Overview
Modern treatment of seizures started in 1850 with the introduction of bromides, which was based on the theory that epilepsy was caused by an excessive sex drive. In 1910, phenobarbital (PHB), which then was used to induce sleep, was found to have antiseizure activity and became the drug of choice for many years. A number of medications similar to PHB were developed, including primidone.
In 1938, Houston Merrit and Tracy Putnam described animal models for screening multiple compounds for antiepileptic activity in the Journal of the American Medical Association. In 1940, phenytoin (PHT) was found to be an effective drug for the treatment of epilepsy, and since then it has become a major first-line antiepileptic drug (AED) in the treatment of partial and secondarily generalized seizures.
In 1968, carbamazepine (CBZ) was approved, initially for the treatment of trigeminal neuralgia; later, in 1974, it was approved for partial seizures. Ethosuximide has been used since 1958 as a first-choice drug for the treatment of absence seizures without generalized tonic-clonic seizures. Valproate (VPA) was licensed in Europe in 1960 and in the United States in 1978, and now is widely available throughout the world. It became the drug of choice in primary generalized epilepsies and in the mid 1990s was approved for treatment of partial seizures.
These anticonvulsants were the mainstays of seizure treatment until the 1990s, when newer AEDs with good efficacy, fewer toxic effects, better tolerability, and no need for blood level monitoring were developed. A study of live-born infants in Denmark found that exposure to the newer-generation AEDs lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam in the first trimester was not associated with an increased risk in major birth defects.
The new AEDs have been approved in the United States as add-on therapy only, with the exception of topiramate and oxcarbazepine (OXC); lamotrigine (LTG) is approved for conversion to monotherapy. A meta-analysis of 70 randomized clinical trials confirms the clinical impression that efficacy does not significantly differ among AEDs used for refractory partial epilepsy.
Antiepileptic drugs should be used carefully, with consideration of medication interactions and potential side effects. This is particularly important for special populations, such as patients with HIV/AIDS.
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