Abstracts

Rationale: Approximately 38% of patients continue to have seizures despite the availability of numerous anti-seizure drugs (ASDs). Medication nonadherence has been shown to directly contribute to poor seizure control. Unfortunately, there is a lack of emphasis on addressing nonadherence in the clinic. In one study, over half of therapy changes instructed by clinicians were in patients that demonstrated nonadherence prior to a seizures (Epilepsy Behav. 2012;25(4):481-484). This real-world scenario demonstrates how potentially unwarranted alterations to a patient’s drug regimen are made, when improving nonadherence may have resulted in improved seizure control. A majority of therapy changes in this study were dose escalations, which increases the risk of ASD dose-dependent side effects, increases the medication cost, and contributes to misdiagnoses. Additionally, it is unknown what effect a dose escalation, and continued nonadherence, has on seizure control when compared to addressing nonadherence alone. We have used an animal model of acquired epilepsy to model this comparison and study how alterations to pharmacotherapy made without consideration of an individual patient’s poor adherence effects seizure control. Methods: Male Sprague Dawley rats with newly diagnosed epilepsy were treated with carbamazepine (CBZ, 300 mg/kg/day, p.o.) on a 50% nonadherent paradigm for 4 weeks to establish a baseline nonadherent seizure rate. Following the nonadherent baseline period, animals were randomized to one of three-treatment interventions and monitored for six weeks. Groups included no change in therapy: Rats continued on the 50% nonadherent paradigm. Dose escalation: The dose of CBZ was doubled (600 mg/kg/day, p.o.) and the 50% nonadherent paradigm continued. Adherence addressed: Rats continued the initial dose of CBZ but the nonadherence was changed to 100%, i.e. fully adherent. Results: The no change in therapy group had a doubling in seizure burden over the 6-week treatment phase of the study. The dose escalation arm also had worsening of daily seizure burden and only a modest, nonsignificant, improvement in seizure burden compared to no change in therapy. In contrast, the adherence addressed group saw a 40% reduction in daily seizure burden, a significant improvement when compared to the no change in therapy group. It should be noted that both the dose escalation and adherence addressed groups received the same average daily dose (300 mg/kg/day) and therefore the observed difference between these arms can be attributed to their respective adherence paradigms, rather than a dose response. Conclusions: We have found that when medication nonadherence is not addressed there is a worsening of overall daily seizure burden, even if the dose of ASD is increased. In contrast, addressing nonadherence alone results in improved seizure control. The significance of these findings can directly translate to the clinical management of patients with epilepsy and demonstrate that improving nonadherence is value-based intervention that results in lower doses, fewer medications, and better seizure control. Funding: NINDS, NIH Contract HHSN271201100029C