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Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months

From Vanderbilt University, Nashville, TN (J.E.P.-G.); The Children’s Hospital of Denver, Denver, CO (P.L.); Gazi University, Ankara, Turkey (K.G.); American University Medical Center, Beirut, Lebanon (M.A.M.); and Neuroscience Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC (C.R.W., H.S.C., J.M.).

Address correspondence and reprint requests to Dr. Jesús Eric Piña-Garza, Children’s Hospital at Vanderbilt, 11210 Doctor’s Office Tower, 2200 Children’s Way, Nashville, TN 37232-9559 eric.pina-garza{at}Vanderbilt.edu

Objective: This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months.

Methods: The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non–enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained.

Results: The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided ² test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a 50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a 25% reduction) but not those randomly assigned to placebo (5% with a 25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients.

Conclusion: Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.

Abbreviations: AED = antiepileptic drug; EKG = electrocardiogram; NA = not applicable; QTc = corrected QT.

Editorial, page 2093

e-Pub ahead of print on December 12, 2007, at www.neurology.org.

Disclosure: GlaxoSmithKline funded the study. H.S.C. and J.M. are employees of GlaxoSmithKline. C.R.W. was an employee of GlaxoSmithKline during the time the study was conducted and the manuscript was prepared. These authors and other employees of GlaxoSmithKline, in collaboration with independent investigators, participated in the design and conduct of the study; collection, management, analysis, and interpretation of data; and preparation, review, and approval of the manuscript. M.A.M. has received grants (>$10,000) from GlaxoSmithKline for research or activities not reported in this article. J.M. has an equity or ownership interest in the study sponsor that exceeds $10,000. J.E.P.-G. received honoraria (>$10,000) from GlaxoSmithKline during the course of the study. Jane Saiers, PhD, a professional medical writer, assisted with writing the manuscript. GlaxoSmithKline funded Dr. Saiers’ work.

Received December 18, 2006. Accepted in final form August 3, 2007.

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