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Benzodiazepines in the Treatment of Epilepsy A Review
THOMAS R. BROWNE,
J. KIFFIN PENRY,
THOMAS R. BROWNE
Section on Epilepsy, Applied Neurologic Research Branch, Collaborative and Field Research, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Md. (U.S.A.)
Search for more papers by this authorJ. KIFFIN PENRY
Section on Epilepsy, Applied Neurologic Research Branch, Collaborative and Field Research, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Md. (U.S.A.)
Search for more papers by this authorTHOMAS R. BROWNE,
J. KIFFIN PENRY,
THOMAS R. BROWNE
Section on Epilepsy, Applied Neurologic Research Branch, Collaborative and Field Research, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Md. (U.S.A.)
Search for more papers by this authorJ. KIFFIN PENRY
Section on Epilepsy, Applied Neurologic Research Branch, Collaborative and Field Research, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Md. (U.S.A.)
Search for more papers by this authorAbstract
SUMMARY
The anticonvulsant effect of benzodiazepines is reviewed, both on experimentally produced seizures and on epilepsy in man, including aspects of clinical pharmacology and toxicology. The drugs are chlordiazepoxide (Librium®), diazepam (Valium®), oxazepam (Serax®), nitrazepam (Mogadon®) and clonazepam. Flurazepam (Dal-mane®) has not been tested extensively.
The benzodiazepines suppress generalized EEG discharges but not focal ones. They are highly effective in stopping absence (petit mal), infantile and other myoclonic seizures, akinetic, photosensitive and alcohol withdrawal attacks. They are the drugs of choice to arrest status epilepticus of all kinds and eclamptic convulsions. Grand mal, focal and partial (psychomotor, temporal lobe) seizures are less often controlled and grand mal may be aggravated.
Because tolerance may develop, the benzodiazepines are most effective when given parenterally and less effective when given continuously by mouth. Toxicity, usually drowsiness or ataxia, is less apt to be troublesome when the dose is increased gradually.
RESUME
On a revu ľeffet anticonvulsant des benzodiazepines à la fois sur les crises produites expérimentalement et sur ľépilepsie chez ľhomme, en tenant compte des aspects de pharmacologic clinique et de toxicologic Les drogues étudiées sont le chlordiazepoxide (Librium®), le diazepam (Valium®), ľoxazepam (Serax®), le nitrazepam (Mogadon®) et le clonazepam (Rivotril®). Le flurazepam (Dalmane®) n'a pas été testé de façon étendue.
Les benzodiazepines suppriment les décharges EEG généralisées mais non les décharges focales. Elles sont très efficaces pour arrêter les absences (petit mal), les crises infantiles et les autres crises myocloniques, les crises akinétiques et les crises photosensibles et les crises après sevrage alcoolique. Les benzodiazepines sont les drogues de choix pour arrêter les états de mal de toute sorte et les crises eclamptiques.
Les crises grand mal, focales et partielles (psychomotrices, temporales) sont moins bien contrôlées et le grand mal peut être aggravé.
Parce que la tolérance peut se développer, les benzodiazepines sont plus efficacies quand elles sont données par voie parenterale et moins efficaces quand elles sont donnees de façon continue per os. La toxicité, généralement somnolence ou ataxie est moins fréquente quand le traitement est augmenté progressivement.
ZUSAMMENFASSUNG
Überblick über die antikonvulsive Wirkung der Benzodiazepine auf experimentell erzeugte Krämpfe und auf die Epilepsie beim Menschen; klinisch pharmakologische und toxikologische Aspekte. Folgende Präparate werden berücksichtigt: Chlor-diazepoxyd (Librium®), Diazepam (Valium®), Oxazepam (Serax®), Nitrazepam (Mogadon®) und Clonazepam. Flurazepam (Dalmane®) wurde nicht ausführlich getestet.
Die Benzodiazepine unterdrücken generalisierte EEG Entladungen, nicht aber fokale. Ihre anfallverhütende Wirkung erstreckt sich vorwiegend auf Absencen (Petit Mai), infantile und andere myoklonische Anfälle, akinetische, photosensible Anfälle und solche bei Alkoholentzug. Es handelt sich um Präparate der ersten Wahl zur Behandlung jedes Status Epilepticus und eklamptischer Krämpfe. Die Wirkung auf Grand Mai-, fokale- und Partialanfälle (psychomotorische-, Temporallappen-anfalle) ist geringer, ein Grand Mai kann verstärkt werden.
Da sich eine Gewöhnung gegenüber den Präparaten entwickeln kann, ist die Wirkung der Benzodiazepine am größten, wenn sie parenteral gegeben werden, geringer bei oraler Applikation über einen längeren Zeitraum. Toxische Nebenwirkungen, gewöhnlich Schläfrigkeit oder Ataxie, sind weniger zu befürchten, wenn die Dosierung allmählich erhöht wird.
RESUME
El efecto anticonvulsivo de las benzodiacepinas es revisado tanto desde el punto de vista experimental como en la epilepsia del hombre, incluyendo aspectos de farma-cologia clinica toxicología. Las drogas estudiadas son clorodiacepoxido (Librium®), diacepam (Valium®), oxacepam (Serax®), nitracepam (Mogadon®) y clonacepam. El flurazepam (Dalmane®) no ha sido estudiado.
Las benzodiacepinas suprimen las descargas EEG generalizadas, pero no las focales. Son extraordinariamente eficaces en las ausencias (petit mal), en los espas-mos infantiles y otras crisis mioclonicas, y en las crisis aquinéticas fotosensibles o debidas a la supresión de alcohol. Constituyen el medicamento de electión para detener el status epiléptico y las convulsiones eclám ticas. Las crisis de gran mal, focales y parciales (psicomotoras, lóbulo temporal) son ineficazmente controladas y el gran mal puede incluso verse agravado.
Las benzodiacepinas son más activas cuando se administran por via parenteral y menos eficaces “per os” debido a que en estas condiciones su efecto puede ser tran-sitorio. La somnolencia y la ataxia constituyen los principales efectos secundarios, que pueden evitarse, mediante una administration progresiva.
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