Medication Options for
KCNT1-Related Epilepsy
Why “one and done” rarely works with KCNT1
Medication and Treatment Approaches for KCNT1-Related Epilepsy
Children with KCNT1-related epilepsy often require multiple anti-seizure medications (ASMs) due to the drug-resistant nature of their seizures. Treatment must be tailored to the individual child, the seizure type, and their genetic profile. Some children may benefit from newer or alternative treatments like cannabidiol (CBD) or the ketogenic diet, while others may experience side effects or worsening of symptoms on standard medications.
There is no single medication that works for all individuals with KCNT1-related epilepsy. Patients typically try multiple anti-seizure medications, often in combination. While many do not achieve full seizure control, a subset of children may experience partial or temporary seizure reduction with existing treatments.
Common Anti-Seizure Medications
Common Anti-Seizure Medications
Medications designed to suppress abnormal electrical activity in the brain and reduce seizure frequency.
Many children with KCNT1-related epilepsy are prescribed standard anti-seizure medications such as phenobarbital, levetiracetam, valproate, topiramate, and zonisamide. These are often tried in various combinations. While some families report improvement, most children with KCNT1 gain-of-function mutations do not experience complete seizure control with these medications alone. (Gras et al., 2024; Survey of KCNT1 patients)
First-Line and Commonly Used Medications by Seizure Type
Each medication listed below is based on published use in KCNT1-related epilepsy or developmental and epileptic encephalopathies (DEEs). Responses are highly variable and no one treatment works for everyone.
Tonic, Focal, or Migrating Seizures
Phenobarbital
Often used early in neonatal settings; long-acting.
Levetiracetam (Keppra)
Widely prescribed; generally well tolerated.
Topiramate (Topamax)
Used for focal or generalized seizures.
Clobazam (Onfi)
Benzodiazepine often added as adjunct therapy.
Carbamazepine or Oxcarbazepine
Sometimes used in ADSHE/SHE but not generally preferred in early-onset KCNT1 due to risk of seizure aggravation in some cases.
Infantile Spasm Syndrome
ACTH or Prednisolone
First-line treatments for Infantile Spasm Syndrome (sometimes called West Syndrome). In KCNT1-related epilepsy, there is no clear evidence that ACTH is more effective than prednisolone, and access to ACTH may be limited in some regions.
Vigabatrin (Sabril)
First-line treatments.
Myoclonic or Generalized Seizures
Valproic Acid (Depakote)
Broad-spectrum ASM.
Zonisamide
Used as adjunctive therapy.
Lamotrigine (Lamictal)
Broad-spectrum, but watch for skin reactions and potential pharmacogenomic interactions (see below).
Rescue Therapies for Clusters or Status Epilepticus
Diazepam rectal gel (Diastat)
Emergency rescue medication administered rectally to stop prolonged seizures or clusters.
Valtoco or Midazolam nasal spray
Fast-acting nasal spray for emergency seizure management. (ages 2+)
Lorazepam (Ativan)
IV or oral; commonly used in hospitals for acute seizure management.
Cannabidiol (CBD)
Cannabidiol (CBD)
A compound derived from cannabis, used in pharmaceutical form (e.g., Epidiolex) to treat certain types of epilepsy.
Cannabidiol, including the FDA-approved drug Epidiolex, is sometimes used in KCNT1 patients. While evidence is still limited, 8 out of 17 children in the Gras et al. (2024) study experienced improvement in seizures. Dosing should be carefully managed, and families should consult with neurologists familiar with CBD treatment.
Benzodiazepines
A class of medications that act as central nervous system depressants and may be used for seizure emergencies or maintenance.
Drugs like clonazepam or diazepam are occasionally prescribed, although effectiveness varies. Some families report temporary improvement, but long-term use is limited due to sedation and tolerance.
Repurposed Drugs
Repurposed medications being explored for their potential to reduce neuronal hyperexcitability in KCNT1 gain-of-function mutations.
Fluoxetine (an SSRI) and carvedilol (a beta-blocker) have been tested in lab studies and limited patient reports. One case study showed marked clinical improvement with fluoxetine (PubMed ID: 38644974). Both drugs are being explored as potential potassium channel modulators.
Ketogenic Diet
A high-fat, low-carbohydrate diet that helps control seizures in some people with epilepsy.
The ketogenic diet has shown benefit for many individuals with KCNT1-related epilepsy. In a 2024 study, 13 out of 24 patients reported seizure improvement while on the diet (Gras et al., 2024). It may be trialed under medical supervision, especially in early-onset epilepsies where seizures are resistant to medications.
In some countries, medical pre-made, commercially available ketogenic diet infant formulas are accessible. Infants can do well on these formulas when prescribed and closely monitored by a medical team.
Investigational Therapies
Emerging treatments specifically targeting the genetic basis of KCNT1 epilepsy.
Several targeted therapies are in development, including:
- Small molecule inhibitors: Tailored compounds that reduce overactive KCNT1 channel activity.
- Antisense oligonucleotides (ASOs): RNA-based treatments aimed at suppressing mutant KCNT1 expression.
- siRNA and gene therapy approaches are also being explored.
These therapies are not yet approved, but clinical trials are expected to begin soon. Stay connected to the KCNT1 Foundation for updates. For more information see our page on Current and Emerging Treatments.
What parents need to remember
Adjustments are the norm.
Growth spurts, illness, and puberty all change drug levels regular bloodwork and diary reviews keep doses on target.
Match the med to the seizure.
Giving a focal-only drug for spasms (or vice-versa) wastes time and adds side-effects. Track seizure types so your neurologist can match the right tool to the job.
Watch for sedation & behavior shifts.
Many KCNT1-friendly meds (clobazam, topiramate) can cause drowsiness, irritability, or appetite change; report any sharp swings.
Polytherapy is common.
Because KCNT1 children often have more than one seizure type, stacking medications at lower doses can control seizures with fewer side effects than a single drug.
Rescue meds are separate.
Daily drugs prevent seizures; rescue meds stop an emergency. Never swap one for the other.
Stay trial ready.
Keep EEGs, genetic reports, and detailed seizure logs current sponsors will ask for baseline data when KCNT1 trials launch.
Always discuss changes with your child’s neurologist—this guide is for education, not a prescription.
Quick Guide
| Category | Purpose & When Used | Typical Options | Key Points for KCNT1 |
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| Daily Seizure control (maintenance meds) | Taken every day to reduce overall seizure burden |
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| Infantile spasm specific meds | Target the rapid “jack-knife” clusters seen in babies |
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| Rescue / emergency meds | Given during a seizure > 5 min or a dangerous cluster |
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| Diet & device options |
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| Investigational & coming soon | Research aiming to fix the “broken traffic light” itself |
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Personalizing Medication Choices
Personalizing Medication Choices
Some families have explored pharmacogenomic (PGx) testing to help guide medication decisions.
What is PGx testing? Pharmacogenomic (PGx) testing is a genetic test that may help predict how rapidly or slowly a child’s body will metabolize a specific medication or class of medications. It is not widely used in pediatric epilepsy yet, but may be helpful in certain cases. It may allow a clinician to infer whether or not a lower or higher dose may be needed to generate a therapeutic blood level. Common misconception: it does NOT predict efficacy. The most common use scenario is to help families avoid side effects by understanding if the child is a slow metabolizer.
- PGx testing can sometimes help reduce side effects by selected a dose level that works better
- Results can apply to future medications, not just current ones
Ask your child’s care team whether PGx testing could be useful, especially if your child has tried many medications with limited success. Download our PGx Testing Guide for KCNT1-Related Epilepsy.
References:
Seizure Aggravation—Evidence That Oxcarbazepine Requires Monitoring
https://pmc.ncbi.nlm.nih.gov/articles/PMC2442149
Written by KCNT1 Epilepsy Foundation Research Team. Reviewed by a Pediatric Neurologist. December 30, 2025
