The development of new anti-seizure medications (ASMs), also known as antiepileptic drugs (AEDs), has dramatically expanded treatment options for people living with epilepsy. Unlike older drugs that often had broad, non-specific effects and significant side effects, newer generations of ASMs are often more targeted, better tolerated, and have fewer drug-drug interactions. This evolution is particularly crucial for the significant portion of the epilepsy population that does not achieve adequate seizure control with older therapies. The ongoing research and introduction of these new agents provide neurologists and patients with more tools to achieve the ultimate goal of complete seizure remission without debilitating side effects.
Key Recent Additions to the Pharmacopeia
Several medications with novel mechanisms of action have received FDA approval in the last few years, addressing different types of seizures and patient populations.
Cenobamate (Xcopri)
Cenobamate, approved in 2019, is used to treat partial-onset seizures in adults. It is notable for its high efficacy, even in patients resistant to multiple previous treatments. Its mechanism involves blocking voltage-gated sodium channels to stabilize brain activity, offering a new approach for those not responding to other sodium-channel blockers. Potential side effects include dizziness and fatigue, requiring gradual dose increases.
Brivaracetam (Briviact)
An analog of levetiracetam, brivaracetam was FDA-approved in 2016 for partial-onset seizures in adults and is now also approved for pediatric use. It binds to the synaptic vesicle protein 2A (SV2A) with higher selectivity than levetiracetam. Brivaracetam can often be started at a therapeutic dose quickly and may have fewer behavioral side effects compared to levetiracetam. It is approved for partial-onset seizures in patients one month and older.
Lacosamide (Vimpat)
Lacosamide is approved for expanded use in treating partial-onset seizures in patients aged 1 month and older and as adjunctive therapy for primary generalized tonic-clonic seizures in those aged 4 and older. Its mechanism is distinct, enhancing the slow inactivation of voltage-gated sodium channels. Available in various forms, including tablets and IV formulations, generic versions are also accessible.
Cannabidiol (Epidiolex)
Epidiolex is the first FDA-approved prescription, plant-derived cannabis medication. This purified oral formulation of cannabidiol (CBD) is thought to interact with the endocannabinoid system, but it does not cause psychoactive effects. It is approved for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex in patients one year of age or older, providing a crucial option for severe childhood epilepsies.
Expanding the Treatment Landscape
Ganaxolone (Ztalmy), approved in 2022, treats seizures associated with CDKL5 deficiency disorder. Diazepam Buccal Film (Libervant), approved in 2024, is an oral option for acute seizure clusters in certain pediatric patients. Emerging therapies, like NRTX-1001, a regenerative cell therapy, are also in clinical trials.
Comparing New Anti-Seizure Medications
| Medication (Brand Name) | Primary Mechanism | Approved Use(s) | Key Advantages | Common Side Effects | Schedule |
|---|---|---|---|---|---|
| Cenobamate (Xcopri) | Blocks voltage-gated sodium channels | Partial-onset seizures (adults) | High efficacy, even for refractory cases | Dizziness, fatigue, coordination issues | C-V |
| Brivaracetam (Briviact) | Binds to synaptic vesicle protein 2A (SV2A) | Partial-onset seizures (ages 1 month+) | Faster titration than levetiracetam, better mood tolerability | Somnolence, fatigue, dizziness, irritability | C-V |
| Lacosamide (Vimpat) | Enhances sodium channel slow inactivation | Partial-onset (ages 1 month+), PGTC (ages 4+) | Broad use, multiple formulations, generic available | Dizziness, headache, nausea, coordination issues | C-V |
| Cannabidiol (Epidiolex) | Modulation of endocannabinoid and other systems | LGS, Dravet, TSC (ages 1+) | Non-psychoactive, specific for severe syndromes | Somnolence, decreased appetite, liver enzyme elevation | Not controlled (purified) |
| Ganaxolone (Ztalmy) | Positive allosteric GABAA modulator | CDKL5 deficiency disorder (CDD) (ages 2+) | First FDA-approved drug for CDD | Somnolence, fatigue, sedative effects | N/A |
Advantages of Newer ASMs
Newer medications offer diverse mechanisms, improved tolerability, fewer drug interactions, and targeted treatment options compared to older therapies.
Important Considerations
Selecting treatment requires considering seizure type, age, comorbidities, and potential side effects. Gradual dosage adjustments may be needed. Abruptly stopping ASMs can increase seizure risk. Patients should be monitored for behavioral changes and suicidal thoughts, which are potential side effects.
Conclusion
The introduction of new anti seizure medications represents significant progress in epilepsy treatment. Medications like cenobamate, brivaracetam, and lacosamide offer improved efficacy and tolerability, while options like cannabidiol and ganaxolone target specific, challenging syndromes. For those with drug-resistant epilepsy, emerging therapies provide hope for better seizure control and quality of life. Consulting with a neurologist is key to tailoring a treatment plan using these newer options. For more information on epilepsy and treatment, visit the {Link: Epilepsy Foundation website https://www.epilepsy.com/}.
