Pharmacotherapy of Focal Epilepsy in Children: A Systematic Review of Approved Agents

Abstract

Background Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation. Objectives This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children. Data sources Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors’ files. Study appraisal and synthesis methods Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria. Outcomes Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data. Results Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partialonset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures. Conclusions and implications of key findings This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug’s efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.

Early and effective treatment of KCNQ2 encephalopathy

“…PHT and CBZ are sodium‐channel blockers with a well‐known mechanism of action . Drugs targeting sodium channels block the movement of sodium ions through the channels during propagation of the action potential and thus block and prevent the development of seizure activity . Seemingly disparate, voltage‐gated sodium channels and KCNQ potassium channels co‐localize and are bound at critical locations of the neuronal membrane .…”

“…18 Drugs targeting sodium channels block the movement of sodium ions through the channels during propagation of the action potential and thus block and prevent the development of seizure activity. 19 Seemingly disparate, voltage-gated sodium channels and KCNQ potassium channels co-localize and are bound at critical locations of the neuronal membrane. 20 The response to sodium-channel blockers in patients with potassiumchannel disorders could be explained by structure-function approaches showing that modulation of one channel may significantly affect the function of the channel complex.…”

Algorithms of mono- and polytherapy in clinical epileptology

“…Анализ международ-ных рекомендаций и ведущих экспертов по лечению эпи-лепсии показал, что ПЭП для стартовой монотерапии фо-кальной эпилепсии (ФЭ) у детей с классом доказательно-сти I является окскарбазепин, с классом III -карбамазе-пин, клобазам*, ламотриджин, фенобарбитал, фенитоин, топирамат [39].…”

“…Из ПЭП для дополнительной терапии ФЭ у детей с классом доказательности I являются леветирацетам, ла-мотриджин, окскарбазепин и топирамат [39,40]. Несмо-тря на эти данные, наиболее частым ПЭП в стартовой монотерапии эпилепсии у детей являются вальпроаты, как препараты широкого спектра действия с низким про-центом аггравации приступов.…”

Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age: A double‐blind, placebo‐controlled, video‐electroencephalographic trial

“…Whereas seizures can often be effectively managed with AEDs in many pediatric patients, 25%‐40% of patients may not be adequately controlled and/or may experience troublesome side effects . Clinical efficacy and safety studies have been completed in infants and younger children (1 month to <4 years of age) with partial or focal onset seizures (FOS) with adjunctive gabapentin, lamotrigine, oxcarbazepine, topiramate, and levetiracetam . Of these, only levetiracetam is approved by regulatory agencies for children 2 years of age and younger .…”