What is the new drug for epilepsy? Recent breakthroughs
The landscape of epilepsy treatment has evolved significantly, offering renewed hope for patients, especially those with drug-resistant forms of the condition. While there isn't a single 'newest' drug for all types of epilepsy, several medications have recently gained FDA approval or expanded indications. These newer options, such as cenobamate (Xcopri), fenfluramine (Fintepla), and ganaxolone (Ztalmy), represent substantial progress by targeting new mechanisms in the brain. Alongside these systemic therapies, newer rescue medications like diazepam nasal sprays and innovative monitoring devices are also transforming care.
Noteworthy recent FDA-approved epilepsy medications
- Cenobamate (Xcopri): Approved in November 2019 for the treatment of focal-onset seizures in adults, cenobamate has been described as a "game-changer" by many neurologists. It is known for its high efficacy, particularly in patients with treatment-resistant epilepsy. Its approval was based on clinical trials showing significant reductions in seizure frequency, with some patients achieving complete seizure freedom.
- Fenfluramine (Fintepla): Initially approved for Dravet syndrome, its indication was expanded to include seizures associated with Lennox-Gastaut syndrome (LGS). Fenfluramine works through a distinct mechanism by modulating serotonin and sigma-1 receptors, and has shown efficacy in managing challenging seizure types, including drop seizures.
- Ganaxolone (Ztalmy): This medication was approved in 2022 for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a rare genetic form of epilepsy. Ganaxolone is a positive allosteric modulator of GABAA receptors, a mechanism that provides enhanced neuronal inhibition.
- Diazepam buccal film (Libervant): In April 2024, the FDA approved this buccal film formulation for the acute treatment of seizure clusters in pediatric patients with epilepsy aged 2 to 5 years. It offers a non-invasive and convenient alternative to rectal administration for emergency situations.
- Diazepam nasal spray (VALTOCO): An expanded indication was approved in April 2025 for use in children aged 2 to 5 for the treatment of seizure clusters. This intranasal rescue therapy is an important advancement for providing rapid treatment in community and home settings.
Mechanisms of action for new epilepsy drugs
The most significant aspect of these new drugs is their novel mechanisms, which provide options for patients who do not respond to traditional antiepileptic medications. Instead of relying on a single pathway, these newer treatments often modulate multiple neural targets.
- Cenobamate's dual action: Cenobamate works via two distinct pathways. It acts as a positive allosteric modulator of GABAA receptors, increasing inhibitory currents in the brain, and it also inhibits persistent sodium currents, which reduces neuronal excitability. Its specific inhibition of the persistent sodium channel, while sparing the transient sodium channel, is a unique feature that may contribute to its high efficacy.
- Fenfluramine's serotonergic effects: Fenfluramine and its metabolite, norfenfluramine, increase serotonin release and reduce its reuptake. They also act on various serotonin receptor subtypes and the sigma-1 receptor, providing a distinct and multi-faceted mechanism to combat seizures in specific syndromes like Dravet and LGS.
- Ganaxolone's GABAA modulation: Ganaxolone enhances the activity of both synaptic and extrasynaptic GABAA receptors. This broader modulation offers a more persistent inhibitory effect compared to some benzodiazepines that primarily target synaptic receptors.
Comparison of key epilepsy medications
| Feature | Cenobamate (Xcopri) | Fenfluramine (Fintepla) | Ganaxolone (Ztalmy) | Lacosamide (Vimpat) |
|---|---|---|---|---|
| Mechanism | Dual: Modulates GABAA receptors; Inhibits persistent sodium currents | Dual: Modulates serotonin and sigma-1 receptors | Modulates synaptic and extrasynaptic GABAA receptors | Selective inhibition of voltage-gated sodium channels |
| Primary Indication | Focal-onset seizures (adults) | Dravet syndrome & Lennox-Gastaut syndrome | CDKL5 deficiency disorder (CDD) | Focal-onset seizures (adults & children ≥4) |
| Formulation | Oral tablets | Oral solution | Oral suspension | Oral tablets, solution, and IV |
| Recent FDA Status | Label updates in 2024 & 2025 | Label updates in 2025 | Label updates in 2025 | Broadened pediatric indication in 2021 |
| Common Side Effects | Dizziness, fatigue, sleepiness | Decreased appetite, fatigue, sedation | Drowsiness, fatigue, dizziness | Dizziness, headache, nausea |
The future of epilepsy treatment and managing side effects
Research and development in epilepsy extend beyond pharmaceuticals into innovative medical devices and personalized medicine. Implantable devices, such as responsive neurostimulation and continuous EEG monitors like Epiminder's Minder, which received FDA authorization in April 2025, offer new approaches for monitoring and controlling seizures. Furthermore, advances in gene and cell therapy are being explored, which could lead to more targeted and potentially curative treatments in the future.
When considering new medications, managing side effects is a crucial part of treatment. Most antiepileptic drugs, including newer ones like cenobamate, carry risks of adverse effects such as drowsiness, fatigue, and dizziness. Cenobamate requires a slow titration schedule to minimize the risk of a severe allergic reaction known as DRESS syndrome. Fenfluramine was withdrawn in the past due to cardiac risks associated with its use as an appetite suppressant, but it was reintroduced at lower doses and under strict monitoring for its antiepileptic properties. The benefit-risk profile for any new drug must be carefully weighed by a physician in consultation with the patient.
Conclusion
While there is no single new drug for epilepsy that cures all cases, the array of recent advancements offers significant progress, especially for those with hard-to-treat forms of the condition. Cenobamate, fenfluramine, and ganaxolone, with their novel mechanisms, provide effective new options for specific patient populations. The ongoing development of innovative delivery systems and device-based therapies further expands the therapeutic landscape. Patients and caregivers should work closely with their neurologists to discuss these new treatments and determine the best course of action based on their specific type of epilepsy and individual needs. A key resource for staying up-to-date on FDA alerts and new drugs is the American Epilepsy Society.
