Antiepileptic drug therapy the story so far

• Published in: Seizure (London, England) Vol. 19; no. 10; pp. 650 - 655
• Main Author: Brodie, Martin J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2010
• Subjects: Animals; Anticonvulsants - history; Anticonvulsants - pharmacology; Antiepileptic drugs; Epilepsy; Epilepsy - drug therapy; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Mechanism of action; Neurology; Pharmacoresistance; Prognosis; Pharmacoresistance; Prognosis; Mechanism of action; Antiepileptic drugs; Epilepsy
• ISSN: 1059-1311; 1532-2688
• DOI: 10.1016/j.seizure.2010.10.027

Abstract The story began on 11th May 1857 when Charles Locock commented in the Lancet on his use of potassium bromide in 15 cases of “hysterical” epilepsy in young women. The next development was the serendipitous discovery of the anticonvulsant properties of phenobarbital by Alfred Hauptmann in 1912. This predated by more than 20 years the screening of potential therapeutic agents against “electrical seizures” in cats by Houston Merritt and Tracy Putnam. The result was the launching of phenytoin in 1938. Next came primidone, ethosuximide, carbamazepine and valproic acid, all of which can be regarded as first generation antiepileptic drugs (AEDs). Shortly after their synthesis, the benzodiazepines were rapidly recognised as having anticonvulsant activity. The modern era focused on the systematic screening of many thousands of compounds against rodent seizure models under the Anticonvulsant Drug Development Program in the US. This resulted in the global licensing, in chronological order, of vigabatrin, zonisamide, oxcarbazepine, lamotrigine, felbamate, gabapentin, topiramate, tiagabine, levetiracetam, pregabalin and lacosamide. Rufinamide is available in the US and Europe for Lennox-Gastaut syndrome and stiripentol has been made available for Dravet syndrome under the European orphan drug scheme. Eslicarbazepine can be prescribed in Europe for partial seizures, but not in the US. Has all this activity improved the lives of people with epilepsy? The short answer is—probably yes, but not by very much! This paper will conclude with a précis of the views of a selected group of paediatric and adult epileptologists on the advances in pharmacological management achieved over the last 20 years.