Topiramate Monotherapy in Newly Diagnosed Epilepsy in Children and Adolescents

Abstract

A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (< or = 3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.

The effects of antiepileptic drugs on classroom performance

“…Moreover, the language changes are reversible when the medication is discontinued. However, it should be highlighted that both topiramate and zonisamide have proven to be highly effective antiseizure medications for children (Bourgeois, 2004), and treatment limiting adverse events, such as severe cognitive problems, have been found to range from only 4% to 14% in monotherapy patients, depending upon the dose (Glauser et al, 2007).…”

“…Rather, many of the problems with memory reported with the newer AEDs appear to be related to problems with executive functioning, which will be covered in the following section. Specifically, newer AEDs can have effects on attention, concentration, and working memory (e.g., Glauser et al, 2007;Gomer et al, 2007), thus leading to inefficiencies in memory encoding but not necessarily consolidation (Lee et al, 2003). As such, classroom accommodations designed to address deficits in executive functioning are often sufficient to help with AED-related memory issues.…”

“…Observational studies of children have reported a higher rate of ADHD symptoms in children treated with zonisamide (e.g., Kim et al, 2005), and a large recent examination of monotherapy with topiramate in children reported general cognitive complaints that ranged between rates of 8% at low doses and 20% at higher doses. The complaints primarily involved problems with attention and concentration, and they were more common in younger children (ages 6-11 years) (Glauser et al, 2007).…”

Therapeutic Drug Monitoring of Classical and Newer Anticonvulsants

“…This AED was first approved in 1996 for the adjuvant treatment of partial and general seizures in those aged 2 years and older [130]. It is also indicated for the prophylaxis of migraine headaches in adults, and has gained approval for monotherapy in patients 2 years and older with partial onset or primary generalized toniceclonic seizures [131]. Topiramate is rapidly absorbed within 2e4 hours after oral dosing with a bioavailability of greater than 80% [6].…”

Epilepsy in infancy

“…Randomized controlled class I studies support its use as adjunctive therapy for adults and children with refractory partial and generalized epilepsy 4 and as monotherapy for adults and children older than 2 years with new-onset partial and generalized epilepsy. 6,7 Second, in contrast to those AEDs that traditionally have been prescribed for infants, topiramate by itself does not cause neuronal death in the brains of developing rodents 2 and may have neuroprotective effects against seizureinduced neuronal damage via mechanisms separate from its anticonvulsant effect. 8 Thus, there has been a need for class I clinical trials examining the use of topiramate in infants with epilepsy.…”