Comparative Analysis of Systemic Inflammatory Biomarkers Across Multiple Antiseizure Medications: A Single-Center Retrospective Cohort Study of 1782 Patients

Abstract

Background/Objectives: The aim of this study was to elucidate the associations between the use of various ASMs and systemic anti-inflammatory effects in a single large cohort using routine blood tests. Methods: Patients who underwent blood tests within three months of their first visit to our clinic were included. The systemic inflammatory index (SII, platelet × neutrophil/lymphocyte ratio), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and fibrinogen-albumin ratio (FAR) were compared across specific ASMs. Data from a total of 1782 patients with epilepsy were analyzed. Results: Multiple linear regression analysis revealed that valproate use was significantly associated with lower SII, PLR, and FAR values. Additionally, carbamazepine and oxcarbazepine use were associated with the FAR, whereas topiramate use was associated with the PLR. When a dichotomized category for each inflammatory marker was used, dividing the lowest quartile and the other quartiles, VPA use was significantly associated with all four markers. Topiramate use was associated with lower SII, NLR, and PLR values, and carbamazepine use was associated with lower SII, FAR, and PLR values. Conclusions: These findings highlight the closer association between valproate, compared to other ASMs, and systemic inflammatory responses. These findings may offer valuable insights into the underlying mechanisms of the therapeutic effects of valproate.

Keywords: antiseizure medication; carbamazepine; inflammation markers; topiramate; valproate.

Figure 1

Linear regression-based anti-inflammatory profiles of antiseizure medications (ASMs). Heatmap showing standardized beta coefficients from multiple linear regression analyses, in which systemic inflammatory markers were treated as continuous dependent variables. These results demonstrate the distinct anti-inflammatory effects of commonly used ASMs. * p < 0.05; ** p < 0.01; VPA, valproate; TPM, topiramate; LTG, lamotrigine; CBZ, carbamazepine; LEV, levetiracetam; OXC, oxcarbazepine.

Figure 2

Adjusted levels of systemic inflammatory markers across antiseizure medication groups. Adjusted mean values with standardized errors of the means for each inflammatory marker are shown according to the ASM exposure status. Analyses were based on multiple linear regression, adjusting for potential confounders. (a) Systemic inflammation index (SII), (b) platelet–lymphocyte ratio (PLR), (c) fibrinogen–albumin ratio (FAR), and (d) neutrophil–lymphocyte ratio (NLR).

Figure 3

Forest plots showing the associations between systemic inflammatory indices and clinical parameters, including the antiseizure medications used. Each marker, SII, FAR, NLR, and PLR, was dichotomized into the lowest quartile and the remaining higher quartiles. Odds ratios with 95% confidence intervals are presented, with the lowest quartile used as the reference. Valproate had the lowest odds ratios across multiple markers. Topiramate, carbamazepine, and oxcarbazepine showed selective associations, whereas levetiracetam and lamotrigine generally showed no significant differences.

Figure 4

Overlap of significant associations between ASMs and inflammatory markers according to logistic regression. Venn diagram illustrating the overlap of ASMs significantly associated with dichotomized inflammatory markers, based on binary logistic regression. Valproate was consistently associated with all four markers. Topiramate and carbamazepine were each associated with three markers, whereas oxcarbazepine was associated with one.