Pharmacist impact on adherence of valproic acid therapy in pediatric patients with epilepsy using active education techniques
Introduction
Epilepsy is one of the most common neurological disorders in China, with an overall prevalence of 2.89% that disproportionately affects patients 10–19 years old [1]. Antiepileptic drugs (AEDs) are the mainstay treatment for patients with epilepsy (PWE), and patients often require lifelong AED therapy [2]. Currently, there are more than 20 AEDs available, including both older and newer ones [3]. Older AEDs, such as valproic acid (VPA), phenytoin, and carbamazepine continue to be widely used in clinical practice. However, these drugs tend to cause significant adverse effects and drug–drug interactions because of their variable and nonlinear pharmacokinetics and narrow therapeutic index. Adverse effects of AEDs are significant predictors of quality of life in PWE [4]. Therefore, these drugs usually require therapeutic drug monitoring (TDM) for efficacy and toxicity [5]. Therapeutic drug monitoring is helpful for dosing adjustments, and to gauge patient adherence and search for intervention opportunity [6], [7].
Medication adherence is essential to epilepsy management, and pharmacists are in a unique position to positively affect outcomes. Nonadherence in PWE increases the risk of serious clinical events including increased mortality [8] and places a significant financial burden on the healthcare system resulting to recurrent seizure management [9], [10]. Studies have shown that pharmacists have a positive influence on the treatment of epilepsy by increasing patients' medication adherence [11], [12], [13]. A cross-sectional study found that many PWE want their pharmacists to be more involved in disease management, especially by discussing drug interactions (76%) and adverse drug effects (74%) with them [14]. Pharmacists also have an important role in TDM and its interpretation [11].
Most studies on adherence and TDM are for adult PWE. However, pediatric PWE is a special population that deserves attention considering pharmacokinetic differences may play a part in age-related differences in the incidence of adverse effects. We therefore established a medication education and consultation service for pediatric PWE in an outpatient pediatric clinic. The roles of the pharmacists were to (1) monitor drug therapy for efficacy and adverse reactions; (2) provide education to pediatric PWE and patients' caregivers on epilepsy and AEDs to increase patients' medication adherence; and (3) ensure that TDM is performed appropriately based on adherence and dosing history. The aim of this study was to assess the impact of education by a pharmacist on medication adherence in pediatric PWE.
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Patients and study setting
The study population included outpatient pediatric PWE (age: < 14 years) who were treated between January 2016 and December 2017 at two study hospitals: the control hospital (Hunan Children's Hospital) and the intervention hospital (Xiangya Hospital, Central South University). Both hospitals are academic tertiary hospitals located in Changsha, Hunan Province, China. Inclusion criteria were (1) a diagnosis of epilepsy and treated with VPA for more than one month and (2) patients with at least one
Patient characteristics
A total of 2165 patients and 4343 serum VPA concentrations were included in the analysis. From the intervention hospital, there were 1031 patients with 1902 VPA samplings. The average age was 5.0 years, with 62.6% being males. From the control hospital, there were 1134 patients with 2441 VPA samplings. The average age was 4.0 years, with 60.0% being male (Table 1).
Analysis of VPA blood concentration changes with the number of clinic visits
Patients were divided into five groups according to VPA TDM frequencies: 1, 2, 3, 4, and ≥ 5 TDMs. We analyzed differences with
Discussion
To the best of our knowledge, this is the first study in China evaluating pharmacist impact on medication adherence in pediatric PWE on valproate acid therapy using both TDM and SMAQ assessments. The study demonstrates that active patient education by pharmacists not only increases the proportion of patients' medication adherence but also increases the percentage of VPA samples reaching therapeutic range.
Nonadherence rates in the population of pediatric PWE range from 3.5% to 68% depending on
Conclusion
Our study demonstrates that active education by a pharmacist can improve adherence to VPA therapy in pediatric PWE. This improved medication adherence leads to more TDM samples reaching a therapeutic reference range. Ultimately, pharmacist intervention in the pediatric subgroup with epilepsy can positively impact seizure control.
Funding
The study was supported by the National Natural Science Foundation of China [grant number 81373491], and the Key Research and Development Program in Hunan Province [grant number 420010054].
Declaration of Competing Interest
Authors declare that they have no conflicts of interests with respect to the research, authorship, and/or publication of this manuscript.
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