Update on novel antiepileptic drugs

Abstract

Epilepsy is the most common serious neurological condition. Approximately 20% of patients with epilepsy are resistant to current antiepileptic drugs (AEDs), and newly licensed AEDs have not significantly changed the prognosis for this group. New AEDs are thus still needed to treat this refractory group. Although established AEDs have been very successful in treating epilepsy, they are associated with frequent adverse events, and newer AEDs with better side-effect profiles may eventually replace the older drugs as first-line therapy. There has, however, been caution in using new AEDs as first-line treatment because of questions of long-term safety and cost. As well as treating epilepsy, there is a need for drugs that prevent the development of epilepsy following, for example, head injury. None of the established AEDs has been shown to achieve this, but newer drugs have been found to be anti-epileptogenic in animal models. Whether this is so in the clinical situation has yet to be established. This is a potentially large under-investigated market. Although new AEDs have largely been developed through widespread screening in animal epilepsy models and the modification of existing compounds, there has been a growth in the rational development of AEDs. Drugs that increase brain g-aminobutyric acid (GABA) concentrations have now become well-established, and a new drug, tiagabine, that operates via this mechanism is shortly to be launched in a number of countries. Research has recently been concentrated on the development of drugs whose antiepileptic effect is mediated through glutamate receptors. Initial investigation of N-methyl-D-aspartate (NMDA) receptor antagonists in patients with epilepsy was disappointing, but drugs that act via non-NMDA glutamate receptors, and metabotropic glutamate receptors look promising.