Psychiatric effects of cenobamate in adults with epilepsy: A retrospective study

To assess the psychiatric side effects of cenobamate (CNB) in adults with focal-onset drug-resistant epilepsy, evaluate its impact on pre-existing psychiatric comorbidities, and identify potential risk factors contributing to psychiatric symptom development.

This single-center, retrospective observational study included 60 patients who received CNB treatment for a minimum of six months. Clinical data, psychiatric history, and treatment outcomes were obtained through patient interviews and medical records. Psychiatric comorbidities were evaluated by experienced clinicians. Seizure outcomes and psychiatric effects were analyzed descriptively.

Cenobamate demonstrated high efficacy, with 12 % of patients achieving complete seizure freedom and 57 % experiencing a ≥50 % reduction in seizure frequency. No cases of new-onset psychiatric adverse effects were observed. Among the 22 patients presenting with psychiatric or behavioural symptoms at CNB initiation, 68 % showed no change at follow-up, 9 % experienced an improvement in their pre-existing psychiatric condition, and 23 % showed worsening of symptoms. All five patients with worsening symptoms had intellectual disabilities, exhibited irritability or aggressive behavior at baseline, and responded positively to seizure treatment. In contrast, none of the 13 patients with psychiatric or behavioural symptoms and normal cognitive profiles experienced any psychiatric deterioration.

Cenobamate did not induce new psychiatric side effects and was well tolerated in patients with pre-existing psychiatric conditions and normal intellectual functioning. However, in individuals with intellectual disabilities and baseline psychiatric comorbidities, CNB may exacerbate irritability through multifactorial mechanisms.