Addressing Nonadherence to Therapy

A key opinion leader discusses how to address nonadherence issues with patients receiving medication for epilepsy, especially adolescents.

Trevor Resnick, MD: How do you address medication adherence issues with patients? I’m a pediatric epileptologist, so addressing adherence in the younger patients is addressing adherence with the parents, not with the patient. It becomes adherence with the patient when they become an adolescent. And we already had the discussion about the fact that nonadherence is a major factor for seizures. And the biggest discussion that I have with my patients is the issue of driving.

It is a wonderful way to encourage patients to be adherent, because every kid wants to get a driver’s license. And you can only get a driver’s license if you’ve been seizure free for a period of time. That is probably the biggest positive angle that you can use to encourage patients to take their medication.

You can talk about other things, such as injuring yourself, you can die if you have a seizure, you can break a leg, terrible things can happen to you when you have a seizure. Adolescents don’t think about that. But not getting a driver’s license, that’s what they think about. That’s a big issue in terms of encouraging them to take their medication. It’s the parents who are much more concerned about the other things, but they’re not the ones who have to take the medication, it’s the adolescent who does.

One of the other reasons that I hear quite frequently from patients in terms of nonadherence relates to frequently if a patient’s seizures are relatively well controlled, they tend to deny or not report adverse events from the medication because they’re scared. They’re scared that if you make changes they’ll start having seizures again. And so what happens is they don’t report it, they have symptoms in relationship to taking medication, and they don’t like it. Then invariably what happens along the way, they’ll miss their medication, they won’t take it. They won’t take it because they don’t like the way it makes them feel. That’s a big contributor to nonadherence.

I think an important point there is that a lot of the newer medications, and newer technologies in terms of medications, are such that, number 1, some of the newer medications have long half-lives, and because they have long half-lives they only have to be given once a day. By virtue of that, you don’t need to give it twice. And if you give it late in the evening, any kind of adverse effects that may occur from a peak level happen when the patient is asleep. That’s a real advantage. And any of the newer medications with long half-lives have that as an advantage. In addition to that, because the half-lives for those patients are prolonged, it means that if they do miss a dose, the level doesn’t drop as dramatically under those circumstances, and because of that they are less likely to have a seizure due to low plasma levels. That’s one scenario, and a very important scenario.

The other scenario is that in patients who are on what I would call immediate-release medication, the way immediate-release medication is, you get a high peak level and then it drops to a trough level, and they tend to get their adverse effects when the drug is at a peak level.

Now with some of the different formulations the drug can be modified into an XR [extended-release] formulation, or a long-acting formulation, which changes that curve. So instead of having a high peak and a low trough, you have a much flatter curve, and because you have a flat curve, the adverse effects that are related to plasma levels are markedly diminished. 

So you achieve 2 things. One, you’re only getting your medication once a day. And number 2, that you’re obviating many of the adverse effects by having a flatter curve. It relates to half-life, and it relates to a formulation that allows you to only give the medication once a day. I would put that to some extent under newer medications. Even if it’s an old medication, the fact that it’s been modified in that way to make it more user-friendly with fewer adverse effects, makes it a much more attractive alternative for a patient.

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