Levetiracetam versus phenytoin for seizure prophylaxis during and early after craniotomy for brain tumours: a phase II prospective, randomised study

J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1158-62. doi: 10.1136/jnnp-2014-308584. Epub 2014 Dec 15.


Objective: Phenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period.

Methods: Patients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15-18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events.

Results: One hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2).

Conclusions: Prophylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period.

Trial registration number: UMIN13971.


Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Brain Neoplasms / complications
  • Brain Neoplasms / surgery*
  • Cohort Studies
  • Craniotomy / adverse effects*
  • Female
  • Humans
  • Levetiracetam
  • Male
  • Middle Aged
  • Neurosurgical Procedures / adverse effects*
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use*
  • Piracetam / adverse effects
  • Piracetam / analogs & derivatives*
  • Piracetam / therapeutic use
  • Postoperative Complications / prevention & control*
  • Prospective Studies
  • Seizures / prevention & control*
  • Treatment Outcome
  • Young Adult


  • Anticonvulsants
  • Levetiracetam
  • Phenytoin
  • Piracetam