Seizure Risk Up for Seniors in Nursing Homes Prescribed Tramadol and Antidepressants

Risk for seizures increased with concomitant use of tramadol with CYP2D6-inhibiting versus neutral antidepressants

By Elana Gotkine HealthDay Reporter

THURSDAY, Oct. 9, 2025 (HealthDay News) — Older adults in nursing homes (NHs) with concomitant use of tramadol and antidepressants have an increased risk for seizures, according to a study published online Oct. 8 in Neurology.

Yu-Jung Jenny Wei, Ph.D., from The Ohio State University in Columbus, and colleagues conducted a population-based cohort study using a 100 percent Medicare NH sample from January 2010 to December 2021. Long-term residents aged 65 years or older who initiated antidepressants on existing tramadol use (tramadol-antidepressant users) or initiated tramadol on existing antidepressant use (antidepressant-tramadol users) were included in the study and followed until the end of one year, NH discharge, death, or study end.

A total of 11,162 concomitant tramadol-antidepressant users and 58,994 concomitant antidepressant-tramadol users were identified. The researchers found that for the tramadol-antidepressant and antidepressant-tramadol groups, the incidence rate of seizures was 16.10 and 20.17 per 100 patient-years, respectively. The adjusted incidence rate ratios for seizures were higher with co-use of tramadol with CYP2D6-inhibiting (versus CYP2D6-neutral) antidepressants for both subgroups (1.09 and 1.06, respectively). The findings were corroborated by a negative control exposure analysis, with no risk for seizures seen in association with hydrocodone with CYP2D6-inhibiting (versus CYP2D6-neutral) antidepressants.

“These findings underscore the need for careful prescribing practices, especially for older adults with complex health conditions,” Wei said in a statement. “Doctors should be aware of potential seizure risks when prescribing tramadol with antidepressants, particularly CYP2D6 inhibitors. Given how commonly both are prescribed to older adults, these interactions may be more important than previously thought.”