SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1500475
Effectiveness and Safety of Single Anti-Seizure Medication as Adjunctive Therapy for Drug-Resistant Focal Epilepsy based on Network Meta-Analysis
Provisionally accepted
Nian-Jia Deng
Zhixin ZhangChen-Yang Xian-YuYu-Ting TaoYu-Tong MaHui-Jun Li
Teng-Yu Gao
Xin LiuJie Luo
Chao Zhang*- Taihe Hospital, Hubei University of Medicine, Shiyan, China
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Objective: To evaluated the effectiveness and safety of single anti-seizure medication (ASM) when used as adjunctive therapy for drug-resistant focal epilepsy.Methods: We conducted a comprehensive search of PubMed, EMbase, and the Cochrane Library from their inception until February 12, 2025, to identify randomized controlled trials (RCTs) meeting our criteria. The trials were analyzed for their use of ASMs in treating drug-resistant focal epilepsy. Inclusion criteria comprised: 1) Participants aged 12 years or older with drug-resistant focal epilepsy; 2) Incorporation of an additional single ASM as an adjunct to the existing antiepileptic treatment regimen; 3) Comparison with placebo or continuation of the original antiepileptic regimen without a new ASM; 4) Primary outcome as a 50% response rate, with safety as a secondary outcome, encompassing dizziness, somnolence, headache, ataxia, diplopia, fatigue, and nausea; and 5) Study design limited to RCTs. The surface under the cumulative ranking curve (SUCRA) was employed to rank the effectiveness and safety of the ASMs.Results: A total of 53 RCTs involving 17 ASMs as adjunctive therapy and placebo were analyzed. Compared to placebo, the following ASMs demonstrated statistically significant effectiveness in achieving a 50% response rate: brivaracetam (RR=2.07, 95%CI:1.53–2.81), cenobamate (RR=2.12, 95%CI:1.56–2.88), eslicarbazepine acetate (RR=1.95, 95%CI:1.41–2.70), gabapentin (RR=2.30, 95%CI:1.76–3.02), lacosamide (RR=2.22, 95%CI:1.47–3.35), lamotrigine (RR=1.55, 95%CI:1.00–2.40), levetiracetam (RR=2.43, 95%CI:1.88–3.15), oxcarbazepine (RR=3.03, 95%CI:2.08–4.40), perampanel (RR=1.72, 95%CI:1.21–2.44), pregabalin (RR=2.06, 95%CI:1.70–2.50), rufinamide (RR=2.28, 95%CI:1.20–4.31), tiagabine (RR=4.07, 95%CI:2.03–8.18), topiramate (RR=3.10, 95%CI:2.44–3.95), vigabatrin (RR=2.34, 95%CI:1.58–3.46), and zonisamide (RR=2.40, 95%CI:1.76–3.27). Based on SUCRA rankings, tiagabine (92.7%) exhibited the most favorable therapeutic outcome, followed by topiramate (87.3%), oxcarbazepine (83%), and levetiracetam (62.8%). The ASMs with the least favorable therapeutic effects were placebo (1.1%), lamotrigine (17.8%), and perampanel (24.7%).Conclusion: The network meta-analysis revealed topiramate, tiagabine, oxcarbazepine, and levetiracetam as the four most effective adjuvant ASM treatments for drug-resistant focal epilepsy. However, it is noteworthy that topiramate and oxcarbazepine were associated with a higher incidence of somnolence. Additionally, comprehensive safety data for tiagabine and levetiracetam are lacking, necessitating further research. Larger studies are required to solidify these findings and better understand the safety profiles of all involved ASMs.
Keywords: Drug-resistant focal seizures, Anti-seizure medication, Topiramate, levetiracetam, gabapentin, pregabalin
Received: 23 Sep 2024; Accepted: 14 Apr 2025.
Copyright: © 2025 Deng, Zhang, Xian-Yu, Tao, Ma, Li, Gao, Liu, Luo and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chao Zhang, Taihe Hospital, Hubei University of Medicine, Shiyan, China
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