Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study

This study aimed to determine the efficacy and clinical factors related to the pharmacodynamics of single or combination therapies of valproic acid (VPA), carbamazepine (CBZ), and oxcarbazepine (OXC), three commonly used anti-epileptic drugs (AEDs) in China. The study evaluated the records of 2027 outpatients in a Changsha hospital, located in China, from December 23, 2015 to October 28, 2019. The baseline seizure frequency was assessed during the first visit. AED efficacy was determined based on the reduction in seizures from baseline at the subsequent visits. Multivariable ordinal regression analysis was used to determine the association between the clinical factors (demographic characteristics, clinical features, and medication situation) and AED efficacy. For validation, the clinical efficacies of AEDs were compared as both single agents and in combinations. Differences in adverse effect (AEs) categories were analyzed by Chi-square between AED groups. Records of patients receiving VPA, CBZ, and OXC were evaluated. Serum concentrations of VPA and CBZ is significantly correlated with efficacy (OR 1.030 [1.024-1.037], < 0 0.0001; OR 1.250 [1.146-1.63], < 0.0001, respectively) and OXC efficacy correlated to the serum concentration of the metabolite 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD) serum concentrations (OR 1.060 [1.031-1.089], < 0.0001). Significant differences existed between females and males in VPA efficacy (OR 1.318 [1.033-1.682], = 0.027). After validation, VPA, in combination with OXC (OR 1.93 [1.38-2.70],