antidepressant-first group. No increased risk was found when tramadol was replaced with hydrocodone.

Clinical impact: The findings highlight the importance of cautious prescribing in older adults, especially when combining tramadol with CYP2D6-inhibiting antidepressants. Clinicians should consider alternative pain management strategies and review medication interactions to mitigate seizure risk in this vulnerable population.

Source:

Wei YJ, et al. (2025, November 11). Neurology. Risk of Seizure Associated With Concomitant Use of Tramadol and Antidepressants in Older Nursing Home Residents. https://pubmed.ncbi.nlm.nih.gov/41061201/