Post-traumatic epilepsy (PTE) is common, occurring in upward of 1 in 3 patients with severe traumatic brain injury (TBI). There are limited data regarding initial prescription patterns and long-term course of antiseizure medications (ASMs).

The goal of this study was to describe ASM prescription patterns and pharmacoresistance over time. We performed a secondary analysis of a prospective database of patients with severe TBI treated at a single center from 2002 through 2018. We included patients with PTE, defined as at least one seizure more than 7 days from injury, and at least six-month follow-up after PTE onset. ASMs were categorized as older (e.g., phenytoin) or newer (e.g., levetiracetam). We evaluated ASM prescription patterns and their association with epileptology referral and Glasgow Outcome Scale (GOS) score. We developed a logistic regression to predict pharmacoresistance.

Our cohort included 84 patients with PTE. ASM prescription for longer than 7 days after injury had only moderate correspondence with early post-traumatic seizures or PTE (Cohen Kappa 41%). At PTE onset, most (53%) were treated with newer ASM monotherapy, with 27% on older ASMs and 20% on multiple ASMs. Patients initially prescribed older ASM monotherapy were less likely to maintain their ASM monotherapy (e.g., medication switch/addition and self-wean) compared with those on newer ASMs (odds ratio [OR] 4.6; 95% confidence interval [CI] 1.3-16.7; p = 0.02). Only 23% of patients were referred to specialized epilepsy care despite 54% trialing 2 or more ASMs. Pharmacoresistance was associated with worse GOS outcomes (p = 0.04). Decompressive hemicraniectomy (OR 6.0; 95% CI 1.4-44; p = 0.03) and initial ASM polytherapy (OR 7.2; 95% CI 1.7-34; p < 0.01) predicted pharmacoresistance at 2 years.

We provide evidence suggesting that use of newer generation seizure medications is preferable when treating PTE. In addition, we identified early risk factors of pharmacoresistance, which was associated with poor long-term outcomes.