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      The efficacy and safety of third-generation antiseizure medications and non-invasive brain stimulation to treat refractory epilepsy: a systematic review and network meta-analysis study

      systematic-review

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          Abstract

          Background

          The new antiseizure medications (ASMs) and non-invasive brain stimulation (NIBS) are controversial in controlling seizures. So, this network meta-analysis aimed to evaluate the efficacy and safety of five third-generation ASMs and two NIBS therapies for the treatment of refractory epilepsy.

          Methods

          We searched PubMed, EMBASE, Cochrane Library and Web of Science databases. Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM), perampanel (PER), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) were selected as additional treatments for refractory epilepsy in randomized controlled studies and other cohort studies. Randomized, double-blind, placebo-controlled, add-on studies that evaluated the efficacy or safety of medication and non-invasive brain stimulation and included patients with seizures were uncontrolled by one or more concomitant ASMs were identified. A random effects model was used to incorporate possible heterogeneity. The primary outcome was the change in seizure frequency from baseline, and secondary outcomes included the proportion of patients with ≥50% reduction in seizure frequency, and the rate of treatment-emergent adverse events.

          Results

          Forty-five studies were analyzed. The five ASMs and two NIBS decreased seizure frequency from baseline compared with placebo. The 50% responder rates of the five antiseizure drugs were significantly higher than that of placebo, and the ASMs were associated with fewer adverse events than placebo ( p < 0.05). The surface under the cumulative ranking analysis revealed that ESL was most effective in decreasing the seizure frequency from baseline, whereas CNB provided the best 50% responder rate. BRV was the best tolerated. No significant publication bias was identified for each outcome index.

          Conclusion

          The five third-generation ASMs were more effective in controlling seizures than placebo, among which CNB, ESL, and LCM were most effective, and BRV exhibited better safety. Although rTMS and tDCS did not reduce seizure frequency as effectively as the five drugs, their safety was confirmed.

          Systematic review registration

          PROSPERO, https://www.crd.york.ac.uk/prospero/ (CRD42023441097).

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          Most cited references84

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments

            Background Lack of appropriate reporting of methodological details has previously been shown to distort risk of bias assessments in randomized controlled trials. The same might be true for observational studies. The goal of this study was to compare the Newcastle-Ottawa Scale (NOS) assessment for risk of bias between reviewers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza. Methods Cohort studies included in the systematic review and published between 2008–2011 were included. The corresponding or first authors completed a survey covering all NOS items. Results were compared with the NOS assessment applied by reviewers of the systematic review. Inter-rater reliability was calculated using kappa (K) statistics. Results Authors of 65/182 (36%) studies completed the survey. The overall NOS score was significantly higher (p < 0.001) in the reviewers’ assessment (median = 6; interquartile range [IQR] 6–6) compared with those by authors (median = 5, IQR 4–6). Inter-rater reliability by item ranged from slight (K = 0.15, 95% confidence interval [CI] = −0.19, 0.48) to poor (K = −0.06, 95% CI = −0.22, 0.10). Reliability for the overall score was poor (K = −0.004, 95% CI = −0.11, 0.11). Conclusions Differences in assessment and low agreement between reviewers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic reviews.
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              Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.

              To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
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                Author and article information

                Contributors
                Role: Role:
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                URI : https://loop.frontiersin.org/people/920070/overviewRole: Role: Role: Role:
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                09 January 2024
                2023
                : 14
                : 1307296
                Affiliations
                [1] 1Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Institute of Neurological Diseases, North Sichuan Medical College , Nanchong, China
                [2] 2Department of Neurology, The First People’s Hospital of Guiyang , Guiyang, China
                Author notes

                Edited by: Luisa Lilia Rocha, National Polytechnic Institute of Mexico (CINVESTAV), Mexico

                Reviewed by: Walter Besio, University of Rhode Island, United States; S. Reza Ebadi, Tehran University of Medical Sciences, Iran

                *Correspondence: Guohui Jiang, neurodoctor@ 123456163.com

                These authors have contributed equally to this work

                Article
                10.3389/fneur.2023.1307296
                10804851
                38264091
                d5877ffb-69b5-460f-afca-decc7015effb
                Copyright © 2024 Yang, Shangguan, Wang, Liu, Shen, Tang and Jiang.

                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) and the copyright owner(s) 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.

                History
                : 05 October 2023
                : 13 December 2023
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 84, Pages: 13, Words: 8140
                Funding
                Funded by: Science Foundation of China
                Award ID: 81971220
                Funded by: Natural Science Foundation of Sichuan Province
                Award ID: 2023NSFSC0622
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by funding from the Science Foundation of China (No. 81971220) and the Natural Science Foundation of Sichuan Province (No. 2023NSFSC0622).
                Categories
                Neurology
                Systematic Review
                Custom metadata
                Epilepsy

                Neurology
                third-generation antiseizure medications,epilepsy,non-invasive brain stimulation,network meta-analysis,refractory epilepsy

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