Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison

Epilepsia. 2015 Aug;56(8):1275-85. doi: 10.1111/epi.13056. Epub 2015 Jul 3.


Objective: Benzodiazepines (BZD) are recommended as first-line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date.

Methods: We identified all patients treated with CLZ, LZP, or MDZ as a first-line agent from a prospectively collected observational cohort of adult patients treated for SE in four tertiary care centers. Relative efficacies of CLZ, LZP, and MDZ were compared by assessing the risk of developing refractory SE and the number of antiseizure drugs (ASDs) required to control SE.

Results: Among 177 patients, 72 patients (40.62%) received CLZ, 82 patients (46.33%) LZP, and 23 (12.99%) MDZ; groups were similar in demographics and SE characteristics. Loading dose was considered insufficient in the majority of cases for LZP, with a similar rate (84%, 95%, and 87.5%) in the centers involved, and CLZ was used as recommended in 52% of patients. After adjustment for relevant variables, LZP was associated with an increased risk of refractoriness as compared to CLZ (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.66-15.5) and with an increased number of ASDs needed for SE control (OR 4.35, 95% CI 1.8-10.49).

Significance: CLZ seems to be an effective alternative to LZP and MDZ. LZP is frequently underdosed in this setting. These findings are highly relevant, since they may impact daily practice.

Keywords: Benzodiazepines; Coma; Critical care; Epilepsy; Neurologic emergency.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / therapeutic use*
  • Benzodiazepines / therapeutic use*
  • Clonazepam / therapeutic use*
  • Cohort Studies
  • Female
  • Humans
  • Lorazepam / therapeutic use*
  • Male
  • Midazolam / therapeutic use*
  • Middle Aged
  • Practice Patterns, Physicians'*
  • Prospective Studies
  • Status Epilepticus / drug therapy*
  • Treatment Outcome


  • Anticonvulsants
  • Benzodiazepines
  • Clonazepam
  • Lorazepam
  • Midazolam