Anticonvulsants to Treat Epilepsy and Alternatives

An expert in the management of epilepsy discusses whether the treatment received by the patient was appropriate, and considers when to switch to alternative therapies.

Trevor Resnick, MD: The choice of levetiracetam as the first drug is a perfectly reasonable choice, because levetiracetam is used for both patients who have focal seizures that may evolve into generalized seizures, and/or patients who have generalized seizures. The issue is that in this case his response to the medication was such where he had adverse effects, including dizziness, and tiredness, and behavioral problems with irritability and aggressive behavior.

Under those circumstances the medication should be changed, because you’re starting out with a new onset epilepsy, and what you don’t want to do is you don’t want to create what I call a comorbidity that makes the patient’s life worse than it was before he had his seizures.

That’s the second discussion: what are the other options? There are a number of other options, and I think there are multiple issues that come into those choices. But now what I would want to do is take a step back and say, “You have a normal healthy adolescent who presents with new onset generalized seizures and has an EEG [electroencephalogram] that shows this rapid spike-and-wave pattern.” 

Those 2 findings together are consistent with generalized epilepsy, possibly of what’s called juvenile myoclonic epilepsy. Then you could want to go back and find out whether he has any other features that would be consistent with juvenile myoclonic epilepsy. Have the parents noticed any staring episodes? Has he ever had early morning jerks that would provide further clinical information that would indicate that’s what he has? And with that being the diagnosis, then it allows you as a clinician to home in on what the various options are in terms of treatment, what your goals are in terms of treatment.

Now let’s get back and assume that he does have generalized tonic-clonic seizures, based upon the clinical story together with the EEG. He’s been treated with 1 medication, and you’re turning around to the family and you’re saying, “Look, this is not working. He’s having adverse effects. We need to change him to a different medication.” Under those circumstances, what I do is, I don’t say to the family, “Well, this is the best medication,” because if it doesn’t work, anything I do after that ends up being the second best choice.

So the discussion usually goes along the lines of, “These are the options, these are the positives and negatives in relationship to these other medications.” I think all these factors have to be brought to bear when you’re talking about a 16-year-old adolescent. Because there are certain behavioral patterns to adolescence where when you’re deciding how and when to treat them, that you have to take those factors into consideration. A 16-year-old does not want to be bothered with thinking that they have this entity that they have to deal with. They feel invincible, they don’t want to be dealing with any of these different things, and they want the treatment, or dealing with it, to impact their lives in as minimal a way as possible.

They don’t want to have adverse effects. They want to take medication as infrequently as possible; frankly they don’t want to take medication at all. So what you want to do is try to create an environment where they will be willing to take the medication on a consistent basis so that they will not have seizures when they have missed medication. The kinds of conversations that you will have with this kind of patient and their families is to discuss choices where it would be more feasible for a patient like him to take a medication that they would only have to take once a day.

Another question that comes up is, first of all, was levetiracetam the appropriate choice for this patient’s history? And I said, yes it was, but it’s also appropriate under these circumstances where the levetiracetam was causing adverse effects, that we need to make a change. And I had mentioned to you that we talk about choices, not about a specific change, and what we take into account for the choices are the patient’s lifestyle, their comorbidities, what is specific about that patient that would make you veer in the direction of choice A versus choice B?

And one of the questions that comes up often from patients, and sometimes also from other neurologists is, “Well, are the newer medications better than the older medications?” I think certainly from an adverse effect standpoint, the newer medications have advantages in that the adverse effect profile and the long-term adverse effect profile are less than the older medications. There are no data from an efficacy standpoint that the newer medications are better than the older medications. 

But if you had looked back at patients taking older medications and you spoke to them about their seizures, the discussion was always a bimodal discussion. It was seizures versus adverse effects, and it was a balance between the 2. And quality of life equally revolved around adverse effects as it did about seizure control. In many patients, if you look at quality of life reports, their report back was that the adverse effects of the medication, even though it controlled the seizures, was to some extent worse than the actual seizures themselves.

I think the issue of newer medications relates much more to cognitive adverse effects, behavioral adverse effects, than it did to the older medications. As we choose medications, a large part of the discussion, I think the major part of the discussion, is not efficacy, because the parents and the patients assume that you’re giving them a medication because you think it’s going to work. And because we don’t have data enabling us to compare efficacy, the major part of the discussion revolves around adverse effects, cognitive adverse effects, behavioral adverse effects, and long-term adverse effects. So that’s a big part of the discussion.

Another part of the discussion is the impact that taking a medication has on quality of life. If you have to take a medication 3 times a day as opposed to once a day, I haven’t had a single patient say to me, “give me the medication that I have to take 3 times a day.” It’s either once or twice a day, and those are the only 2 things that are acceptable. In certain populations, once a day becomes a primary consideration. That’s why this case is such an interesting case because it’s specifically an adolescent, and adolescents invariably think that they are invincible, and they don’t want to be dealing with any of this medication nonsense. The less of an impact on what they have to do to keep themselves healthy, the better it is for the patient.

And the reason for that is the most common reason for a patient having seizures is that they don’t take their mediation. So just being able to have their medication and take their medication on a reliable basis, you are upping the ante in terms of the likelihood of having good seizure control.

That’s a very important factor, especially in this patient. This is the kind of scenario where we have all the discussions about adverse effects and long-term adverse effects and cognitive adverse effects, and how does this fit with this patient’s lifestyle. So the discussion ends up being a multilevel discussion. It’s not just, “I’ve had a seizure, take this medication;” it’s a much broader discussion than it used to be.