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Levetiracetam and Peripheral Oxidative Stress Biomarkers in Epilepsy: A Systematic Review of Human Evidence
Robert Mîndreanu1, Simona Clichici1, Bianca Buleteanu2
1Department of Physiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Abstract:
Oxidative stress is implicated in epilepsy, but seizures, disease severity, diet, comorbidity and treatment all influence circulating redox biomarkers. We systematically reviewed human evidence on levetiracetam (LEV) under three estimands: within-person change, LEV-treated epilepsy versus healthy controls, and LEV versus other antiseizure medications. PubMed/MEDLINE, Cochrane Library, Web of Science and Scopus were searched from inception to 15 July 2026 (PROSPERO CRD420261448016; OSF HXA4U). Eleven non-randomized studies contributed 297 participants-the sum of LEV subgroups with analysable biomarker data, not the total enrolled populations. Effect estimates with 95% confidence intervals were calculated here wherever reporting permitted; none could be derived for four studies, and those derived are wide, inconsistent in direction, or from designs that cannot attribute change to LEV. Meta-analysis was inappropriate: definitions, matrices, assays, estimands and variance reporting were incompatible. Certainty was very low for every outcome-domain/comparator body, and a sensitivity analysis excluding one report failing a post hoc source-verifiability check (10 studies, 265 participants) changed no conclusion. This review's contribution is not an estimate of LEV's redox effect but a demonstration of why the literature cannot establish one: the human evidence is not of sufficient validity to support or refute such an effect.
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