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Cenobamate's effect on mood and seizure frequency.
Mert Karatas1, Alperan Yavuz2, Blake Newman2
1Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA; Molecular Medicine Program, University of Utah, Salt Lake City, UT 84112, USA.
Epilepsy & Behavior : E&B
|January 30, 2026
Summary
Cenobamate (CNB) effectively reduced seizure frequency in patients with epilepsy without worsening depressive symptoms. This real-world study indicates CNB is a safe and effective adjunctive treatment for seizure control.
Area of Science:
- Epilepsy and Neurological Disorders
- Pharmacology and Therapeutics
- Psychiatry and Mental Health
Background:
- Newly approved antiseizure medications (ASMs) require real-world efficacy and tolerability assessments, as these may differ from clinical trial findings.
- Approximately 40% of people with epilepsy (PWE) experience comorbid depression, necessitating evaluation of mood-related effects of new ASMs.
- Cenobamate (CNB) demonstrated significant efficacy in controlled trials, but its impact on mood in a real-world epilepsy population needs further investigation.
Purpose of the Study:
- To evaluate the real-world impact of adjunctive cenobamate (CNB) on mood, tolerability, and seizure control in adult patients with refractory focal epilepsy.
- To assess changes in depressive symptoms using Patient Health Questionnaire-9 (PHQ-9) scores.
- To analyze seizure frequency reduction and seizure freedom rates.
Main Methods:
- A single-center retrospective chart review of adult patients with refractory focal epilepsy initiating CNB as add-on therapy (May 2020-July 2023).
- Inclusion criteria: ≥3 months on CNB, available seizure frequency at baseline and follow-up, and paired PHQ-9 scores.
- Seizure outcomes analyzed by paired change, log2 fold-change, and percent change; response defined by seizure freedom, ≥50%, or ≥75% seizure reduction.
Main Results:
- 73 adult PWE met study criteria; median seizure frequency decreased from 5 to 1.5 per 30 days (p < 0.001), a 50% median reduction.
- 29% of patients achieved seizure freedom at the last follow-up (median 488 days).
- Patient Health Questionnaire-9 (PHQ-9) scores did not significantly worsen (median ΔPHQ-9 = 0), with no association between covariates and mood outcomes.
Conclusions:
- Cenobamate (CNB) is a safe and effective adjunctive ASM for improving seizure control in PWE.
- CNB did not significantly alter PHQ-9 scores, suggesting a neutral effect on depressive symptoms in this cohort.
- While improved seizure control may influence mood, the variable individual mood impact highlights the need for further research.
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