Reason for Optimism in Epilepsy?

Andrew N. Wilner, MD; Michael A. Rogawski, MD, PhD


June 29, 2012

In This Article

Editor's Note:
Following the 11th Eilat Conference on New Antiepileptic Drugs, held in Eilat, Israel, Dr. Andrew Wilner spoke with Dr. Michael Rogawski, Professor of Neurology at the University of California, Davis, about promising new directions is epilepsy therapeutics.

Antiepileptic Drug Development: Introduction

Andrew N. Wilner, MD: Dr. Rogawski, you and I just returned from the 11th Eilat Conference on New Antiepileptic Drugs, held in Eilat, Israel. Since the first Eilat Conference in 1992, 14 new antiepileptic drugs have been approved by the US Food and Drug Administration (FDA). That seems to represent a lot of progress.

Michael A. Rogawski, MD, PhD: It is true that we have made remarkable progress, and our progress has been chronicled by these meetings in Eilat, where we discuss the new drugs in the pipeline. But there is no doubt that we still have a need for better antiepileptic drugs (AEDs).

The objective of AED therapy is to achieve freedom from seizures without side effects. It is generally believed that AED resistance -- which means the failure to achieve freedom from seizures -- still occurs in 30%-40% of patients with focal epilepsies, which are the most common type of epilepsy in adults. The percentage of patients who have AED resistance may in fact be as high as 60% in patients with symptomatic focal epilepsies, which are those that include evidence of unequivocal signs of brain damage, such as mesial temporal sclerosis.

Dr. Wilner: In other words, the first lesson is that about one half of patients respond well to AED treatment. And second, distinguishing seizure types and syndromes is important for selecting an effective drug.

Dr. Rogawski: That is correct. But even when we select the most effective drugs for a patient, we still fall short of achieving freedom from seizures -- which is the goal of therapy -- in a very large percentage of our patients.

Dr. Wilner: How does the pipeline look? Are we making progress in that direction?

Dr. Rogawski: Before we talk about that, I would like to reflect on the progress that we have made so far.

You mentioned that 14 new AEDs have been approved by the FDA since 1992. The emerging evidence indicates that these new drugs have indeed made an impact on the treatment of epilepsy from an efficacy standpoint. For example, a recent study[1] found that as many as one half of all patients considered to be AED resistant are able to achieve freedom from seizures on a new AED. This requires trial and error, and often patients try 2 or more AEDs as they approach this goal.

The availability now of a large number of choices provides the opportunity to find a drug that allows an individual patient to achieve freedom from seizures. However, many experts are not convinced that the new drugs have this degree of impact from an efficacy standpoint. It is certainly controversial.

But there is no question that the new AEDs have provided many advantages for patients in terms of tolerability, safety, and pharmacokinetics. Many of the new drugs have fewer drug/drug interactions and are easier to use. Some of the newer drugs have longer half-lives, so they only need to be administered once or twice a day, making them easier for patients to take. Many of the new drugs are easier in the sense that they require less monitoring with blood tests.

And although none of the new drugs is free of side effects, they tend to have different side effects, and in some cases the side effects can be individually tailored to the patient's individual situation. For example, topiramate causes weight loss, which may be desirable in some patients but not in others.

So, even if you disagree with the view that the new drugs have been beneficial in terms of increasing the number of patients who achieve freedom from seizures, overall, I do not think there is any question that the new drugs have been helpful and have advanced therapeutics with respect to tolerability, safety, and pharmacokinetics.


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