Neuropsychiatric Events With Levetiracetam for Seizure Prophylaxis Following Traumatic Brain Injury

Introduction: Levetiracetam (LEV) is a soluble ethyl analogue of the nootropic agent piracetam that is utilized primarily for epilepsy treatment. LEV has preferred pharmacokinetic and pharmacodynamic properties and a more favorable safety profile than alternative pharmacotherapy options, however; the incidence of neuropsychiatric events is a potential concern. The objective of this study was to evaluate the incidence of neuropsychiatric events in patients receiving levetiracetam for seizure prophylaxis following a traumatic brain injury (TBI).


Methods: This retrospective cohort analysis conducted at a Level II trauma, academic medical center between January 1, 2023, and March 15, 2025. Inclusion criteria were patients 18 years and older who had been admitted to the surgical intensive care unit (SICU) and received levetiracetam for seizure prophylaxis following a TBI. The primary study outcome was to assess the incidence of neuropsychiatric events attributed to levetiracetam. Secondary outcomes included levetiracetam dose/route, seizure occurrence, time to onset of neuropsychiatric event, SICU length of stay and duration of levetiracetam treatment.


Results: There were 55 patients included in the study. The mean age of patients was 61 years, the mean weight was 79 kg, median Glasgow Coma Score was 14, and the median Rotterdam CT score was 3. Regarding the primary endpoint, two patients (3.6%) experienced a neuropsychiatric event. There were 14 patients (25.5%) with a history of previously diagnosed psychiatric disorders, of whom only one experienced a neuropsychiatric event while receiving LEV. The majority of patients received a LEV dose of 750 mg twice daily, either by mouth or intravenously. 12 patients (21.8%) experienced a seizure while receiving LEV for primary prophylaxis following their TBI. The mean length of SICU stay was 5 days, and LEV was continued in most patients for a minimum of 10 days following TBI.


Conclusions: Levetiracetam is a well-tolerated antiepileptic agent for patients requiring seizure prophylaxis post-TBI. This study did not reveal a significant amount of neuropsychiatric effects associated with LEV, however; additional research is needed to quantify the incidence of this known adverse effect with other risk factors and confounding variables.