News

Article

Optimizing Epilepsy Treatments: Stiripentol’s Role in Dravet Syndrome

Author(s):

Key Takeaways

  • Stiripentol is a well-established anticonvulsant for Dravet syndrome, approved in Europe and the U.S., offering versatile formulations and no REMS requirement.
  • Early genetic testing and diagnosis of Dravet syndrome are crucial for preventing irreversible cognitive and developmental damage.
SHOW MORE

James Wheless, MD, FAAP, FAAN, FAES, Le Bonheur Chair in Pediatric Neurology at the University of Tennessee Health Science Center, shared insights on his presentation from AES 2024, focusing on stiripentol, an FDA-approved treatment for Dravet syndrome.

James Wheless, MD, FAAP, FAAN, FAES

James Wheless, MD, FAAP, FAAN, FAES

Stiripentol (Diacomit; Biocodex) is an anticonvulsant medication primarily used as an adjunctive therapy for Dravet syndrome (DS), a rare and severe form of genetic epilepsy. Discovered in the late 1970s and early 1980s by French researchers, stiripentol was initially developed and tested for its broad anticonvulsant properties. Over the decades, its unique mechanism of action and significant efficacy in drug-resistant epilepsy, particularly DS, became apparent.

The medication has been used in Europe for decades, where it was approved in 2007 for the treatment of DS in children. It then received FDA approval in the United States in 2018 for use in children aged 2 years and older with DS. Marking an important milestone for the epilepsy community.

At the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10, in Los Angeles, California, epilepsy expert James Wheless, MD, FAAP, FAAN, FAES, gave a presentation on the optimization of stiripentol and DS treatments. Following his presentation, Wheless sat down with NeurologyLive® to give greater insights on the talk, and the unique treatment guidelines for DS. Wheless, professor and chief of pediatric neurology and the Le Bonheur Chair in Pediatric Neurology at the University of Tennessee Health Science Center, discussed the therapeutic advantages of stiripentol, as well as explored ways to optimize and personalize the treatment. Furthermore, he touched on advancements in diagnosing and treating DS, including the role of genetic testing and the importance of early intervention to preserve cognitive and developmental outcomes.

NeurologyLive: What was the main takeaway from your presentation?

James Wheless, MD, FAAP, FAAN, FAES: I think the key takeaway is that Dravet syndrome is unique in that it’s an epilepsy where we actually have clear treatment guidelines and a structured path to follow. For most epilepsies, we have a lot of treatment options, but we don’t say, “Start here, then go to the next step, and then the next step.” With Dravet, we have very clear international guidelines and limited treatment options, which helps clinicians cut through the sea of treatment choices for epilepsy and really focus on this specific disease.

Coupled with that, we now have strong data showing that if you use those treatments, your patients do better. This is a devastating epilepsy, and by helping with their seizures, you’re likely minimizing their risk of death—which is huge. I tell my patients, "Yes, you have a bad form of epilepsy, and that’s awful. But at the very least, you should be on a treatment that keeps you alive."

What are some of the therapeutic advantages of stiripentol?

One of the things that makes stiripentol easier to use is that it’s FDA-approved specifically for this indication, and it comes in formulations we can use with different types of patients. If a patient can swallow pills, we have a pill form. If not, there’s a powder that can be mixed into a liquid. So it’s versatile and adaptable to patient needs.

Another advantage is that there’s no required REMS program, so it’s easier to get through specialty pharmacies. Interestingly, while specialty pharmacies used to be a nightmare early on, in the modern world, they’ve become much smoother to work with. Many of my patients actually prefer specialty pharmacies over their local Walgreens or CVS because their medications show up in the mail, on time, without gaps.

Additionally, stiripentol isn’t a new drug—it’s been used in Europe, particularly in France, for over 30 years. So while it’s relatively new to us in the U.S., it’s a well-established compound. There are no surprises with this drug; we know what to expect, and the data supporting its use is solid.

How can we continue to optimize and personalize stiripentol?

If I were in charge of improving stiripentol, there are a few things I’d focus on. First, the drug is really susceptible to acid degradation in the stomach, so it has to be taken with food. Clinicians and patients need to be reminded of this constantly—especially for the evening dose, which should probably be taken with dinner, not at bedtime on an empty stomach.

Second, while the powder formulation is helpful, it would be ideal to have a pre-made liquid version. Parents can measure powders, but it can be tricky. There’s always a question of whether they’re measuring it exactly right. If it came as a liquid suspension or, even better, an extended-release liquid, it would be much more convenient and ensure consistent levels throughout the day.

Ultimately, stiripentol is a great drug, but we can make it easier for families to use and improve its efficacy just by enhancing the delivery system.

Over the years, what improvements have been made in recognizing, diagnosing, and treating Dravet syndrome more efficiently?

Before we had a genetic marker for Dravet, it was very much a clinical diagnosis. And while we still rely on clinical evaluation, we now combine it with genetic testing. Back when I started, you didn’t want to give a patient and their family a diagnosis of Dravet unless you were very confident. Often, we wouldn’t make the diagnosis until the child was four or five years old, even if we suspected it earlier.

Thirty years ago, there wasn’t much urgency because we only had one treatment option, and it wasn’t very effective. But today, things are different. There’s much more awareness of the clinical phenotype, and we can do genetic testing to confirm the diagnosis early.

Early diagnosis is crucial because we know that waiting to treat these children negatively affects their cognition and development. If they experience prolonged convulsive seizures or febrile status early on, the damage is often irreversible. Starting effective treatment early can prevent this, and in the modern era, we’re usually able to secure these treatments for our patients.

Are there ways we can get more creative with drug development and clinical trials?

Using Dravet as an example, it’s the most common monogenic epilepsy, but there are over 900 other types of monogenic epilepsies. Dravet gets a lot of attention, but the big shift will be in developing genetically targeted treatments that modify the underlying disease.

Right now, we’re treating symptoms—primarily the seizures—but the disease itself has many other manifestations, like sleep problems, behavioral issues, cognitive delays, orthopedic problems, and GI issues. The seizures are just the first symptom that brings patients to medical attention.

With advances in technology and our understanding of genetics, we can start targeting the disease itself. The next big challenge will be figuring out how to safely deliver these genetic treatments to the brain. That’s where the future lies—not just in developing these treatments, but in ensuring they’re effective and easy to administer.

What excites you about this year’s AES meeting?

Every year, the AES meeting has a different flavor. There are always new advances, which is great because our patients need hope, and they need us to keep moving the needle forward.

This year, I’ve noticed a lot of focus on patients with devastating epilepsies—those who are often left on the fringes. It’s not to say that other forms of epilepsy aren’t serious, but these patients face particularly severe challenges. It’s great to see more discussions and research centered on them, as it shows we’re prioritizing ways to lift them up and improve their care.

Transcript edited for clarity. Click here for more AES 2024 coverage.

Related Videos
 Betty Bigio, PhD; Carla Nasca, PhD
 Christina J. Azevedo, MD
Phillip Kuo, MD
Jacquelyn Bainbridge, PharmD, BSPharm, FCCP, MSCS, FAES
Joseph Kuchling, MD
2 experts in this video
© 2025 MJH Life Sciences

All rights reserved.