Brivaracetam as a substitute for levetiracetam in children with drug-resistant epilepsy and inadequate response to levetiracetam: a single-center retrospective study of 24 cases over 6 months_Journal of Epilepsy

Authors：

LIN Haisheng , YU Shufeng , DAI Jin , PENG Bingwei , ZHU Haixia , LI Xiaojing , WANG Xiuying ,  HU Jun

Department of Neurology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510120, China;

Corresponding?author：

HU Jun, Email: hujun2252@126.com

Keywords：

Children; Drug-resistant epilepsy; Brivaracetam; Levetiracetam; Substitute therapy; Efficacy; Safety

DOI：

10.7507/2096-0247.202603007

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Objective To investigate the efficacy and safety of brivaracetam (BRV) as a substitute therapy for children with drug-resistant epilepsy (DRE) who have exhibited a suboptimal response to levetiracetam (LEV). Methods Twenty-four children aged 3 to 13 years with drug-resistant epilepsy and poor response to LEV were retrospectively included. LEV was replaced with BRV within 3 days at a dose ratio of 10∶1. The maximum maintenance dose of BRV was ≤5 mg·kg^?1·d^?1. Patients were followed up for 6 months. Changes in seizure frequency before treatment and at 1, 3, and 6 months of treatment were observed and analyzed. Treatment-related adverse events and laboratory indicators were also recorded. Results Through self-controlled analysis, after 6 months of treatment, the mean frequency of epileptic seizures in pediatric patients decreased from a baseline of 27.2±42.5 times/28 days to 8.9±14.6 times/28 days. The median frequency of seizures decreased from a baseline of 2 times/28 days to 1 time/28 days. The difference compared to baseline was statistically significant (P=0.002). The clinical response rate was 45.8%, and the complete seizure-free rate was 41.7%, with efficacy showing an increasing trend over the treatment duration. Only 3 cases (12.5%) experienced mild to moderate adverse reactions (1 case each of dizziness, nausea/vomiting, and abdominal pain). Only 1 case discontinued medication due to adverse reactions. Hematology, urinalysis, liver and kidney function, etc., showed no abnormalities, and there were no serious adverse events. Conclusions Substituting LEV with BRV demonstrates significant efficacy in children with DRE who have a suboptimal response to LEV. The regimen is associated with few adverse events and good tolerability, suggesting it is a viable and effective alternative clinical strategy.

Citation： LIN Haisheng, YU Shufeng, DAI Jin, PENG Bingwei, ZHU Haixia, LI Xiaojing, WANG Xiuying, HU Jun. Brivaracetam as a substitute for levetiracetam in children with drug-resistant epilepsy and inadequate response to levetiracetam: a single-center retrospective study of 24 cases over 6 months. Journal of Epilepsy, 2026, 12(4): 275-280. doi: 10.7507/2096-0247.202603007 Copy

1.	Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med, 2000, 342(5): 314-319.
2.	Glauser T, Ben-menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2013, 54(3): 551-563.
3.	Menderes D, Akbas S, Serdaroglu E, et al. Antiseizure medication discontinuation in pediatric epilepsy: Real-world insights. Epilepsy Res, 2026, 221: 107742.
4.	Klein P, Bourikas D. Narrative review of brivaracetam: preclinical profile and clinical benefits in the treatment of patients with epilepsy. Adv Ther, 2024, 41(7): 2682-2699.
5.	Tulli E, Di cara G, Iapadre G, et al. An update on brivaracetam for the treatment of pediatric partial epilepsy. Expert Opin Pharmacother, 2021, 22(11): 1387-1395.
6.	Brandt C, May TW, Bien CG. Brivaracetam as adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy: the current evidence base. Ther Adv Neurol Disord, 2016, 9(6): 474-482.
7.	Lattanzi S, Cagnetti C, Foschi N, et al. Brivaracetam add-on for refractory focal epilepsy A systematic review and meta-analysis. Neurology, 2016, 86(14): 1344-1352.Lattanzi S, Cagnetti C, Foschi N, et al. Brivaracetam add-on for refractory focal epilepsy A systematic review and meta-analysis. Neurology, 2016, 86(14): 1344-1352.
8.	中國抗癲癇協會. 臨床診療指南(癲癇病分冊)(2023修訂版). 北京: 人民衛生出版社, 2015: 1-151.
9.	Naganawa M, Gallezot JD, Finnema SJ, et al. Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A. Ejnmmi Res, 2022, 12(1): 71.
10.	Okada M, Fukuyama K, Shiroyama T, et al. Brivaracetam prevents astroglial L-glutamate release associated with hemichannel through modulation of synaptic vesicle protein. Biomed Pharmacother, 2021, 138: 111462.
11.	Watkins LV, Dunstall H, Musicha C, et al. Rapid switching from levetiracetam to brivaracetam in pharmaco-resistant epilepsy in people with and without intellectual disabilities: a naturalistic case control study. J Neurol, 2023, 121: e5849.
12.	Spilárová Z, Sládková S, Belohlávková A, et al. Brivaracetam use in children with epilepsy: A retrospective multicenter study. Seizure, 2024, 121: 243-252.
13.	Kung Y Y, Kung W M. Brivaracetam in refractory epilepsy: mechanism, tolerability, and clinical positioning. Curr Neuropharmacol, 2026 Mar 27.
14.	Ryvlin P, Dimova S, Elmoufti S, et al. Tolerability and efficacy of adjunctive brivaracetam in adults with focal seizures by concomitant antiseizure medication use: Pooled results from three phase 3 trials. Epilepsia, 2022, 63(8): 2024-2036.
15.	Yamagata A, Ito K, Suzuki T, et al. Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A. Nat Commun, 2024, 15(1): 3027.

1. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med, 2000, 342(5): 314-319.
2. Glauser T, Ben-menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2013, 54(3): 551-563.
3. Menderes D, Akbas S, Serdaroglu E, et al. Antiseizure medication discontinuation in pediatric epilepsy: Real-world insights. Epilepsy Res, 2026, 221: 107742.
4. Klein P, Bourikas D. Narrative review of brivaracetam: preclinical profile and clinical benefits in the treatment of patients with epilepsy. Adv Ther, 2024, 41(7): 2682-2699.
5. Tulli E, Di cara G, Iapadre G, et al. An update on brivaracetam for the treatment of pediatric partial epilepsy. Expert Opin Pharmacother, 2021, 22(11): 1387-1395.
6. Brandt C, May TW, Bien CG. Brivaracetam as adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy: the current evidence base. Ther Adv Neurol Disord, 2016, 9(6): 474-482.
7. Lattanzi S, Cagnetti C, Foschi N, et al. Brivaracetam add-on for refractory focal epilepsy A systematic review and meta-analysis. Neurology, 2016, 86(14): 1344-1352.Lattanzi S, Cagnetti C, Foschi N, et al. Brivaracetam add-on for refractory focal epilepsy A systematic review and meta-analysis. Neurology, 2016, 86(14): 1344-1352.
8. 中國抗癲癇協會. 臨床診療指南(癲癇病分冊)(2023修訂版). 北京: 人民衛生出版社, 2015: 1-151.
9. Naganawa M, Gallezot JD, Finnema SJ, et al. Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A. Ejnmmi Res, 2022, 12(1): 71.
10. Okada M, Fukuyama K, Shiroyama T, et al. Brivaracetam prevents astroglial L-glutamate release associated with hemichannel through modulation of synaptic vesicle protein. Biomed Pharmacother, 2021, 138: 111462.
11. Watkins LV, Dunstall H, Musicha C, et al. Rapid switching from levetiracetam to brivaracetam in pharmaco-resistant epilepsy in people with and without intellectual disabilities: a naturalistic case control study. J Neurol, 2023, 121: e5849.
12. Spilárová Z, Sládková S, Belohlávková A, et al. Brivaracetam use in children with epilepsy: A retrospective multicenter study. Seizure, 2024, 121: 243-252.
13. Kung Y Y, Kung W M. Brivaracetam in refractory epilepsy: mechanism, tolerability, and clinical positioning. Curr Neuropharmacol, 2026 Mar 27.
14. Ryvlin P, Dimova S, Elmoufti S, et al. Tolerability and efficacy of adjunctive brivaracetam in adults with focal seizures by concomitant antiseizure medication use: Pooled results from three phase 3 trials. Epilepsia, 2022, 63(8): 2024-2036.
15. Yamagata A, Ito K, Suzuki T, et al. Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A. Nat Commun, 2024, 15(1): 3027.

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Brivaracetam as a substitute for levetiracetam in children with drug-resistant epilepsy and inadequate response to levetiracetam: a single-center retrospective study of 24 cases over 6 months

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