Epilepsy Management: Gauging Limitations of Guidelines

Michael R. Sperling, MD: So, Kate, if the situation were somewhat different and there was a risk factor—let’s say the patient had had encephalitis or something else where you decide the probability of relapse is relatively high and you want to start someone on a drug—do the guidelines that have been published by the American Academy of Neurology, or the Epilepsy Society, or the International League Against Epilepsy influence your decision? Do you rely on those guidelines to choose drugs? And what are the advantages you see of that and what are the disadvantages?

Kathryn A. Davis, MD, MS, FAES: I think the guidelines are important to keep in mind such that we should be following them when we can. They don’t fit every patient. I think for physicians like myself who only treat epilepsy patients, at our practice, I don’t have to think about the guidelines. It’s actually how I think mostly in terms of what’s the most appropriate medication for a given patient. And, as Eric pointed out, we fortunately have many medications now that have fewer adverse effects, fewer drug interactions, and are better tolerated. And so it can help guide clinicians in terms of when to pick a medication and what medication to go to.

Michael R. Sperling, MD: What are the limitations of the guidelines, Trevor, perhaps?

Trevor J. Resnick, MD: I think guidelines are just what they are, which are guidelines. They’re not templates. Although, as Kate is saying about the majority of patients and scenarios that fit those guidelines, in a majority of cases there are patients who fall outside of the bell-shaped curve. And, for those patients, the guidelines really are not necessarily appropriate. And it’s important to keep that in mind because we have to be able to think laterally under those situations when the guidelines don’t fit. But I think if you understand what guidelines are and what guidelines are for, they’re important because they provide a framework for us to think. As Kate was saying, I think for those of us in the field, we tend to do it and then look back and say we are following the guidelines because that’s the way it is.

Michael R. Sperling, MD: Right. While I’m moderating, I can’t resist interjecting one opinion to be a slight curmudgeon perhaps in this. But I think it’s important to remember that the guidelines are a best practice, but they’re based upon clinical trials that are published that have major limitations. So my average patient who I treat in the office does not qualify for any clinical trial. The clinical trials have very specific criteria, and it’s a small proportion of my intractable patients who I can put in clinical trials. So the data from the clinical trial used to develop the guidelines already do not quite apply, strictly speaking.

Secondly, the data are generated by pharmaceutical trials met to meet FDA guidelines, and the big gap there is that the FDA doesn’t like comparative trials. They want a drug against placebo, where perhaps a drug against natural history they’re now starting to allow. In the world, we’re not comparing a drug against placebo, we’re deciding if I choose drug A, B, C, D, E, F, G, etcetera. And we don’t have good guidelines really comparing that in this population. And, again, patients with major psychiatric problems, patients with significant medical comorbidities and a variety of conditions, just aren’t covered.

So I think we have to keep in mind that the guidelines are wonderful, but, as you said, they’re not a template. And certainly if only 2 companies did studies in elderly people, for example, to assess the efficacy, well then we only have the highest level of evidence for those 2 drugs. It doesn’t mean the other drugs might not be equally good or better. That’s a limitation.