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A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus

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Treiman, David M., Meyers, Patti D., Walton, Nancy Y., Collins, Joseph F., Colling, Cindy, Rowan, A. James, Handforth, Adrian, Faught, Edward +9 more·1998·New England Journal of Medicine
DOI 10.1056/nejm199809173391202
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Abstract

BACKGROUND AND METHODS: Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. RESULTS: Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days. CONCLUSIONS: As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.

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  • Benzodiazepines remain important in epilepsy management and are first-choice drugs for status epilepticus and seizures after anoxic injury.

    “Benzodiazepines (BZDs) remain important agents in the management of epilepsy.They are drugs of first choice for status epilepticus and seizures associated with post-anoxic insult”

    From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [79]

  • Results from four comparative studies suggest that lorazepam is superior to phenytoin and as effective as clonazepam, diazepam, or diazepam plus phenytoin in the initial treatment of status epilepticus.

    “Results from four comparative studies (three of blinded design) have suggested that lorazepam is superior to phenytoin and as effective as clonazepam, diazepam or the combination of diazepam and phenytoin in the initial treatment of status epilepticus (77,79,80,96).”

    From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [79]

  • Several randomized controlled trials support benzodiazepines, particularly diazepam and lorazepam, as initial therapy for status epilepticus.

    “Several randomized controlled trials support the use of BZDs (particularly diazepam and loraze- Missed dose Replaced dose Missed doses Replaced doses 0 100 200 1.0 0.8 0.6 0.4 0.2 0.0 300 Time (h) Predicted DMD concentration (µg/ml) 400 500 50 150 250 350 450 Figure 4. Simulated plasma N-desmethyldiazepam (DMD) concentration over time for immediate-release clorazepate (solid line, 7.5 mg given”

    From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [79]

  • Four randomized controlled trials support diazepam as a first-choice drug for managing status epilepticus.

    “Four randomized controlled trials support diazepam as a drug of first choice for managing status epilepticus (77)(78)(79)(80).”

    From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [79]

  • In the Veterans Affairs cooperative study, lorazepam terminated seizures in 64.9% of patients and was significantly more effective than phenytoin (P = 0.002).

    “In the Veterans Affairs cooperative study of status epilepticus, lorazepam terminated seizures in 64.9% of patients and was significantly more effective than phenytoin (P = 0.002) (79).”

    From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [79]

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Research works printed but not linked: 2

  1. Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status epilepticus: mechanisms of brain damage and treatment. Vol. 34 of Ad- vances in neurology. New York: Raven Press, 1983:441-6.
  2. DeOliverira RSP. Treatment of convulsive seizures with a new benzo- diazepine, lorazepam. Rev Bras Clin Ter 1978;7:295-8.

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Authors
Treiman, D. M., Meyers, P. D., Walton, N. Y., Collins, J. F., Colling, C., Rowan, A. J., Handforth, A., Faught, E., Calabrese, V. P., Uthman, B. M., Ramsay, R. E., Mamdani, M. B., Yagnik, P., Jones, J. C., Barry, E., Boggs, J. G., & Kanner, A. M.
Affiliations
  • University of California, Los Angeles (US)
  • New Mexico VA Health Care System (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • University of Alabama at Birmingham (US)
  • Virginia Commonwealth University Medical Center (US)
  • University of Florida (US)
  • University of Miami (US)
  • Loyola University Chicago (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1998-09-17
Volume
339
Issue
12
Pages
792-798
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199809173391202
OpenAlex
W2036467957
Cited by
1,325
References
33
Citations by year
2026: 13 · 2025: 19 · 2024: 36 · 2023: 31 · 2022: 31 · 2021: 39 · 2020: 49 · 2019: 53 · 2018: 46 · 2017: 78 · 2016: 57 · 2015: 78 · 2014: 61 · 2013: 67 · 2012: 76
FWCI
20.66
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion)
Funders
U.S. Department of Veterans Affairs
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
Keywords
generalized convulsive status epilepticus, lorazepam, diazepam, phenytoin, phenobarbital, seizure control, treatment efficacy comparison, adverse effects, seizure recurrence, coma, benzodiazepines, barbiturates
MeSH terms
Aged, Anticonvulsants, Diazepam, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Injections, Intravenous, Lorazepam, Male, Middle Aged, Phenobarbital, Phenytoin, Status Epilepticus, Treatment Outcome

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