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Developments in Anti-Seizure Medications

Seizure Medications Introduced From 2007 to 2012

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Updated December 26, 2012

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Neurology is a rapidly changing field, with new developments occurring all the time. Within the field of epilepsy, eight new anti-epileptic medications have been approved by either the Food and Drug Administration (FDA) or the European Medicines Agency in the five years between 2007 and 2012.

Most of these medications are approved for partial seizures, that is seizures that just start in one spot of the brain rather than all at once. These medications have proved harder to control than generalized seizures. In addition, some of the new anti-seizure drugs are used in hard-to-treat children's epilepsies like Lennox-Gastaut syndrome.

In addition, many of these medications are beginning to be used off-label, meaning that doctors are prescribing them for things other than what the FDA has allowed the company to advertise.

Stiripentol- Stiripentol was authorized by the European Medicine Agency in 2007. The drug is not available in the United States.

The intended use of stiripentol is in young patients with Dravet's syndrome, a rare and potentially serious form of epilepsy. The exact mechanisms is unknown but it's thought to work in a similar manner to barbiturates.

Stiripentol is metabolized by the liver. Other drugs that are also metabolized by the liver, such as phenytoin may not be metabolized as quickly in someone who is also taking steripentol, meaning that concentrations of these drugs in the blood may be higher. On one hand, this may make the drug more effective, but on the other hand, levels may become so high that the drug becomes toxic. Careful monitoring is recommended if other drugs are being taken.

Lacosamide- Lacosamide was approved in 2008 as adjunctive treatment in partial-onset seizures in adults. It is increasingly found off-label for generalized seizures, including status epilepticus as well. The drug works on a sodium channel in a unique fashion from previous drugs. It also has few interactions with other drugs.

The most common side effect with lacosamide is dizziness, which occurs in about a quarter of all who take the drug. Other potential side effects include balance disorders or double vision.

Rufinamide- Rufinamide was the first antiepileptic drug to be approved for children before it was for adults. The drug is intended for treatment of seizures in children with oxcarbazepine. The drug has been approved in the European Union since 2009, and is in trials in the United States.

Vigabatrin- Vigabatrin has been available for years outside the United States, but until 2009 was not permitted in the United States due to the side effects of vision loss in up to a third of people who take the drug. It was approved in the United States in 2009, but only in severe situations, including children less than two years old with infantile spasms.

Ezogabine- Ezogabine, called ritigabine in Europe, is the first anti-epileptic medication to target a potassium channel. It was approved in 2011 for treatment of partial seizures. Unfortunately, it can have a side effect of urinary retention.

Side effects of this medication can include somnolence, dizziness and confusion.

Clobazam- Clobazam is a benzodiazepine, but is slightly different in structure. The drug has been available outside the US since 1970, but was only approved by the FDA in 2011 as an adjunctve treatment in children with Lennox-Gastaut syndrome, and resulted in up to a 70 percent reuction in seizures in these patients. The drug is further being used in other epilepsy syndromes, as well as many different kinds of seizures. As is often the case with anti-epileptic medications, those with kidney or liver damage are at increased risk of side effects from this medication.

Perampanel- Like other new anti-epileptics, perampanel has a new mechanism of action, targeting the α-amino-3-hydroxy-5-methyl-4-isozazole proprionic acid (AMPA) ionotropic glutamate receptor. Perampanel may interact with drugs like carbamazepine, oxcarbazepine or phenytoin. At this point there is little clinical experience on with this drug, as it was only approved in October of 2012.

At present, almost a third of patients with epilepsy have seizures that cannot be well-controlled with medication alone. By bringing forth new drugs with new strategies, our hope is to one day have a world that is seizure free.

Sources:

Bialer M, White HS. Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 2010;9:68-82.

Faught RE. Efficacy and Adverse Effects of Newer AEDs in Approved Indications. In: American Epilepsy Society Annual Meeting; 2012; San Diego, California, 2012.

Johannessen Landmark C, Johannessen SI, Tomson T. Host factors affecting antiepileptic drug delivery-pharmacokinetic variability. Adv Drug Deliv Rev 2012;64:896-910

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