The Stability and Influence of Barriers to Medication Adherence on Seizure Outcomes and Adherence in Children With Epilepsy Over 2 Years

Rachelle R. Ramsey, PHD; Nanhua Zhang, PHD; Avani C. Modi, PHD


J Pediatr Psychol. 2018;43(2):122-132. 

In This Article

Abstract and Introduction


Objective To determine the stability and influence of adherence barriers on medication adherence and seizure control in pediatric epilepsy.

Methods Caregivers of 118 children aged 2–12 years old with epilepsy completed the Pediatric Epilepsy Medication Self-Management Questionnaire at nine time points over 2 years post diagnosis. Electronically monitored antiepileptic drug adherence and seizure outcome data were collected.

Results Hierarchical linear modeling results for overall barriers remained stable over 2 years. Specific item-level barriers were also generally stable over time, with the exception of running out of medication becoming more of a barrier over time. No specific barriers were related to seizure control; however, difficulties swallowing medication, forgetting, and medication refusal were related to electronically monitored adherence over time.

Conclusions Assessing for specific adherence barriers over time may lead to identification of interventions that result in improved adherence and care.


Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures that affects ~1% of youth (Russ, Larson, & Halfon, 2012). Antiepileptic drugs (AEDs) are the primary treatment modality for most patients with epilepsy, and the overall goal of treatment is no seizures, no side effects and best quality of life (Glauser, 2002). Although multiple efficacious AEDs are available to treat children with epilepsy, one-third of children with newly diagnosed epilepsy continue to have seizures despite the use of an AED (Geerts et al., 2010; Holland & Glauser, 2007; Holland, Monahan, Morita, Vartzelis, & Glauser, 2010; Kwan & Brodie, 2000). The precise reason for experiencing continued seizures despite the use of medications is often unknown, but may be because of seizure type, disease etiology, genetics, medication selection/combination, underlying brain abnormalities, or AED nonadherence (Berg, Testa, & Levy, 2011; Geerts et al., 2012; Glauser et al., 2006; Modi, Ingerski, Rausch, & Glauser, 2011; Modi, Rausch, & Glauser, 2014).

AED nonadherence is both a common and modifiable factor contributing to continued seizures. Prior studies have shown that 58% of young children with epilepsy exhibit nonadherence to AEDs in the first 6 months of treatment (Modi, Rausch, & Glauser, 2011). Although patterns of nonadherence vary in course and level (Modi, Rausch, et al., 2011), children with nonadherence in the first 6 months of therapy are 3.24 times more likely to have continued seizures 4 years post diagnosis (Modi, Rausch, et al., 2014). Variable adherence patterns over the first 2 years of AED therapy have also been shown to result in a higher likelihood of having seizures over the same time course (Modi, Wu, Rausch, Peugh, & Glauser, 2014). AED nonadherence also contributes to other significant health and economic ramifications, such as uninformed clinical decision-making (Modi, Wu, Guilfoyle, & Glauser, 2012), increased health-care costs (Faught, Duh, Weiner, Guerin, & Cunnington, 2008; Faught, Weiner, Guerin, Cunnington, & Duh, 2009), and higher incidence of emergency room visits, hospitalization admissions, motor vehicle injuries, and fractures (Faught et al., 2009).

Given the modifiable nature and significant medical and economic ramifications of nonadherence to AEDs, adherence and barriers to adherence are ideal target areas for interventions aimed to improve the health outcomes of children with epilepsy. Following a prescribed medication treatment of daily oral AED medications can be difficult for families for a variety of reasons and understanding the family's perceptions of their own adherence barriers can aid in intervention selection and development. A recent systematic review indicated that adherence barriers generalize across chronic conditions and are often categorized as follows: relational barriers (peers, parents, health professionals), developmental barriers (strive for normality, freedom vs. control), health and illness barriers (mental well-being, physical well-being including ingestion difficulty, treatment perceptions), forgetfulness, poor organization, medicine complexity, and financial costs (Hanghoj & Boisen, 2014). The quantity and types of barriers endorsed have been found to be associated with nonadherence in children with epilepsy (Modi, Monahan, Daniels, & Glauser, 2010) as well as children with other chronic conditions (Bond, Aiken, & Somerville, 1992; Modi et al., 2010; Simons, McCormick, Devine, & Blount, 2010; Zelikovsky, Schast, Palmer, & Meyers, 2008).

Although lacking in epilepsy, several studies have examined the presence, stability, and influence of barriers in adolescents following a solid organ transplant (Lee et al., 2014; Simons & Blount, 2007; Simons et al., 2010). Specifically, these studies demonstrated temporal stability in the total number of barriers over 18 months and that increased barriers related to Regimen Adaptation and Cognitive Issues (Parent Medication Barriers Scale) were related to poorer adherence for teens following transplant (Simons et al., 2010). In addition, perceived barriers related to child ingestion difficulties were associated with clinical outcomes such as medical complications and mortality (Simons et al., 2010). The stability of barriers to medication adherence at the specific barrier (or item) level over 18 months has also been documented for children taking immunosuppressant medication following a transplant (Lee et al., 2014). In other words, once a child or family endorses a specific barrier, it is likely to be a continued barrier without targeted intervention (Lee et al., 2014). Little evidence is available regarding the presence, stability, and influence of barriers in children with epilepsy.

The purpose of this study was to understand the stability of treatment barriers and the influence of these barriers on adherence and seizure control over time. The current study is modeled after the transplant literature examining the relationship between barriers and distal health outcomes to address these important gaps in the literature by examining specific parent-reported barriers to medication adherence every 3 months over a 2-year period. Our overarching goal was to identify "critical barriers" most associated with health outcomes and adherence that can be targeted for future adherence promotion interventions. It is hypothesized that, similar to barriers experienced by children posttransplant, the overall level of barriers and individual barriers will remain stable over a 2-year period and that barriers will negatively impact adherence and seizure control. Specifically, based on the work Lee and colleagues (2014) and Simons and colleagues (2010), we hypothesized that the following specific barriers would be stable and related to adherence and seizure control: forgetting to give medications, medications are difficult to swallow, activities interfere with taking medications, and child refused to take medication. Although we hypothesized that a linear model would demonstrate the best fit, we will also examine cubic and quadratic models because the stability barriers and the relationship of barriers with adherence and seizure control have not been specifically examined in children with epilepsy.