Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam

Epilepsia. 2011 Jul;52(7):1292-6. doi: 10.1111/j.1528-1167.2011.03056.x. Epub 2011 Apr 11.


Purpose: Phenytoin (PHT), valproic acid (VPA), or levetiracetam (LEV) are commonly used as second-line treatment of status epilepticus (SE), but comparative studies are not available.

Methods: Among 279 adult SE episodes identified prospectively in our tertiary care hospital over 4 years, we retrospectively identified 187 episodes in which PHT, VPA, or LEV were given after benzodiazepines. Patients with postanoxic SE were not included. Demographics, clinical SE features, failure of second-line treatment to control SE, new handicap, and mortality at hospital discharge were assessed. Uni- and multivariable statistical analyses were applied to compare the three agents.

Key findings: Each compound was used in about one third of SE episodes. VPA failed to control SE in 25.4%, PHT in 41.4%, and LEV in 48.3% of episodes in which these were prescribed. A deadly etiology was more frequent in the VPA group, whereas SE episodes tended to be more severe in the PHT group. After adjustment for these known SE outcome predictors, LEV failed more often than VPA [odds ratio (OR) 2.69; 95% confidence interval (CI) 1.19-6.08]; 16.8% (95% CI: 6.0-31.4%) of second-line treatment failures could be attributed to LEV. PHT was not statistically different from the other two compounds. Second-line treatment did not seem to influence new handicap and mortality, whereas etiology and the SE Severity Score (STESS) were robust independent predictors.

Significance: Even without significant differences on outcome at discharge, LEV seems less efficient than VPA to control SE after benzodiazepines. A prospective comparative trial is needed to address this potentially concerning finding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Anticonvulsants / therapeutic use*
  • Chi-Square Distribution
  • Female
  • Humans
  • Levetiracetam
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenytoin / therapeutic use*
  • Piracetam / analogs & derivatives*
  • Piracetam / therapeutic use
  • Retrospective Studies
  • Status Epilepticus / drug therapy*
  • Treatment Failure
  • Valproic Acid / therapeutic use*


  • Anticonvulsants
  • Levetiracetam
  • Valproic Acid
  • Phenytoin
  • Piracetam