title: Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.|Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.|Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, U.S.A.|Department of Neurology, Valais Hospital, Sion, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Alvarez
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Drislane
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: M Brandon
authors.initials: MB
authors.lastname: Westover
authors.affiliation: Department of Clinical Neurosciences, CHUV and University of Lausanne, Lausanne, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Novy
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Dworetzky
authors.affiliation: Department of Clinical Neurosciences, CHUV and University of Lausanne, Lausanne, Switzerland.
authors.forename: Andrea O
authors.initials: AO
authors.lastname: Rossetti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D002998:Clonazepam / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use*; D008875:Middle Aged; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies; D013226:Status Epilepticus / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D001569:Benzodiazepines; D002998:Clonazepam; D008140:Lorazepam; D008874:Midazolam
keywords: Benzodiazepines; Coma; Critical care; Epilepsy; Neurologic emergency