Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

Abstract

Abstract-Objective:To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. Methods: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. Results: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. Conclusions: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Clinical Development of Antiepileptic Drugs for Children

“…In concert with adult trials, trials in refractory seizure types and epilepsy syndromes have the most consistent trial designs and can be expected to continue as part of most pediatric development programs. 16,27 Adaptations for younger children and infants have included shortening the baseline and treatment phases and counting seizures using video-EEG monitoring. New-onset seizures offer more challenges in trial design from both an ethical and practical perspective.…”

“…28 An evolution of trial design may provide for ethical, practical, and interpretable studies but will not overcome the recruitment challenges due to small numbers of children with various seizure types. Thus, multicenter trials will continue to be designed and conducted on a worldwide basis.…”

Treatment of partial seizures with gabapentin: Double‐blind, placebo‐controlled, parallel‐group study*

“…15 In another review, gabapentin is recommended as an adjunctive therapy in refractory epilepsy as well as lamotrigine, tiagabine, topiramate, oxcarbazepine, levetiracetam, zonisamide, and pregabalin. 16 For a comparison of the safety and tolerability of new AED, 1222 patients who were receiving more than 1200 AED regimens were reviewed for the incidence of rash. 17 The incidence was highest for patients receiving phenytoin (9.4%), carbamazepine (6.6%), oxcarbazepine (6.1%), and lamotrigine (5.6%); rates were lowest for patients receiving gabapentin (0.2%) and topiramate (0%).…”

Currently Available Antiepileptic Drugs

“…Recently published AED treatment guidelines from the American Academy of Neurology and the American Epilepsy Society for the use of GBP, LTG, TPM, TGB, OXC, LEV, and ZNS in the treatment of new-onset and medically refractory seizures are based on evidence of efficacy, tolerability, and safety in adults and children. 66,67 However, while clinical practice is ideally evidence-based, there are clinical situations requiring AED selections for which there are few if any relevant clinical studies. 68 For example, there are few head-to-head studies of currently available AEDs as initial therapy for specific seizure types or age groups.…”