Background: Levetiracetam is a soluble ethyl analogue of the nootropic agent piracetam that is utilized primarily for epilepsy treatment. Studies have shown levetiracetam has preferred pharmacokinetic and pharmacodynamic properties compared to phenytoin, however, limited data exist regarding neuropsychiatric side effects. Purpose: To evaluate the incidence of neuropsychiatric events in patients under the age of 75 and over the age 75 years receiving levetiracetam for seizure prophylaxis following traumatic brain injury (TBI). Methods: This study was a retrospective cohort analysis conducted at the University of Toledo Medical Center (UTMC) between January 1, 2023, and March 15, 2025. Inclusion criteria required adults aged >18 years old 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. For the primary endpoint, two patients (3.6%) experienced a neuropsychiatric event. There were 14 patients (25.5%) with a history of psychiatric disorders, and just 1 of those patients experienced a neuropsychiatric event while receiving levetiracetam. Conclusions: Levetiracetam is a well-tolerated antiepileptic agent for patients requiring seizure prophylaxis post TBI and did not demonstrate a significant incidence of neuropsychiatric events in this evaluation.
Centers for Disease Control and Prevention. National center for health statistics: mortality data on CDC WONDER. Accessed March 7, 2026. https://wonder.cdc.gov/mcd.html
2.
HailuBYBerheDFGudinaEKGideyKGetachewM.Drug related problems in admitted geriatric patients: the impact of clinical pharmacist interventions. BMC Geriatr. 2020;20(1):13.
3.
Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. XIII. Antiseizure prophylaxis. J Neurotrauma. 2007;24 suppl 1:S83-S86.
4.
RobbinsBAlmassalkhiLBaumR, et al. Pharmacotherapy adjuncts for traumatic brain injury: a narrative review of evidence and considerations in the emergency department. Am J Emerg Med. 2025;89:78-84.
5.
PatanwalaAEKuritaATruongE.Low-dose levetiracetam for seizure prophylaxis after traumatic brain injury. Brain Inj. 2016;30(2):156-158.
6.
OhmanKKramBSchultheisJ, et al. Evaluation of levetiracetam dosing strategies for seizure prophylaxis following traumatic brain injury. Neurocrit Care. 2023;38(2):345-355.
7.
KwonSJBarlettaJFHallST, et al. Lacosamide versus phenytoin for the prevention of early post traumatic seizures. J Crit Care. 2019;50:50-53.
8.
WrightCDowningJMungallD, et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol. 2013;4:192.
9.
HasegawaNFukudaM.The effect of lacosamide on psychiatric comorbidities in patients with epilepsy. Epilepsy Behav Rep. 2020;14:100402.
10.
ZhangJFPiryaniRSwayampakulaAKFarooqO.Levetiracetam-induced aggression and acute behavioral changes: a case report and literature review. Clin Case Rep. 2022;10(3):e05586.
11.
2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American geriatrics society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults: 2019 AGS Beers Criteria® update expert panel. J Am Geriatr Soc. 2019;67(4):674-694.
12.
AlzuetaNOrtegaAAldazA.Influence of sex, age, and weight on levetiracetam pharmacokinetics. Ther Drug Monit. 2018;40(5):628-634.
13.
PeaseMMittalAMerkajS, et al. Early seizure prophylaxis in mild and moderate traumatic brain injury: a systematic review and meta-analysis. JAMA Neurol. 2024;81(5):507-514.
