Elsevier

Epilepsy & Behavior

Volume 98, Part A, September 2019, Pages 14-18
Epilepsy & Behavior

Pharmacist impact on adherence of valproic acid therapy in pediatric patients with epilepsy using active education techniques

https://doi.org/10.1016/j.yebeh.2019.06.003Get rights and content

Highlights

  • Medication adherence is essential to epilepsy management in pediatric patients with epilepsy.

  • Pharmacists have a positive influence on the treatment of epilepsy by increasing patients' medication adherence.

  • Data on the impact of active education by a pharmacist in the population of pediatric patient with epilepsy in China are limited.

  • The study demonstrates the need to establish mandatory patient education by a pharmacist in China.

Abstract

There is limited information on the impact of active education by a pharmacist in the population of pediatric patients with epilepsy (PWE) in China. The objective of this study was to assess the effect of education by pharmacists on medication adherence and percentage of valproic acid (VPA) samples reaching therapeutic reference range in these patients. This study was conducted at two teaching hospitals in Changsha, China. Patients were retrospectively identified from January 2016 to December 2017. Active education by a pharmacist in both oral and written formats was provided at the intervention hospital whereas standard passive pharmacist service (dispensing and answering questions) was provided at the control hospital. Medication adherence was assessed by the simplified medication adherence questionnaire (SMAQ), and serum concentrations of VPA were collected. The correlation between pharmacist education and medication adherence and percentage of VPA samples reaching therapeutic reference range were analyzed. A total of 2165 patients and 4343 serum VPA concentrations were included in the analysis. For the first therapeutic drug monitoring (TDM) measurement, there was no statistical difference between the two hospitals: 41.3% of VPA samples reached therapeutic range at the intervention hospital compared with 45.4% at the control hospital (χ2 = 3.686, P > 0.05). After pharmacist intervention at the intervention hospital, however, there were significant differences in the percentage of therapeutic VPA samples reaching therapeutic range between the first and the second, third, fourth, and fifth TDM measurements (χ2 = 9.756, P < 0.01; χ2 = 22.840, P < 0.01; χ2 = 15.816, P < 0.01; χ2 = 27.613, P < 0.01).

Based on the SMAQ adherence assessment, adherence increased from a minimum of 56.0% to a maximum of 73.9% with stabilization during the last six months of follow-up at the intervention hospital. Both the medication adherence rate and the percentage of VPA samples reaching therapeutic range increased as the result of active education by a pharmacist, suggesting that continuous pharmacist intervention had a positive impact in outpatient pediatric PWE.

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.

Section snippets

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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