Exploring What are the New Seizure Medications?

October 7, 2025 •

4 min read

Approximately one-third of epilepsy patients are resistant to older anti-seizure medications, driving the development of new treatments with novel mechanisms and better side-effect profiles. Exploring what are the new seizure medications reveals significant advancements that offer renewed hope for improved seizure control and quality of life.

Quick Summary

An examination of recent advancements in epilepsy treatments highlights several new medications and therapies for various seizure types. Key recent approvals include cenobamate, fenfluramine, and ganaxolone, targeting refractory and rare forms of epilepsy. Investigational drugs and novel mechanisms are also emerging to improve seizure control and tolerability.

Key Points

Cenobamate (Xcopri): Approved for focal-onset seizures in adults, this drug works through a dual mechanism involving sodium channel inactivation and positive GABA-A modulation, demonstrating high efficacy in reducing seizure frequency.
Ganaxolone (Ztalmy): As the first approved treatment specifically for CDKL5 deficiency disorder (CDD) seizures, ganaxolone targets GABA-A receptors and offers significant benefits for this rare pediatric condition.
Fenfluramine (Fintepla): Initially used for appetite control, this medication was repurposed for severe epilepsy syndromes like Dravet and Lennox-Gastaut, requiring mandatory cardiac monitoring due to potential side effects.
Brivaracetam (Briviact): A newer alternative to levetiracetam (Keppra), brivaracetam offers a faster titration schedule and potentially fewer psychiatric side effects, though it is a controlled substance.
Investigational Drug XEN1101: Currently in Phase 3 trials, XEN1101 shows promise for treatment-resistant focal epilepsy by acting as a Kv7 potassium channel opener.
Novel Therapies: Beyond new medications, ongoing research includes advanced therapies like responsive neurostimulation (RNS), deep brain stimulation (DBS), and genetic and cellular treatments for hard-to-treat epilepsies.

An Evolving Landscape in Epilepsy Treatment

For decades, epilepsy treatment relied on a limited number of anti-seizure medications (ASMs). While effective for many, these drugs often came with significant side effects or failed to control seizures in a substantial portion of the patient population. The last decade has seen a surge in research and development, leading to FDA approval of several new medications with novel mechanisms of action, as well as promising drugs in clinical trials. These advancements provide neurologists with more options for personalized treatment plans, particularly for those with drug-resistant epilepsy or specific syndromes.

Cenobamate (Xcopri)

Approved by the FDA in 2019, Cenobamate is used to treat focal-onset seizures in adults. It is particularly notable for its efficacy in patients with drug-resistant epilepsy. Unlike many older ASMs, cenobamate operates through a dual mechanism:

Enhancing sodium channel inactivation: This reduces the high-frequency neuronal firing that characterizes a seizure.
Positive allosteric modulation of the GABA-A ion channel: This enhances the brain's natural inhibitory signals. In clinical trials, cenobamate demonstrated significant seizure reduction, with a notable percentage of patients achieving seizure freedom during the maintenance phase. Common side effects include dizziness, somnolence, and fatigue.

Ganaxolone (Ztalmy)

Ganaxolone is a neuroactive steroid and a positive allosteric modulator of GABA-A receptors. Its FDA approval in 2022 marked the first treatment specifically for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients two years of age and older. CDD is a rare genetic disorder causing severe early-onset epilepsy. The approval was based on trial data showing a statistically significant reduction in major motor seizures. Side effects often include somnolence and sedation, especially when used with other central nervous system depressants.

Fenfluramine (Fintepla)

Originally used for appetite suppression, fenfluramine has been repurposed and approved for treating seizures in specific syndromes: Dravet syndrome and Lennox-Gastaut syndrome (LGS) in patients aged two and older. Fenfluramine works by releasing serotonin and interacting with the sigma-1 receptor, among other actions. Its approval comes with a risk evaluation and mitigation strategy (REMS) program due to the risk of valvular heart disease and pulmonary hypertension, requiring regular cardiac monitoring. It is often used as an adjunctive therapy alongside other ASMs.

Brivaracetam (Briviact)

Brivaracetam is a newer drug in the same chemical class as levetiracetam (Keppra). Both medications target the synaptic vesicle protein 2A (SV2A) in the brain, though brivaracetam has a higher affinity for this site. Key differences exist between the two, which can influence a physician's choice:

Titration: Brivaracetam can often be started at the target dose, while levetiracetam requires a slower titration.
Behavioral Side Effects: Some studies suggest brivaracetam may cause fewer mood-related side effects, such as irritability, compared to levetiracetam.
Controlled Substance: Unlike levetiracetam, brivaracetam is a controlled substance, which is a consideration for patients with a history of substance misuse.

Investigational Therapies

Beyond recently approved drugs, the pipeline for novel epilepsy treatments includes promising candidates in clinical trials. These often explore new targets or delivery methods:

XEN1101 (Azito Kulner): A Kv7 potassium channel opener, XEN1101 showed significant seizure reduction in a Phase 2b trial for treatment-resistant focal epilepsy and was well-tolerated with once-daily dosing.
Gene and Cell Therapy: Researchers are exploring gene therapy to correct genetic defects causing epilepsy, such as in Dravet syndrome, and cell therapy involving the transplantation of inhibitory neurons to restore neural balance.
Advanced Neuromodulation: Devices like responsive neurostimulation (RNS) and deep brain stimulation (DBS) offer surgical alternatives for drug-resistant focal epilepsy, and research continues to expand their use.

Comparison of Key Newer Anti-Seizure Medications


Feature	Cenobamate (Xcopri)	Ganaxolone (Ztalmy)	Fenfluramine (Fintepla)	Brivaracetam (Briviact)
Primary Indication(s)	Focal-onset seizures (adjunctive) in adults	Seizures associated with CDKL5 deficiency disorder (CDD) in patients ≥2 years old	Seizures associated with Dravet syndrome and Lennox-Gastaut syndrome (adjunctive) in patients ≥2 years old	Focal-onset seizures (adjunctive)
Mechanism of Action	Sodium channel inactivation and GABA-A modulation	Positive allosteric modulation of GABA-A receptors	Serotonin release and sigma-1 receptor modulation	Binds to synaptic vesicle protein 2A (SV2A)
Patient Age	Adults	≥2 years old	≥2 years old	Varies by approval
Common Side Effects	Dizziness, somnolence, fatigue	Somnolence, sedation, fever	Decreased appetite, diarrhea, fatigue, cardiac risks	Somnolence, dizziness, fatigue
Special Considerations	Potential for serious skin reactions (DRESS), not for short QT syndrome	Monitor for sedation, drug interactions	REMS program for cardiac monitoring	Controlled substance, fewer mood changes than levetiracetam

Side Effect Considerations with New ASMs

While newer drugs often have improved tolerability compared to older ASMs, side effects are a common concern for many patients. As with any medication, side effects vary by individual and dosage. Patients on newer medications should be aware of potential issues, and open communication with their healthcare provider is key. Some common side effects across many ASMs include dizziness, fatigue, and mood changes. Serious but rare reactions, such as severe skin rashes (DRESS) or cardiac issues, are also potential risks that require careful monitoring, particularly with certain medications like fenfluramine. For this reason, a careful and well-informed medication recommendation is crucial for effective seizure control.

Conclusion

The array of what are the new seizure medications demonstrates a clear trend toward more targeted, mechanism-specific treatments. Recent approvals for Cenobamate, Ganaxolone, and Fenfluramine have brought new hope for patients with refractory epilepsy and rare genetic syndromes. Furthermore, the active pipeline of investigational drugs like XEN1101 and ongoing advancements in gene, cell, and neuromodulation therapies signal a future with even more personalized and effective options. These innovations empower clinicians to tailor therapy to individual patient needs, focusing not only on seizure reduction but also on improving overall quality of life.

For more information on epilepsy and treatment options, please consult the resources available from the Epilepsy Foundation.

Frequently Asked Questions

While multiple medications have been approved in recent years, some of the most recent approvals include ganaxolone (Ztalmy) for CDKL5 deficiency disorder in 2022 and fenfluramine (Fintepla) for Dravet and Lennox-Gastaut syndromes, with labeling updates in 2024 and 2025. Cenobamate (Xcopri) was approved for focal-onset seizures in adults in 2019.

Newer seizure medications often have more targeted and unique mechanisms of action. For example, cenobamate has a dual mechanism involving sodium channels and GABA-A receptors, while perampanel is an AMPA receptor antagonist, a different target than many older drugs. This can offer greater efficacy and potentially better tolerability.

While all medications have risks, many newer ASMs are designed to improve tolerability and reduce side effects compared to their older counterparts. Studies have shown newer drugs like lamotrigine are less likely to be discontinued due to side effects than older drugs like carbamazepine. However, serious but rare risks, such as cardiac issues with fenfluramine or allergic reactions, still exist with some newer drugs.

Yes. One of the most significant advances is the development of medications for rare genetic epilepsy syndromes. Examples include ganaxolone (Ztalmy) for CDKL5 deficiency disorder and fenfluramine (Fintepla) for Dravet syndrome and Lennox-Gastaut syndrome.

Common side effects for many newer ASMs include dizziness, somnolence, and fatigue. Specific drugs can have unique risks; for example, fenfluramine requires cardiac monitoring, and cenobamate carries a risk of serious skin reactions.

Both target the SV2A protein, but Brivaracetam has a higher binding affinity. A key clinical difference is that Brivaracetam can often be started at a target dose without a slow ramp-up, potentially offering faster seizure control. Some also report fewer mood-related side effects with Brivaracetam.

XEN1101, also known as azetukelner, is a promising investigational drug currently in Phase 3 clinical trials for treatment-resistant focal epilepsy. It works by opening Kv7 potassium channels and has shown positive results in earlier trials, suggesting potential future approval.