Title: Evaluation of Guideline-Recommended Duration of Levetiracetam Prophylaxis Prescribed in Patients After Traumatic Brain Injury
Authors: Michael Kim, Kameron Hicks, Rachel Friend, Donley Galloway
Background: Traumatic brain injuries (TBI) may lead to early post-traumatic seizures (PTS), especially in instances of severe TBI and to a lesser extent in mild to moderate TBI. Early PTS are mechanistically distinct from late PTS and most often occur within seven to fourteen days of the inciting TBI. They are associated with poor morbidity and mortality outcomes. Recent guidelines by the Neurocritical Care Society suggest that there is no statistical difference in the reduction of early seizures with or without the use of antiseizure medications. However, levetiracetam is commonly used as seizure prophylaxis due to its favorable adverse drug effect profile. The use of antiseizure medications for a shorter duration of time of ≤ 7 days is recommended because the studies have identified no statistical difference with longer duration of antiseizure medication therapy and worse adverse effect incidence. As the use of prophylactic levetiracetam provides limited benefits in preventing early seizures, the purpose of this study is to evaluate its current prescribing practices to potentially provide evidence to support standardized as lengthy duration and high dose is not well supported by current evidence.
Methods: This was an IRB approved single-centered, retrospective evaluation of adult patients diagnosed with traumatic brain injury and given levetiracetam as seizure prophylaxis who were admitted to one of four inpatient neurologic or trauma units between June 1, 2025, to May 31, 2025. Patients were excluded if they had any prior history of seizures, on any maintenance antiepileptic medications, used any other antiepileptic medications for seizure prophylaxis, or were prisoners. The primary outcome of this study was the rate of guideline recommended duration of levetiracetam prophylaxis. Secondary outcomes included documented seizure activity within the encounter, dose and frequency of levetiracetam used as prophylaxis, number of patients discharged home with levetiracetam, and any documented CNS or hypersensitivity reactions from levetiracetam. The collected data was analyzed using descriptive statistics and chi-square test.
Results: A total of 111 patients were included. The rate of guideline recommended duration of levetiracetam for seizure prophylaxis after TBI was 43.2% (n=48/111. The rate of guideline directed duration of therapy in just the inpatient days of prophylactic therapy yielded 82% (n=91/111). Within the subgroups, the rate of guideline directed duration of therapy was 47.4% (n=27/57) in the STICU, 48.6% (n=17/35) in the NICU, 18.2% (n=2/11) in E5, and 25% (n=2/8) in E4. The frequency of the maintenance prophylaxis was twice daily dosing. The doses administered inpatient were varied, but was most commonly 500 mg twice daily (63.1%, n=71/111). The number of those discharged on levetiracetam was 51.4% (n=57/111) with durations ranging from 1-90 days and doses ranging from 500mg-1000mg. Possible CNS effects from levetiracetam was seen in 21 patients (18.9%). One patient (0.9%) had evidence of seizure activity.
Conclusions: Guideline recommended duration of levetiracetam as early post-traumatic seizure prophylaxis was seen in less than half of the patients within this institution’s main trauma and neurologic units when accounting for both initial inpatient and outpatient continuation of prophylactic therapy. Most patients in the inpatient setting received the recommended duration of therapy of seven days or fewer, but prescription orders at discharge for prophylaxis up to 90 days were observed. With the only seizure having been seen in the severe TBI patient, potential adverse drug effects seen, and long duration of prophylaxis that the majority of these patients received, more conservative management with seizure prophylaxis may be warranted. Future studies that evaluate the seizure incidence between evidence supported shorter duration of therapy and extended duration of therapy may contribute to the potential de-prescribing efforts of pharmacists.
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