Cenobamate: a new drug that may change the concept of drug-resistant focal epilepsy.

INTRODUCTION: Despite the constant approval of new antiseizure medications in recent years, the percentage of patients whose epilepsy is not fully controlled remains stable, at approximately 30%-40% of cases. This is because the newly approved drugs, despite providing benefits in terms of tolerability, ease of use, and reduction of pharmacokinetic interactions, have not achieved greater efficacy against seizures than previous drugs.

DEVELOPMENT: Cenobamate has changed this scenario. Both in clinical trials and clinical practice series, it has achieved hitherto unseen seizure freedom rates in patients showing no response to 2 or more drugs. Its tolerability is similar to that of its predecessors. The most frequently reported adverse reactions include somnolence, dizziness, headache, fatigue, and diplopia. In general, they were mild or moderate in intensity, with a tendency to decrease with time. To avoid these as far as is possible, proper management of polymedication is important, especially in patients with a high pharmacological burden when cenobamate is introduced. Given its action mechanism, the most relevant pharmacodynamic interactions will involve other voltage-dependent sodium channels and benzodiazepines, especially clobazam.

CONCLUSION: Considering the response rates obtained, cenobamate may change the concept of drug-resistant epilepsy. Failure of any 2 drugs will no longer be sufficient to define this condition; rather, it will require failure of the most efficacious drug.