Key messages
- When added to one or more antiseizure medications, cenobamate is probably better than placebo (sham medical treatment) in reducing the frequency of epileptic seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy who do not respond to long-term antiseizure medications.
- Cenobamate use probably causes more unwanted effects than placebo.
What was studied in this review?
Epilepsy is a disease of the brain where there is a recurrence of epileptic seizures. With the currently available antiseizure medications, approximately 7 out of 10 people with epilepsy can have their seizures controlled. However, 3 out of 10 people with epilepsy do not respond to medication and continue to have seizures. Cenobamate is a new drug developed to treat people with epilepsy that does not respond to antiseizure medications.
What did we want to find out?
We wanted to know if cenobamate is effective in reducing the risk of epileptic seizures when added to other antiseizure medications in people with drug-resistant focal epilepsy (a type of epilepsy where the main symptom is recurring seizures that affect one side of the brain) who continue having seizures despite taking antiseizure medications.
What did we do?
We searched the medical literature for studies that looked at the effect of cenobamate as an add-on drug compared to placebo or another antiseizure medication.
What did we find?
We found two studies (659 people, aged 18 to 70 years) comparing add-on cenobamate versus placebo in adults with uncontrolled focal epilepsy.
Seizure frequency was reduced if cenobamate was added to usual treatment. People treated with 100 mg to 400 mg/day of cenobamate were more likely to experience at least a 50% reduction in the frequency of their seizures and were more likely to become seizure-free. However, adding cenobamate to usual treatment resulted in an increased risk of unwanted effects (particularly with dosages of 200 mg/day or 400 mg/day, compared to cenobamate 100 mg/day).
What are the limitations of the evidence?
We are only moderately confident in the evidence because the evidence came from only two trials that were funded by the drug company that produces cenobamate.
How up‐to‐date is the evidence?
The evidence is current to September 2022.
Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.
Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs.
To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs.
We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies.
RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs.
Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table.
We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence).
We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate.