Trevor Resnick, MD: The breakthrough seizures are a huge issue, and actually the most common cause of breakthrough seizures is [nonadherence]. So patients take their medication, they miss a few doses, and then they have breakthrough seizures. Breakthrough seizures also could be because we don’t control the seizures well enough even if they are taking their medication. Nevertheless, the commonest cause would be [nonadherence]. So if you look at breakthrough seizures as [they relate] to the effect on the health care system and the patient, obviously that’s a significant issue. It applies much more to those patients who have generalized seizures because that generally is more likely to result in a hospitalization or a visit to the emergency [department]. And obviously, the cost of that to the health care system ends up being significant because it’s cumulative. And the cost to the patient is also financial, but more importantly, every time there’s a breakthrough seizure, it’s a huge setback for the patient. It’s a setback, No 1, in terms of the expectation that it could happen again. No 2, it has an effect especially in terms of work and home, and the psychological impact of the expectation and the fear that another seizure can occur.
R. Edward Faught, MD: Emergency [department] visits, and especially hospitalizations, are extremely expensive. You know 1 of those a year will far override the cost of a prescription. So the cost of medication is a very minor factor in treating epilepsy. In addition to [the] cost of the health care system, [it] is very disruptive to patients when they have 1 of those seizures. Often, they can have injuries, [and] they’re often out of work for several days. It’s an extremely bad thing to have. And I have to say, I don’t much like the term breakthrough seizures. That implies that [the reason they occur is] somehow magic or mysterious, but they always occur for a reason. Either the patient didn’t take their medication or they got recurrent illness, or the medication is just not working. So it’s not out of the blue. We always think there’s got to be a cause.
Trevor Resnick, MD: Patients tend to be [nonadherent] for a number of reasons. One of the common reasons that they’re [nonadherent] is [adverse] effects. They don’t want to take the medication because the medication has [adverse] effects. And because they don’t take their medication on a consistent basis, they’re more likely to have seizures. So the use of medications that have better tolerability does improve [adherence], but another thing that’s important for [adherence] is the drug half-life. If you have a medication that has a long half-life, if they do miss 1 dose and then they take the medication again, the effect of missing the dose is going to be much less. That’s actually 1 of the advantages of perampanel, which [has] a long half-life. So even if they do miss 1 dose, as long as they…go back to taking the medication again, it is somewhat protective. [For] the medications that have a shorter [half-life], missing 1 dose can have a much greater and much more significant effect and increase the risk of breakthrough seizures.
R. Edward Faught, MD: So studies have shown that only about three-quarters of patients with epilepsy take at least 80% of their medication, which is another way of saying, you know, about a quarter of people don’t really get the full prescribed dose. And it depends on a lot of factors. One of the factors is convenience. If you have to take a medication 3 or 4 times a day, it’s very difficult to get all those doses in, and everybody knows who’s tried to do that. Even for an antibiotic for 10 days, but certainly for something you have to take for years. So once-a-day medication is ideal. These medications are not too bad in that regard. The perampanel is a once-a-day nighttime medication. Lacosamide is twice a day, which usually works pretty well. But once a day, other things being equal, is superior.