How a new medication shows promise in targeting difficult to treat Partial Epilepsy seizures?

What is Epilepsy?

Epilepsy is a neurological condition, which affects the nervous system. Epilepsy is also known as a seizure disorder. It is usually diagnosed after a person has had at least two seizures that were not caused by some known medical condition like alcohol withdrawal or extremely low blood sugar.  Sometimes, according to the International League Against Epilepsy, epilepsy can be diagnosed after one seizure, if a person has a condition that places them at high risk for having another.

The seizures in epilepsy may be related to a brain injury or a family tendency, but most of the time the cause is unknown. The word "epilepsy" does not indicate anything about the cause of the person's seizures, what type they are, or how severe they are.

What are types of Epilepsy Seizures?

Seizures take many forms. Before your doctor can prescribe the right treatment, he or she must figure out which type (or types) you have. That's the purpose of all the tests discussed in the Diagnosis section—not just to tell whether you have epilepsy but also to tell what kind. There are so many kinds of seizures that neurologists who specialize in epilepsy are still updating their thinking about how to classify them. Usually, they classify seizures into two types, primary generalized seizures and partial seizures. The difference between these types is in how they begin:

Primary generalized seizures

Primary generalized seizures begin with a widespread electrical discharge that involves both sides of the brain at once. Hereditary factors are important in many of these seizures.

Partial seizures

Partial seizures begin with an electrical discharge in one limited area of the brain. Some are related to head injury, brain infection, stroke, or tumor, but in most cases the cause is unknown.

Why this new study is so important?

This study is particularly important primarily because it represents a new medication with a new mechanism of action. The drug reduced seizures at a minimum of 4 mg dose to 8 mg per day. The side effects that were primarily noted included dizziness but other side effects mentioned in the study included somnolence, headache, and tiredness.

This is another promising medication that works via a unique mechanism. It does bring up the possibility that combining it with another medication that works by a different mechanism could potentially be beneficial. While not addressing this specifically in the trial, it does bring up the possibility and hope for the future that this indeed may be the case. This study is also important because it helps to highlight the ever increasing number of treatment options and mechanisms by which we continue to target epilepsy. Only time will tell whether this drug will becomes a first line choice for management of patients with partial seizures.

In the July 25, 2012 Neurology articles ahead of print, Doctors French, Krauss and Biton and an international consortium of investigators presented data from a multicenter, double-blind placebo controlled trial of patients with refractory partial onset seizures who were on up to three antiseizure drugs. The patients were randomized into groups of either a placebo, 8 mg, or 12 mg dose of perampanel with a total of three hundred and eighty-eight patients being treated. Of these, three hundred and eighty-seven patients provided seizure frequency data. The change in seizure frequency before and after the drug was started was the primary measure to judge the study’s success.

The Results of this new drug

The median change in seizure reduction was 21% for placebo, 26.3% for 8 mg, and 34.5% for 12 mg of perampanel. The responder rate ( defined as the number of patients who had a 50% decrease in their seizure counts) was 26.4% for the placebo, 37.6% for 8 mg, and 36.1% for the 12 mg doses, respectively. These differences, however, were not considered to be statistically different. The most common treatment side effects included dizziness, irritability, headache, falls, and imbalance. The investigators demonstrated that once a day dosing of adjunctive perampanel at doses of 8-12 mg improve seizure control in patients with uncontrolled partial onset seizures. Doses of 8 and 12 mg are safe and tolerable.

The Importance of this is…

This study is a companion to the one recently reported here on Epilepsy.com looking at lower doses. This study further underscores that even higher doses of perampanel, which in this case means 12 mg, can be utilized with some benefit to patients when dosed on a once a day basis in people who have difficult to treat partial seizures. This is an important project because it bolsters the argument for the use of perampanel, which is the first of its type of seizure drug in terms of how it prevents seizure control by targeting what is known as AMPA receptors, which help to decrease the excitability of the nerve which causes seizures.

Clearly, it will be important to hear what happens with the approval of this agent in the United States by the FDA once it is reviewed. However, assuming that the drug is approved in the United States it will be interesting to note whether this drug is helpful and how it impacts our decisions on choosing seizure medications for people who have difficult to control epilepsy.