Optimization of the treatment of epilepsy and the need to individualize the approach

Epilepsy has long been a difficult disease to treat. A large proportion of patients suffer from refractory disease and there is great heterogeneity in the disease itself, which can make the treatment selection process particularly challenging for specialists and their patients.

Although many advances have been made in the development of antiepileptic drugs for this population, epileptologists such as Jacqueline A. French, MD, Professor, Department of Neurology, NYU Langone Health Center, and Co-Director, Epilepsy Clinical Trials, NYU Langone, Comprehensive Epilepsy Center, still have concerns. The tolerability of effective therapies can vary from patient to patient, and with a lack of epilepsy specialists, these difficult-to-manage patients can often be left to the care of general neurologists who may not be expert in understanding granular of available therapeutics.

At the 2022 Annual Meeting of the American Academy of Neurology (AAN), April 2-7, in Seattle, Washington, French sat down with NeurologyLive® to discuss this challenge. She offered her perspective on the factors that influenced this difficulty and how conversations with patients and understanding their individuality can help facilitate the treatment selection process.

NeurologyLive®: Is there anything that you think needs more attention, or perhaps isn’t talked about enough, in terms of what needs to be addressed in the next few years?

Jacqueline A. French, MD: Well, one thing for me is that general neurologists are becoming more and more concerned about the complexity of selecting drugs for the right person – selecting based on the right syndrome or even the right gene – is getting very, very complex. Expecting a general neurologist to identify and use all these different drugs is going to be problematic for the next decade. We find that when an epileptologist gets hold of the patient, sometimes there are obvious solutions to that person’s problem, and other times there aren’t. But, probably, 10-15% of people can be free from seizures just by this additional knowledge of pharmacology and different drugs and their action etc. But there are not enough epileptologists to treat everyone.

We have an initiative, I co-chair a Lancet commission right now, and the purpose of the commission is to actually create a volume of The Lancet, which will be to treat epilepsy for the GP and for the GP neurologist to say, “This is how you look at patients.” As I said, when you’re choosing a drug, the next drug for a patient, you have to understand the patient’s syndrome, then you have to understand the drug, then you have to understand the patient’s comorbidities. Are they suffering from depression? Are they of childbearing age? Do they have a history of kidney stones? There are many things. We’re trying, at least, to simplify this so that people can easily look and say, “OK, my patient has A, B, and E of these 15 different comorbidities,” and look at a chart and say, “OK, I have excluded this, this and this drug, and they have this syndrome, so there are these drugs that may be available. You subtract those 3s and you’re left with that 1, a kind of menu.

Is there anything that makes progress in optimizing epilepsy treatment difficult?

In many areas—I won’t say in all areas. People have always asked me that, when they’re not in the epilepsy field, they say, “What’s the first-choice drug?” What is the second choice drug? What is the third choice drug? Whereas in many fields there is a drug that you start with, then when that fails, you switch to that drug. And when that fails, you go to that drug. It’s much simpler. In epilepsy, I can have 5 people with focal epilepsy, which is the most common epilepsy, standing in front of me and I would choose a different drug for each of them as the first drug with the highest probability of success. It’s much more complicated. It’s personalized medicine without genes, isn’t it? It is the understanding of the other characteristics of this individual that counts to make the best choice. And that could include things like, is this person able to take a medication two or three times a day, or will they only be able to take it once a day? Again, considering childbearing age and other comorbidities helps you choose the right medication for the right person. There’s so much to choose from, so I think it’s complicated – more complicated than a lot of other areas – and the stakes are high because it’s important to make sure someone doesn’t convulse. But making sure someone doesn’t convulse with a drug that doesn’t dramatically affect their ability to live their life is just as important.

How do you balance that? Is it a difficult conversation with the patient to determine this?

Well, the first thing I want to say is that as I learn in my life and my career, I kind of asked the question: do randomized controlled trials help you in the process of selecting the right medication for an individual? I put it this way, if I want to go from New York to Washington, a clinical trial is kind of like saying, “Can a bus take me from New York to Washington?” Sure, a bus could take me from New York to Washington, and that’s better than no bus, which is like comparing it to a placebo. It can tell you how many times the bus has crashed and how comfortable the bus is for everyone. But the question I want to know as a clinician and you as a patient want to know is not whether a bus can take me from New York to Washington, it’s how do I get from New York in Washington, right? A random try between things is like saying, “OK, we’ll take everyone and randomly distribute them to take the bus or the train.” Well, how did they all do it? But what if I don’t want to pay for a bus, or there’s a delay, or I feel claustrophobic, or I want to get there faster, or I knew I didn’t live anymore near train station than bus station? It may, in fact, be that one is clearly better for me than the other, but I’m going to be randomized, so you’ll never understand that. It is therefore very difficult to find the methodological and rigorous way of saying what is the ideal treatment for this person? What is the best treatment for everyone, without identifying any characteristics of these people?

The other way of saying it is kind of like saying, let’s say there was a drug that made you fat and another that made you thin, and otherwise they were exactly the same. If you randomly divide people into the drug that made you fat or the drug that made you slim, you’d say, “Well, people were equally happy with one or the other, there’s no so no difference between the two. But if you had put people who wanted to lose weight on the drug that made you thinner, and people who wanted to gain a few pounds on the drug that made you fatter, then more people would have been happy in both groups.

Is it basically just asking those kinds of questions and having that conversation with the patient?

It’s about understanding the characteristics of the drug and the important characteristics of the patient, and then matching them. It takes time, it takes thought, and you don’t always get it right the first time, of course. It may take a few tries. But the most difficult decision, honestly, for an epileptologist is when a person has had life-threatening seizures and you put them on whatever medication you think is ideal for them in any way, and the seizures stop, but she is not satisfied with this treatment. for one reason or another. Is it in their best interests to switch to another drug that they might be just as unhappy with and that might not control their seizures? Or do we tell them, “Maybe this is as good as it gets.” It’s a tough decision. But again, as an epileptologist, I shouldn’t make that decision. The person has to make that decision. They need to understand the potential risks and potential benefits of switching from one drug to another and, to the best of my ability to manage the disease, the likelihood that it will actually benefit them.

Transcript edited for clarity.

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