Role of Stiripentol in Managing Dravet Syndrome


Joseph E. Sullivan, MD, and Kelly Knupp, MD, evaluate the use of stiripentol in clinical practice for the management of Dravet syndrome and Mary Anne Meskis discusses the honeymoon effect of drugs.

Joseph E. Sullivan, MD: Let’s round out just for the third drug that has FDA approval, you had mentioned stiripentol having a nice role in terms of preventing or minimizing status epilepticus, that's definitely been my experience as well. I just find it uncanny that this was the first trial done in 2000, I believe it was 2000 or at least when it was published. Small group of patients, 20 patients in each arm, and from a clinical trial design perspective, it shows the value if you can have a more homogeneous patient population if you have a desired treatment effect, that you can show superiority over placebo in a smaller group of patients. I'm wondering, aside from the status, reducing status, has your experience with stiripentol paralleled what was shown in that initial 2000 trial?

Kelly Knupp, MD: We've seen significant seizure reduction, particularly generalized tonic-clonic seizures which was the outcome measure in that study. They didn't assess the other seizure types and that it's hard to compare because we see so many different seizure types in children and adults with dravet syndrome. But I do think it has been a powerful medication. One of the things that early on when we were using the medication, I would emphasize to families that while I hope for your child to be seizure-free, our goal isn't to be seizure-freedom, our goal is to keep you out of the ICU [intensive care unit] and out of the emergency room. And that was a very reasonable goal for families, then if they say anything more, than just not having to go to the ICU and ED, they were pleased with the medication. And overall, most of our families tell us it's a very well-tolerated medication. One of the things we haven't talked much about here today is polypharmacy, and I still struggle with that, and I'm not sure I have any answers for it. But I try to avoid polypharmacy as much as we can. We had a number of people who moved to Colorado on 5, 7, 8, medications and we had to just reduce medications to even think about adding something new in. But that is one of the things that I haven't quite figured out with stiripentol, is how much can we get away from polypharmacies? If we're using stiripentol and fenfluramine, does that mean we're obligated to use 4 medications? I don't know the answer to that, but I always feel that less medicine is better than more medicine.

Joseph E. Sullivan, MD: Right, I agree. And I would say meaning if you look at all these trials, if you look at the median number of background medications that the study medication is added to, it is kind of 2 to 3 which means they're on 3 to 4. And I always even say to my residents and fellows, "If you're adding a fourth medicine, you have to acknowledge that first medicine, you've added the second, the third, what role is that first medicine playing?" And it just gets into that comfort of being willing to take something away, acknowledging that could be wrong, it could be doing something and things may get worse. But unless you try, this is how you end up with someone on 6, 7, and 8. And in that same theme of polypharmacy, we talked about the sequential, obviously, we're adding on drugs because maybe we get some benefit, and then the benefit wears off. The dreaded honeymoon effect which, in my opinion, I don't think any drug is immune to the honeymoon effect. Some may be less than others, but I'm wondering how do you talk about that with families? And I'm wondering, Mary Anne, does that, do you almost go into it with that expectation? Like, "Yeah, this is going to work for a short period of time, but it's only a matter of time before it wears off." Kelly, maybe you go first, do you talk about the honeymoon effect, or do you try to be the optimist and not go there?

Kelly Knupp, MD: Early on, with a younger patient, I probably don't talk much about the honeymoon effect. But I find that my older patients, they may not call it the honeymoon effect, but the families describe it. They're like, "That worked for 6 months and then stopped working – that worked for 8 months and then stopped working." So, putting a name on it helps us talk about it a little bit more. But Mary Anne, I'd love to hear your perspective on that.

Mary Anne Meskis: It's very similar, when Elliot was diagnosed in 2004, and you Googled dravet syndrome and there were 3 hits. And one of them happened to be this small Yahoo support group, and so I was fortunate to connect with families who were a little further down along the path than we were. And what a lot of them said is they kind of found with those core medications were they'd had the most impact for their child and when they tried these other ones that they thought might have an effect, usually, if they saw that honeymoon period happen within 3 to 6 months, they knew it wasn't worth them staying on them. Because they knew it was not going to be long-term like some of the other ones. And our situations certainly mirrored that as well, so, we found with Elliot, there are 3 medications that seemed to attack his different seizure types and it was beneficial for us to continue on those. Even if we gave a try to other medications along the way.

Transcript Edited for Clarity

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