Practical Use of Newer Antiepileptic Drugs as Adjunctive Therapy in Focal Epilepsy

Abstract

This article lays the background for, and discusses the practical issues surrounding, the adjunctive use of the last four antiepileptic drugs (AEDs) to be licensed for the treatment of pharmacoresistant focal seizures in the UK and elsewhere. More than 30% of adolescent and adult patients will not be fully controlled on the currently available therapeutic armamentarium. After not responding to their first three AED schedules, only a handful of patients attained seizure freedom on subsequent regimens. To optimise the response to any new AED in this setting, it is often necessary to reduce the existing drug burden. The pharmacology, tolerability and safety, and everyday use of lacosamide, eslicarbazepine acetate, retigabine (ezogabine) and perampanel will be reviewed and discussed. This will be accompanied by data from prospective audits with each drug undertaken at the Western Infirmary in Glasgow, Scotland, and a report of their successful introduction in an illustrative case. Overall, there is a large variation in the course of refractory epilepsy and the effect of AED therapy on this process seems minimal. Nevertheless, a number of patients will benefit from the introduction of each new AED, with some becoming seizure-free.

Budget Impact Analysis of Brivaracetam Adjunctive Therapy for Partial-Onset Epileptic Seizures in Valencia Community, Spain

“…Anti-epileptic treatment centres on the greatest reduction of the number of epileptic seizures, while minimising adverse effects and long-term toxicity as far as possible. Clinical evidence shows that monotherapy with anti-epileptic drugs (AEDs) is effective in 70% of patients [5]. The remaining 30% need adjunctive treatment to control the seizures [6] and, of these, approximately 25% have epilepsy that is difficult to control, refractory or resistant to AEDs.…”

“…The neurologist has more than 20 AEDs available for the treatment of epilepsy, some of which have numerous side effects and interactions that can complicate patient treatment and management, especially for those with refractory epilepsy [5]. Since 1993, more than 12 new AEDs have been approved that have an effect on seizure control and a better tolerability profile, as well as a lower risk of drug interactions.…”

The Use of Clobazam as Add-on Treatment in Resistant Epilepsy: Our Retrospective Clinical Data

“…Although most drugs provide seizure control in polytherapy, treatment is discontinued because it is not tolerated due to drug-drug interactions, toxicity, systemic adverse effects, even if it is effective. In the literature, the success of treatment with monotherapy in the refractory epilepsy group was 49.5%, seizure-free status was achieved in 13.3% of patients in the second add-on treatment, and this success decreased to 3.3% with the addition of a third antiepileptic drug (9). In the refractory epilepsy group, it was observed that the success rate was low with add-on treatment in patient groups in which seizure control was not achieved with the first drug (4,9).…”

Perampanel in the treatment of patients with epilepsy

“…У 1 пациента на фоне приема ПЕР были зафиксированы суицидальные мысли [29]. По данным ретроспективного анализа психических и поведенческих побочных эффектов, на фоне приема ПЕР нередко отмечались гнев, агрессия и враждебное поведение, особенно при приеме высоких доз препарата [30][31][32], в основном это касалось подростков [32].…”

“…Так как доза 4 мг/сут одновременно является начальной эффективной, обычно рекомендуют относительно быстрый подъем дозы ПЕР до 4 мг/сут, после чего дальнейшая титрация проводится более осторожно. В случае же развития побочных эффектов при наличии хорошей эффективности возможно разделить дозу на два приема [30]. Что касается раздражительности и агрессии, описанных на фоне приема ПЕР, то, в отличие от таковых на фоне приема леветирацетама, данные нежелательные явления обычно развиваются в самом начале приема ПЕР, а не с увеличением его дозы, хотя также являются дозозависимыми.…”