Pharmacological management of epilepsy: recent advances and future prospects.

There is still a need for new antiepileptic drugs (AEDs) as the clinical efficacy, tolerability, toxicity or pharmacokinetic properties of existing AEDs may not be satisfactory. One new AED has recently been approved (rufinamide in 2007) and six others are in late-stage development (phase III and onwards) [brivaracetam, carisbamate, eslicarbazepine, lacosamide, retigabine and stiripentol]. The purpose of this review is to provide updated data on proposed mechanisms of action, efficacy and tolerability on these new AEDs, and to discuss the rationale for their development and possible advantages compared with existing treatment, based on recent publications and MEDLINE searches.Rufinamide, brivaracetam and stiripentol have been given the status of orphan drugs. Rufinamide was approved in Europe in 2007 for the use in Lennox-Gastaut syndrome. Brivaracetam has gained orphan status for development in progressive and symptomatic myoclonic seizures in Europe and the US, respectively. Stiripentol has gained orphan status in children with Dravet's syndrome and pharmaco-resistant epilepsy. All of these drugs demonstrate efficacy as adjunctive therapy in partial seizures. Three of the drugs are derivatives of existing AEDs: brivaracetam is a derivative of levetiracetam with improved affinity for the target molecule; carisbamate is a derivative of felbamate with improved tolerability; and eslicarbazepine is a derivative of carbamazepine with less interaction potential and no auto-induction. Lacosamide, retigabine, rufinamide and stiripentol are new compounds, unrelated to other AEDs.Further investigation and development of new broad-spectrum drugs is important for improved treatment of patients with epilepsy and other neurological and psychiatric disorders.