Effects of Valproate and Carbamazepine Monotherapy on Leukocyte Subsets and Neutrophil-Lymphocyte Ratio in Children

ABSTRACT
Objective: Although the adverse effects of anti-seizure medications (ASMs), like leukopenia and neutropenia, are widely recognized, little is known about how they affect leukocyte subsets. Changes in leukocyte subsets are also used to assess the inflammation status during diseases. The neutrophil-to-lymphocyte ratio (NLR) is widely used for this purpose. This study aims to evaluate the effects of valproate (VPA) and carbamazepine (CBZ) monotherapy on leukocyte subsets and NLR and to determine the relationship of these effects with serum drug levels.
Material and Methods: The data of children with idiopathic epilepsy who began CBZ (n=25) or VPA monotherapy (n=62) and underwent complete blood count examinations before treatment and at 1–6 months (T1) and 9–18 months (T2) after treatment, with at least one concurrent serum ASM level, were collected retrospectively. The data included the number and percentages of leukocytes, neutrophils, lymphocytes, and monocytes, as well as simultaneously measured serum ASM levels. The relationships between serum ASM levels and variables were evaluated with 130 simultaneous measurements in the VPA and 30 in the CBZ groups.
Results: In the VPA group, when compared to baseline, neutrophil count and NLR decreased (p=0.026, p=0.038, respectively), and lymphocyte and monocyte percentages increased (p=0.015, p<0.001, respectively). There were no significant changes in the CBZ group. Serum VPA levels were positively correlated with monocyte counts (r=0.2, p=0.022). Serum CBZ levels were negatively correlated with neutrophil counts (r= -0.574, p=0.001) and NLR (r= -0.413, p=0.023).
Conclusion: VPA monotherapy significantly decreased NLR, supporting its anti-inflammatory effects. The negative correlation of serum CBZ levels with NLR suggested that CBZ may have a dose-related effect on NLR. Consideration of these results may be beneficial in choosing an appropriate ASM for patients with epilepsy.
Keywords: Carbamazepine, leukocyte subsets, neutrophil-lymphocyte ratio, valproate