Epilepsy care keeps advancing on multiple fronts — new antiseizure medications with novel mechanisms, precision neuromodulation, and better imaging for surgical planning. Around a third of people with focal epilepsy still have seizures despite sequential drug trials, which is what drives the search for genuinely new mechanisms.
Pharmacologic advances
Fenfluramine substantially reduces convulsive seizures in Dravet syndrome and drop seizures in Lennox-Gastaut syndrome. Cenobamate produces notably high responder rates in drug-resistant focal epilepsy, with a meaningful proportion of patients achieving near-complete seizure control. Cannabidiol (Epidiolex) is approved for Dravet, Lennox-Gastaut, and tuberous sclerosis complex. Ganaxolone (Ztalmy), a neurosteroid acting on GABA receptors, is approved for CDKL5 deficiency disorder and in trials for TSC. Common tolerability issues across these agents include somnolence, dizziness, and reduced appetite.
The key new development is azetukalner (formerly XEN1101), a first-in-class, once-daily Kv7.2/7.3 potassium channel opener — a mechanism structurally distinct from existing drugs. In the Phase 3 X-TOLE2 trial in highly treatment-resistant focal epilepsy, azetukalner cut monthly seizures by a median 53% at the higher dose versus about 10% with placebo, with dizziness the most common adverse effect; a regulatory submission is anticipated. If approved, it would be the first drug of its class for epilepsy.
Minimally invasive and neuromodulation therapies
Laser interstitial thermal therapy (LITT) achieves meaningful seizure freedom in mesial temporal lobe epilepsy with lower complication and reoperation rates than older ablative approaches, and shorter recovery. Deep brain stimulation (DBS) and responsive neurostimulation (RNS) deliver substantial, durable seizure reductions in drug-resistant focal epilepsy, with DBS of the centromedian thalamic nucleus showing promise in pediatric refractory epilepsy.
Surgery and imaging
Resective surgery remains the gold standard for well-localized, drug-resistant epilepsy, with the highest seizure-free rates in mesial temporal lobe epilepsy — though minimally invasive techniques are increasingly chosen for their lower morbidity. Stereoelectroencephalography (SEEG) and tractography have sharpened localization and surgical planning, improving outcomes while reducing adverse effects; early surgery, a clearly defined MRI lesion, and complete resection remain the strongest predictors of success.
| Modality | Main indication | Efficacy | Notes |
|---|---|---|---|
| Fenfluramine | Dravet, LGS | Marked seizure reduction | Approved |
| Cenobamate | Focal DRE | High responder rate | Approved |
| Cannabidiol | Dravet, LGS, TSC | Meaningful reduction | Approved |
| Azetukalner | Focal DRE | ~53% median reduction (Phase 3) | First-in-class Kv7 opener; filing anticipated |
| LITT | MTLE, focal | Good seizure freedom | Minimally invasive |
| DBS / RNS | Drug-resistant focal | Substantial, durable reduction | Multiple targets |
| Resective surgery | Localized DRE | Highest seizure-free rates | Best if lesion well-defined |
Further reading: azetukalner X-TOLE2 (Xenon, 2026); LITT meta-analysis (Mohsen et al., 2025); ANT-DBS vs RNS (Yang et al., Epilepsia 2022); mesial temporal lobe epilepsy intervention review (Marathe et al., 2021).