Use of extended-release and immediate-release anti-seizure medications with a long half-life to improve adherence in epilepsy: A guide for clinicians.

Poor adherence to anti-seizure medications (ASMs) is associated with breakthrough seizures and potentially increased toxicity in patients with epilepsy. Extended-release (ER) drugs and immediate-release (IR) drugs with a long half-life (t1/2) that permit once-daily dosing (such as, perampanel, zonisamide, lamotrigine [IR, ER] and topiramate [ER]) have a number of advantages over short t1/2 ASMs that require multiple daily dosing. These advantages include simplification of dosing regimens, reduction in pill burden, and a decrease in the peak-to-trough fluctuations in serum drug concentration that may be associated with a decreased risk of adverse effects and seizures. Such properties have wider implications in improving patient adherence to treatment. This article is intended as a practical guide for clinicians that provides an overview of the features of ER ASMs and long t1/2 IR ASMs that are advantageous in the context of patient adherence and pharmacokinetic "forgiveness" (after missing a dose). In addition, we note that efforts to improve adherence should not depend solely on drug dosing regimens and drug pharmacokinetics, but should be part of a wider strategy that includes therapeutic drug monitoring, improved healthcare provider-patient dialogue, patient education, and the use of "reminder" technology.

Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (Aged 4-17 Years) With Focal Seizures.

OBJECTIVE: To evaluate the safety and tolerability of adjunctive eslicarbazepine acetate (ESL) in pediatric patients (aged 4-17 years) with refractory focal seizures. METHODS: Pooled safety data from patients aged 4-17 years in Study 208 (NCT01527513) and Study 305 (NCT00988156) were analyzed. Both were randomized, double-blind, placebo-controlled studies of ESL as adjunctive treatment in pediatric patients with refractory focal seizures receiving 1 or 2 antiepileptic drugs. Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs of special interest were evaluated. RESULTS: The safety population comprised 362 patients (placebo, n = 160; ESL, n = 202). The overall incidence of TEAEs was similar between the ESL (67.8%) and placebo groups (65.6%), with no clear dose-response relationship. The most frequently reported TEAEs with ESL were headache, somnolence, vomiting, and diplopia. Overall incidences of SAEs and TEAEs leading to discontinuation were higher with ESL versus placebo (9.9% vs 5.0% and 5.9% vs 2.5%, respectively). The majority of SAEs with ESL occurred in Study 305. Two deaths were reported, 1 with ESL (0.5%) due to cluster seizures (resulting in herniation of the cerebellar tonsils) and 1 with placebo (0.6%) due to asphyxia. TEAEs related to allergic reaction, hyponatremia, hypothyroidism, cytopenia, seizure exacerbation, cognitive dysfunction, psychiatric disorders, or suicide occurred infrequently (<9%). CONCLUSION: Adjunctive ESL was generally well tolerated in children aged 4-17 years with focal seizures. The safety profile of ESL in children was comparable to that observed in adults.

Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures.

OBJECTIVE: The aim of this study was to evaluate long-term effects of adjunctive perampanel on cognition, efficacy, growth, safety, and tolerability in adolescents with inadequately controlled partial seizures. METHODS: Study 235, a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase II study with an open-label extension phase (NCT01161524), was primarily designed to assess the effects of adjunctive perampanel on cognition. Patients (aged ≥12 to <18years) had a diagnosis of epilepsy with inadequately controlled partial seizures, with or without secondary generalization, despite receiving 1-3 antiepileptic drugs. During the double-blind phase, adjunctive perampanel or placebo was administered over a 6-week titration period and a 13-week maintenance period up to 12mg/day. During the extension phase, all patients received perampanel. Data from the extension phase are presented here. Study endpoints included change from baseline in Cognitive Drug Research (CDR) measures of cognition, seizure frequency, growth, development, the occurrence of treatment-emergent adverse events (TEAEs), and laboratory values. RESULTS: A total of 114 patients entered the extension phase (prior double-blind treatment: placebo, n=41; perampanel, n=73). Perampanel had no effect on the CDR system global cognition score, continuity of attention, quality of episodic memory, quality of working memory, or speed of memory but was associated with a significant decline in power of attention at end of treatment compared with baseline (p=0.03). There were no effects on language skills or manual dexterity from baseline to end of treatment. At Weeks 40-52, median reduction in seizure frequency was 74.1%, and 50% responder rate was 66.0%. There were no clinically relevant effects of perampanel on growth or development at end of treatment compared with baseline. Overall, 84.2% of patients experienced at least one TEAE and 70.2% experienced at least one treatment-related TEAE. The most common TEAEs were dizziness (29.8%) and somnolence (19.3%). The TEAEs resulted in the discontinuation of treatment in 6.1% of patients. CONCLUSIONS: In keeping with the 19-week double-blind phase, long-term adjunctive treatment with perampanel did not have any significant overall effects on the CDR system global cognition score in adolescent patients with inadequately controlled partial seizures. Similar trends were observed across the individual CDR system domains. Adjunctive perampanel showed sustained long-term seizure control and had a safety and tolerability profile similar to that observed in prior clinical studies.

Adolescent and caregiver experiences with epilepsy.

Epilepsy during adolescence can impede the development of psychosocial independence and typical biological maturational processes. We examined in parallel the experiences and perceptions of adolescent patients with epilepsy and their caregivers. Specifically, we focused on frequency and type of seizures, comorbid conditions, adherence to therapies, productivity, clinical and quality of life consequences of seizures, estimated use and content of seizure emergency plans, and the patient-physician relationship. Two cross-sectional online surveys were conducted among 153 adolescent patients with epilepsy and their respective caregivers. A total of 35% of adolescents indicated that they had been nonadherent to antiepileptic medications in the prior month. Adolescents scored significantly lower compared with their peers on quality-of-life measures. Adolescents and caregivers reported similarly on nearly all domains. An adolescent-centered epilepsy management program may help alleviate concerns and also help the adolescent independently manage their epilepsy as they transition into adulthood.

Successful treatment of encephalopathy and myoclonus with levetiracetam in a case of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is a devastating progressive degenerative disease of the nervous system presumably caused by a persistent measles virus. Patients commonly present with myoclonia or encephalopathy. There are currently no known curative therapeutic options or effective symptomatic therapy. We treated a 12-year-old boy with subacute sclerosing panencephalitis who presented with acute encephalopathy and myoclonus. Electroencephalogram showed characteristic generalized periodic discharges. Levetiracetam produced dramatic improvement in both myoclonus and encephalopathy. The improvement was clear within 4 days. The electroencephalogram pattern showed improvement as well. Levetiracetam is a promising symptomatic therapy in subacute sclerosing panencephalitis for both the myoclonus and the encephalopathy. In this patient, it also appeared to improve the electroencephalographic pattern. We suggest that the generalized periodic discharges associated with the myoclonus contributed to the patient's encephalopathy.

Seizure emergency plans: patient results from a cross-sectional epilepsy survey.

Guidance for seizure emergency plans exists, although their impact and extent of use in patients with epilepsy are undetermined. This study's primary purpose was to measure the estimated use and content of seizure emergency plans. Secondary objectives included measuring: disease severity, quality of life, productivity, and adherence among patients with and without a plan. An online survey was conducted among 408 patients with epilepsy (ages 18-64) who took one or more antiepileptic drugs. Only 30% of patients reported having a plan, which included avoiding injury, notifying a physician, resting/relaxing, and seeking emergency assistance. Those with a plan were more likely to have experienced more seizures in the past year, to have missed school/work, to have incurred injury, to have visited the ER, to have been hospitalized, to fear additional seizures, and to have lost a job. Seizure emergency plans appear to be reserved for adults with more severe disease, but there may be clinical benefits to developing a plan for all adult patients with epilepsy.

Association of non-adherence to antiepileptic drugs and seizures, quality of life, and productivity: survey of patients with epilepsy and physicians.

Non-adherence to epilepsy medications can interfere with treatment and may adversely affect clinical outcomes, although few studies have examined this relationship. This study assessed barriers and drivers to adherence, its impact on quality of life, and the importance of the patient-physician relationship to adherence. Two cross-sectional online surveys were conducted among 408 adult patients with epilepsy and 175 neurologists who treat epilepsy patients. Twenty-nine percent of patients self-reported being non-adherent to antiepileptic medications in the prior month. Non-adherence was found to be associated with reduced seizure control, lowered quality of life, decreased productivity, seizure-related job loss, and seizure-related motor vehicle accidents. Patient-oriented epilepsy treatment programs and clear communication strategies to promote self-management and patients' understanding of epilepsy are essential to maximizing treatment and quality of life outcomes while also minimizing economic costs.