Abstracts

Rationale: Data on weight changes associated with the use of cenobamate in patients with epilepsy is scarce. In this case series, we have identified 4 patients at 2 institutions with who were prescribed cenobamate, often leading to a robust treatment response who subsequently developed significant unintentional weight loss. We then evaluated all patients who were exposed to cenobamate at the Brigham and Women’s Hospital (BWH) to systematically assess change in weight.


Methods: The initial 4 patients (ages 22-65, 3 males) were individually identified at the epilepsy clinics of the Hartford Hospital and the BWH. The records of all patients exposed to cenobamate at the BWH between its introduction in February 2020 until March 2024 were obtained through the Research Patient Data Registry search. Weight was assessed as the highest dose prior to initiation of medication to the trough weight during medication exposure prior to any dose reduction. The % of weight reduction, dose, and concomitant medications were recorded. Weight loss was not attributed to cenobamate if there was an alternate explanatory etiology. A similar analysis was performed to assess for weight gain.


Results: Dosing of the 4 index patients was between 200-350. The amount of weight loss ranged from 10.3% to 29.2%. Three patients attributed the weight loss to nausea and poor appetite. Weight stabilized after decreasing the dose in all patients. In the patient with the 29.2% weight loss, a reduction in dose from 200 to 150mg resulted in partial weight gain (Figure).

A total of 191 patients obtained at least one dose of cenobamate during the study period at the BWH, of which 19 patients were recorded as having experienced at least a 10% weight loss during cenobamate exposure. Alternate explanations included concurrent C. diff colitis, pneumonia, craniotomy, cancer (4), Of the remaining 12 patients, there were 7 males, median age was 41.5 (IQR 36.3-53.3). The median weight loss was 19.2% (IQR 10.8-29.2%). Median dose was 250mg (IQR 200-300mg); 10 of 12 patients had doses of 200mg or greater. There was no significant correlation between maximum dose and degree of weight change (ρ=0.18, p=NS), but in 4 patients who underwent dose reduction or discontinuation due to weight loss, no further decrease was seen. Patients were on a median of 2 other antiseizure medications; the most common concurrent medications at the time of last follow-up or at time of discontinuation of cenobamate were brivaracetam, lacosamide, and valproic acid, with 3 patients on each of those medications.


Conclusions: While cenobamate is generally thought of as a weight neutral ASM, we have identified 4 patients in 2 centers with serious unintentional weight loss associated with its use despite moderate doses. A comprehensive review at one center reveals that 12 out of 191 patients experienced weight loss of greater than 10% attributable to cenobamate, with most patients at a dose of at least 200mg. In our cohort, the effect was reversible with minor dose reduction. When faced with unusual disproportional weight loss, clinicians should attempt to rule out sinister etiologies first while considering a trial of cenobamate dose reduction.


Funding: None