Seizures Continuing Despite Medication? What It Can Mean
About 2.9 million U.S. adults live with active epilepsy, and roughly 1.5 million of them reported seizures in the past year that were not under control, according to the CDC. If you are one of them, you are far from alone, and you have more options than you may have been told.
Key takeaways
About one in three people with epilepsy continue to have seizures despite medication, according to the International League Against Epilepsy (ILAE).
Ongoing seizures can come from missed doses, triggers, the wrong medicine for the seizure type, or epilepsy that resists medication.
A comprehensive epilepsy center can confirm the diagnosis and look at options beyond another pill.
Two Phase 3 studies of an investigational medicine, X-ACKT and X-TOLE3, are enrolling people whose seizures continue despite treatment.
Why seizures can continue even when you take your medicine
Ongoing seizures do not always mean the medicine has "failed." Neurologists usually work through these possibilities in order:
Missed or late doses. Even a few hours late can matter for some medicines. We cover practical fixes in our guide to breakthrough seizures.
Triggers. Lack of sleep, alcohol, illness, stress and interactions with other medicines can all lower the seizure threshold.
A medicine that does not match the seizure type. Some medicines that work for focal seizures can be less helpful, or even make things worse, for certain generalized seizures. Read how focal and generalized seizures differ.
Events that are not epileptic. Fainting, heart rhythm problems and psychogenic non-epileptic seizures can look like epilepsy. Video-EEG monitoring can tell them apart.
Drug-resistant epilepsy. When two well-chosen, well-tolerated medicines at adequate doses have not led to lasting seizure freedom, the ILAE calls it drug-resistant epilepsy.
What a specialist will look at
If seizures continue after two medicines, many experts recommend a referral to a comprehensive epilepsy center. There, a team may review:
Your seizure diary shows frequency, patterns and triggers over time. See our seizure diary guide.
Video-EEG monitoring records seizures on video alongside brain activity to confirm the type and where they start.
A brain MRI looks for a structural cause that might be treated with surgery.
Your medicine history, meaning every medicine, dose and side effect you have had, so the team avoids repeating what did not work.
Other conditions, because sleep, mood, other medicines and hormones can all affect seizure control.
Depending on the findings, options may include a different medicine combination, epilepsy surgery evaluation, neurostimulation devices, dietary therapy under medical supervision, or a clinical trial.
Tried two or more seizure medicines and still having seizures? Two research studies are enrolling now.
Two Phase 3 studies enrolling now
Researchers are testing XEN1101 (azetukalner), an investigational medicine, as an add-on to the seizure medicines people already take. Two studies are enrolling, each for a different seizure type:
Study snapshot: two Phase 3 epilepsy studies
What is being studied
XEN1101 (azetukalner), an investigational once-daily capsule taken with the evening meal. It is designed to act on Kv7 potassium channels, which help calm overactive electrical signals in brain cells.
How it is tested
Added to a person's current seizure medicines and compared with placebo in a randomized, double-blind design. A baseline period of up to about 9.5 weeks is followed by 12 weeks of blinded treatment.
X-ACKT (NCT05667142)
People aged 12 and older with generalized epilepsy who have primary generalized tonic-clonic seizures, have tried at least two seizure medicines, and currently take 1 to 3.
X-TOLE3 (NCT05716100)
Adults aged 18 and older with focal epilepsy diagnosed at least two years ago, who have tried at least two seizure medicines and currently take 1 to 3.
After the blinded period
People who complete the 12 weeks may be able to join a separate open-label extension study, where everyone receives XEN1101.
Where
X-ACKT has dozens of research sites across the U.S., including epilepsy centers in Boston, Philadelphia, Atlanta, Houston, Cleveland, Seattle and Los Angeles. The study team can tell you the nearest site for either study.
Examples of reasons someone may not be eligible include status epilepticus in the past year, psychogenic non-epileptic seizures, certain epilepsy syndromes such as Lennox-Gastaut syndrome, or seizures caused by drugs, alcohol or a progressive brain condition. The study team reviews every person individually.
What checking your eligibility involves
Answer a short questionnaire about your seizure type, diagnosis date and medicines. Not sure of your seizure type? That is fine, there is an option for that.
Talk with the study team. If you may be a match, a nearby site contacts you and answers your questions.
Review the informed consent form, which explains visits, possible risks, the chance of receiving placebo and your right to leave at any time.
Complete screening, including a baseline period where you record your seizures in a diary.
Never stop seizure medicine on your own
Stopping or changing antiseizure medicine suddenly can trigger severe seizures, including status epilepticus. Make any change only with your neurologist.
Frequently asked questions
Why do I still have seizures if I take my medication every day?
Common reasons include triggers such as poor sleep or illness, a medicine that does not fit your seizure type, events that are not epileptic, or drug-resistant epilepsy. A neurologist or epilepsy center can help sort out which applies.
What is drug-resistant epilepsy?
The ILAE defines it as epilepsy in which two tolerated, appropriately chosen and used antiseizure medicine schedules have not achieved sustained seizure freedom.
What is XEN1101?
XEN1101, also called azetukalner, is an investigational once-daily medicine being studied as an add-on to existing seizure medicines. Its safety and effectiveness are still being evaluated in clinical trials.
Will I have to stop my current seizure medicines to join?
No. Both studies test XEN1101 or placebo added to a stable dose of 1 to 3 current seizure medicines. Never change your medicines without your neurologist.
Can teenagers join?
The X-ACKT study includes people aged 12 and older with primary generalized tonic-clonic seizures. The X-TOLE3 study is for adults aged 18 and older with focal epilepsy.