Elsevier

Pediatric Neurology

Volume 44, Issue 6, June 2011, Pages 414-419
Pediatric Neurology

Original Article
Experience With Lacosamide in a Series of Children With Drug-Resistant Focal Epilepsy

https://doi.org/10.1016/j.pediatrneurol.2010.12.003Get rights and content

We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n = 3), vagus nerve stimulation (n = 9), and ketogenic diet (n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.

Introduction

Lacosamide is a new antiepileptic drug (AED) approved by the US Food and Drug Administration for adjunctive therapy in focal epilepsy in patients more than 17 years old [1]. Because of its novel mode of action of selective enhancement of the slow inactivation of voltage-gated sodium channels [2], [3], it may be specifically helpful in patients who have not responded to other AEDs. There have been 1 phase II [4] and 2 phase III clinical trials with lacosamide [5], [6] that demonstrated good efficacy and tolerability for treatment of focal epilepsy in subjects more than 16 years old. Some reports also provided additional indications in status epilepticus [7], [8], with controlled studies revealing a similar safety and tolerability profile of the intravenous formulation to oral lacosamide [9], [10].

Lacosamide has been demonstrated to have a fast onset of anticonvulsant activity and to greatly reduce focal seizures at doses of 200 to 400 mg daily as adjunct therapy in drug-resistant focal epilepsy in adults [4], [5], [6], [11]. The most common adverse effect was dizziness, which was dose related and observed more in the titration period. Other effects included coordination abnormalities, vomiting, diplopia, nausea, vertigo, and blurred vision [4], [5], [6], [11]. Baseline electrocardiogram was necessary because of selective dose-dependent reversible enhancement of slow inactivation of cardiac sodium channels inducing dose-dependent prolongation of the PR interval [2], [3], [12].

We report the experience with the use of oral lacosamide in children with drug-resistant focal epilepsy at a tertiary-care center, Children’s Hospital Boston.

Section snippets

Patients and Methods

We performed a 2-year retrospective analysis (July 2008 to June 2010) of the electronic charts of the neurology outpatient and inpatient database and reviewed clinical presentation as well as outcome of children receiving lacosamide. The inclusion criteria were use of lacosamide, age up to 21 years, focal epilepsy, and assessment in the Department of Neurology, Children’s Hospital Boston. The exclusion criterion was lack of follow-up visit.

Epileptic seizures were classified according to the

Results

We identified 24 patients who received oral lacosamide. Eight patients were excluded from analysis (3 older than 21 years, 4 with inadequate clinical information, and 1 with primary generalized epilepsy).

Summary

This retrospective study of 16 children (mean age 14.9 years) with drug-resistant focal epilepsy revealed adjunctive lacosamide administration to have good efficacy (median seizure reduction of 39.6% and 37.5% [6/16] with ≥50% seizure reduction) without severe adverse events; 25% (4/16) had unacceptable adverse events, including a patient who manifested depression and suicidal ideation.

Previous Studies

Previous studies have reported lacosamide use in patients more than 16 years old. The median age of our

Conclusion

In this series of 16 children with treatment drug-resistant focal epilepsy and with a mean age of 14.9 years (range 8-21 years) and a median follow-up of 4 months, lacosamide administration led to a median seizure reduction of 39.6%, with 37.5% of the patients demonstrating a ≥50% reduction in seizure frequency and no severe adverse events observed. A prospective multicenter study in children is needed to validate our observations.

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