Abstract
Objective: 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. Methods: 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. Results: 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], p < 0 0.0001; OR 1.250 [1.146–1.63], p < 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], p < 0.0001). Significant differences existed between females and males in VPA efficacy (OR 1.318 [1.033–1.682], p = 0.027). After validation, VPA, in combination with OXC (OR 1.93 [1.38–2.70], p<0.001), or with VGB (Vigabatrin) (OR 2.36 [1.38–2.70], p = 0.002), showed significantly better efficacy than as a single agent. OXC efficacy was also affected by the duration of epilepsy (OR 0.965 [0.946–0.984], p < 0.001). Additionally, the efficacies of OXC and VPA were also affected by the seizure type. Seizure reduction improved significantly with an increasing number of pharmacists’ educations in the first three visits period. There were no differences in AEs incidence among these 3 AEDs except for Psychiatric (0.02) and nervous system disorders (0.0001). Conclusion: Serum concentrations of VPA and CBZ may positively affect their efficacies, while OXC efficacies are correlated to MHD serum concentrations. The efficacy of VPA was higher in females compared to males. VPA-OXC and VPA-VGB combinations had higher efficacies compared to monotherapy. Besides, OXC efficacy is probably reducing by the duration of epilepsy. Additionally, VPA efficacy for focal or generalized seizures is superior to mixed-type seizures. OXC was more effective for focal seizures compared to mixed-type ones. Education provided by pharmacists improved the seizures to some extent, and there were no significant differences between most categories of adverse effects for the investigated AEDs.
Highlights
Epilepsy is one of the most common chronic neurological disorders, requiring continuous attention
Mann-Whitney U test was used to analyze the differences for validation of efficacies of monotherapy of Valproic acid (VPA), CBZ and OXC and with the combination of one specific kind of drug respectively and the polytherapy
We found that seizures decreased significantly after the patients’ first to the third visit to the outpatient services, suggesting that the education provided by the pharmacists and the individual adjustment of anti-epileptic drugs (AEDs) dosage by the clinicians help in improve the treatment outcomes (Ma et al, 2019)
Summary
Epilepsy is one of the most common chronic neurological disorders, requiring continuous attention. Accounting for 1% of the world disease burden (Kwon et al, 2011), it has been ranked as the second most burdensome neurological disorder worldwide in terms of disability-adjusted life years (Murray et al, 2012). PWE often requires life-long AED treatment (Chen et al, 2018). Unpredicted seizures, indeterminable efficacy of AEDs, and their unexpected adverse effects (AEs) can markedly affect the patient’s quality of life. The factors that influence the efficacy of AEDs and their related AEs have not been fully understood. While the pharmacokinetics of AEDs is well understood, further studies are needed to determine the factors related to their efficacy. Investigating the parameters that influence the therapeutic effects and AEs of AEDs may be beneficial in improving the clinical management of epilepsy, including drug selection and replacement
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