Monotherapy Failure and New AEDs on the Horizon

December 9, 2008
Keli Rising

This symposium focused on monotherapy, polytherapy, and new AEDs on the horizon. The presenters explained that although monotherapy fails in approximately 50% of patients with seizure disorders or epilepsy, there are other alternatives.

It turns out that monotherapy is effective in approximately 50% of patients with epilepsy when delivered in modest doses. According to research by Kathryn Hollad, MD, PhD, the reason people fail is due to side effects and lack of efficacy. This was of particular interest to me since I am part of the 50% when monotherapy is effective in controlling seizures.

During the presentation given by Tracy Glauser, MD, he discussed what needs to happen when monotherapy fails—neurologists should consider polytherapy. There are many patients with epilepsy and seizure disorders who take multiple AEDs. He explained that the goal is to find combinations that improve efficacy and effectiveness and decrease toxicity and adverse events. One thing that neurologists need to remain aware of is the issue of drug—drug interactions. Glauser said that adverse drug reactions lead to approximately 100,000 deaths each year and two million serious reactions—these are based on global numbers and not specific to epilepsy and other seizure disorders. In a recent ADR report, of the 27 most dangerous drugs out there, two AEDs are on it, which may make patients who keep up-to-date on what’s going on in epilepsy research concerned that maybe the AED treatment they are taking will end up on the list, too. I’ll admit that these thoughts entered into my mind while listening to the presentation. Glauser recommended that in order to decrease adverse drug reactions, neurologists should consider using computer software when making treatment decisions.

One thing of particular interest was the presentation on new AEDs on the horizon given by Meir Bialer, PhD, MBA. According to Bialer, only 30% of epilepsy patients are not seizure free. What makes this especially difficult is that only 10% of AED treatments that reach the IND stage are approved. Bialer explained that one way to alleviate industry concerns is by creating second-generation drugs. On the list of 19 recently approved drugs in Bialer’s presentation, the majority of them were second-generation. One of the main reasons why this occurred is because it’s much faster to get second-generation approved versus brand new drugs. This really hit home for me because there could be some very promising research and development of treatments that might not make it to approval. It’s unfortunate that this sort of thing happens when any drug is being developed. The main message of this symposium was “no seizures, no side effects."