Tramadol and seizures: a surveillance study in a managed care population

Study Objective. To investigate the occurrence of tramadol-associated seizures. Design. Retrospective cohort and case-control studies. Setting. UnitedHealth Group-affiliated independent practice model health plans, from different regions of the United States, contracting with large networks of physicians. Intervention. Analysis of administrative data from a large U.S. managed care population. Patients. A cohort of 9218 adult tramadol users and 37,232 concurrent nonusers. Measurements and Main Results. Fewer than 1% of users (80) had a presumed incident seizure claim after the first tramadol prescription. Risk of seizure claim was increased 2- to 6-fold among users adjusted for selected comorbidities and concomitant drugs. Risk was highest among those aged 25–54 years, those with more than four tramadol prescriptions, and those with history of alcohol abuse, stroke, or head injury. A case-control study among users was conducted to validate incident seizure outcomes from medical records. Only eight cases were confirmed, and all had cofactors associated with increased seizure risk. Conclusion. In a general population, risk of seizure may be associated with long-term therapy with tramadol or the presence of cofactors, or confined to a small sensitive population subset.