A Comparison of Seizure Prophylaxis: Phenytoin Versus Levetiracetam

Abstract

Phenytoin and levetiracetam are both antiepileptic drugs (AEDs) used for seizure prophylaxis. However, to date, there is a paucity of literature comparing their relative efficacies. In this narrative review, we seek to determine if there is greater advantage between the two AEDs, levetiracetam and phenytoin. Phenytoin is the more traditional AED of the two as it has been medically used for a much longer time than levetiracetam. However, levetiracetam, the newer AED of the two, has fewer side effects than phenytoin and fewer drug-drug interactions. Although past studies have aimed to compare the efficacy of phenytoin versus levetiracetam, there is no clear consensus as to if there is a clinical advantage to one over the other. Here, we have analyzed several studies published between 2013 and 2020 in the hopes of having a better understanding of which AED is more efficient in preventing seizures. Many factors can contribute to determining which AED is the better fit for patients, including pricing, risk for adverse drug effects, and level of patient monitoring. After analysis of past research, the more advantageous AED still remains unclear. Future research must be conducted that involve large patient populations, stratifying age populations, and studies analyzing cost-effectiveness to clearly determine if there is indeed a more advantageous AED between levetiracetam and phenytoin.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

“…Use of newer-generation antiseizure medications that may be more effective or less toxic than phenytoin remains a topic of discussion. 424 A single-blinded randomized study of levetiracetam versus phenytoin demonstrated the same outcomes with respect to mortality or seizure control as evaluated by cEEG. Therapy with levetiracetam resulted in a lower incidence of adverse effects as evaluated by the Glasgow Outcome Scale–Extended and Disability Rating Scale.…”

Seizure Prophylaxis in Young Patients Following Traumatic Brain Injury

“…[ 18 ] Levetiracetam is another antiepileptic drug that exhibits a new appealing alternative, considering no need for monitoring, predicted metabolism, nonprotein binding, and minimal adverse events profile. [ 11 ] Some studies have compared the safety and efficacy of phenytoin with levetiracetam. An earlier meta-analysis by Yang et al .…”

“…Moreover, it has an unpredictable pharmacokinetic profile and a narrow therapeutic index, which requires monitoring of levels in critically ill patients. [ 11 ] However, the current literature on its role as anti-seizure prophylaxis remains controversial. Levetiracetam has been more widely used as ASM due to its tolerable safety profile, less sedation effect, and similar effectiveness to phenytoin in preventing EOS.…”

Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the “Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial” (ADAPT) Dataset, 2014–2017*

“…The most common anticonvulsants used to prevent seizures after severe TBI are phenytoin and levetiracetam (7,8). Levetiracetam is a newer antiepileptic drug with fewer reported side effects, fewer drug interactions, and a simpler dosing regimen than phenytoin (7,8).…”