Concomitant use of tramadol and antidepressants with potent inhibition of the cytochrome P450 2D6 (CYP2D6) enzyme is postulated to increase risk of seizures in older adults; yet, such an association has not been empirically tested in populations. The study aimed to examine the association of concomitant tramadol and CYP2D6-inhibiting vs CYP2D6-neutral antidepressant use and the risk of seizures among older nursing home (NH) residents.