Advances in Medication Therapies for Epilepsy by Ronald Fields, MD

For patients with intractable epilepsy, there continues to be hope for improvement as treatment options continue to expand.  Over the last four years, several new anti-seizure medications have become available in the U.S. and scientific studies continue to investigate novel treatment options for epilepsy.

Recent Anti-Seizure Medications: 
Perampanel (Fycompa) was approved in October 2012 as add-on therapy for the treatment of partial epilepsy in patients 12 years old and older. The clinical trials involved patients who had on average one seizure per week. The medication was taken over 13 weeks and the percentages of patients with a 50% responder rate (the percentage of patients in a clinical trial that decrease their seizure rate by 50% or greater) were 28.5%, 35.3%, and 35.0% for 4, 8, and 12 mg, respectively. Common side effects can include dizziness, fatigue, irritability, clumsiness, and weight gain. Interactions with other seizure medications should be monitored.

Clobazam (Onfi) was approved for use in the U.S. in October 2011 as an add-on therapy for the treatment of Lennox-Gastaut Syndrome. It is a benzodiazepine similar to Valium, Ativan, and Klonopin that has been available for the treatment of epilepsy in other countries since 1984. Many studies have been performed over the years showing improved seizure control for multiple seizure types. The 50% responder rate ranged from 38% to 85% depending on the study. The clinical trials for clobazam approval in the U.S. showed that it is effective for improving ‘drop seizures’ in patients with Lennox-Gastaut Syndrome. Common side effects can include somnolence, irritability, ataxia, and drooling.

Ezogabine (Potiga) was approved in June 2011 as add-on therapy for the treatment of partial epilepsy in adults. The clinical trials involved patients who had 8-12 seizures per month.  The clinical trials showed reduction in seizure rate of 24% to 27% depending on the dosage used. Typical dosages are 200mg to 400mg three times daily. Common side effects can include dizziness, confusion, fatigue, and somnolence. Difficulty urinating is a less common side effect but should be monitored. Interactions with other seizure medications can also occur.

Lacosamide (Vimpat) was approved in June 2009 as add-on therapy for the treatment of partial epilepsy in adults. The clinical trial for lacosamide examined patients with difficult to control epilepsy over a 12-week period. A dosage of 100mg twice daily was found to reduce the median seizure rate by 26%, and a dosage of 200mg twice daily reduced the median seizure rate by 39%. The 50% responder rate for patients receiving 100mg twice daily was 33%, and for patients receiving 200mg twice daily it was 41%. The medication was well tolerated overall with the most common side effects involving typical symptoms of being over medicated (dizziness, nausea, fatigue, clumsiness, blurry/double vision). Caution is warranted in patients with a history of heart arrhythmia or severe heart disease.

Rufinamide (Banzel) was approved in November 2008 as add-on therapy for the treatment of Lennox-Gastaut Syndrome in patients four years of age and older. The clinical trial for rufinamide examined patients with Lennox-Gastaut Syndrome having at least 90 seizures per month and they were tested over a 12-week interval. The goal dose was 45mg/kg/d in children (1600mg twice daily in adults) and this resulted in a 32% reduction in median seizure rate. Common side effects can include dizziness, fatigue, nausea, diplopia, vision blurred, headache, and balance difficulties. Drug level interactions could occur when rufinamide was combined with carbamazepine, valproate, phenobarbital, lamotrigine, primidone, and phenytoin. Rufinamide should not be used in patients with Familial Short QT Syndrome.

Research investigating new treatments for epilepsy is ongoing and extensive. The website www.epilepsy.com is a valuable resource for epilepsy patients and practitioners and also offers a section on advancements in epilepsy therapy:   http://www.epilepsy.com/etp/pipeline_new_therapies

The Epilepsy Therapy Pipeline offers webcasts from the meeting in February of this year: http://www.epilepsy.com/etp/pipeline2012_webcasts

Dr. Robert S. Fisher, M.D., Ph.D. has a good summary of developments in epilepsy therapies written in 2010, but many are still under investigation:

http://www.epilepsy.com/epilepsy/newsletter/mar10_devices

http://www.epilepsy.com/epilepsy/newsletter/apr10_medicines 

Dr. Fields is an epileptologist at the Saint Luke’s Neuroscience Institute Comprehensive Epilepsy Center in Kansas City, MO, and serves on the Epilepsy Foundation of Missouri & Kansas professional advisory board.

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