Minimising co-medication optimises cenobamate efficacy in drug-resistant epilepsy

A specialised neurology clinic in Seville, Spain, shared their successful efforts to optimise the efficacy of cenobamate in highly refractory focal epilepsy. A rapid and drastic reduction of co-medication in conjunction with an increase in mean cenobamate dose led to very high seizure reduction rates, better tolerability and improved patients’ quality of life.

Simplification of therapy can help improve tolerability and adherence in general, and in drug-resistant epilepsy in particular. The current study, presented by Dr Juan Sanchez-Caro (Advanced Neurology Center, Spain), was triggered by another Spanish study of cenobamate in patients with drug-resistant epilepsy, showing a high response regardless of prior and concomitant medication [1,2]. As 1 of the partaking centres, the Advanced Neurology Center in Seville decided to further describe the results of the participants from their hospital, focusing on the possibility of rapidly reducing co-medications when prescribing cenobamate [2].

The study included 34 participants, 21 reached 12 months of follow-up. Cenobamate titration started at 12.5 mg/day, with an initial target of 200 mg/day and allowing further optimisation. After 3 months (n=32), the mean cenobamate dosage was 208 mg, after 12 months it was 326 mg. Participants could significantly decrease the use of concomitant anti-seizure drugs while on cenobamate: from a mean 3.6 defined daily dose (DDD) at baseline to 1.4 DDD after 12 months (P<0.001). Most of the co-medications were taken above the DDD at baseline, but all dosages were reduced, on average by >60%. Often, participants terminated co-medication altogether. For example, after 12 months, 40% had terminated carbamazepine use and 80% had stopped using lacosamide. The mean number of concomitant anti-seizure drugs decreased from 2.9 at baseline to 1.6 at 12 months (see Figure).

Optimising the use of cenobamate and minimising the use of co-medication had a significant effect on seizure frequency. At baseline, the mean number of seizures was 57.8 per month; this was reduced to 5.6 after 12 months. This amounted to a >50% seizure reduction by 18 participants (85.7%) at 12 months, and seizure freedom was achieved by 7 participants (33.3%). The number needed to treat (NNT) to reach a >75% reduction in seizure rate was 1.4 (1.86 in the intention-to-treat analysis).

Finally, the investigated approach also had a significant effect on adverse events (AEs). At baseline, AEs were frequent and included ataxia (35%), dizziness (53%), and somnolescence (65%), but these decreased significantly at 12 months (ataxia 4%, dizziness 10%, drowsiness 30%). No skin rash was detected.

The authors concluded that introducing rapid co-medication reduction while increasing cenobamate dose may be the necessary approach to optimise its efficacy and tolerability, and to improve the quality-of-life for patients with highly refractory epilepsy.

Figure: Number of concomitant anti-seizure drugs between baseline and month 12 [2]

1. Villanueva V, et al. Epilepsia Open. 2023; May 7. Doi: 10.1002/epi4.12757.
2. Sanchez-Caro J, et al. Co-medication management: key to optimize the efficacy and tolerability of Cenobamate. EAN 2023 Annual Meeting, 1-4 July, Budapest, Hungary.

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Posted on 7 September, 20237 September, 2023