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.