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NEUROLOGY 2007;69:1610-1618
© 2007 American Academy of Neurology

Lamotrigine extended-release as adjunctive therapy for partial seizures

D. K. Naritoku, MD, C. R. Warnock, J. A. Messenheimer, MD, R. Borgohain, DM, S. Evers, MD, A. B. Guekht, MD, V. A. Karlov, MD, B. I. Lee, MD and L. Ríos Pohl, MD

From the Departments of Neurology and Pharmacology (D.K.N.), Southern Illinois University, Springfield; Neuroscience Medicine Development Center (C.R.W., J.A.M.), GlaxoSmithKline, Research Triangle Park, NC; Department of Neurology (R.B.), Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, India; Department of Neurology (S.E.), University of Münster, Germany; The Department of Nervous Diseases (A.B.G.), Russian State Medical University, Moscow; Neurology Diseases Department (V.A.K.), Moscow State Medical-Dentistry University, Russian Federation; Yonsei University Severance Hospital (B.I.L.), Seoul, Korea; and Hospital San Borja Arriarán (L.R.P.), Santiago, Chile.

Address correspondence and reprint requests to Dr. Dean K. Naritoku, Southern Illinois University, PO Box 19637, Springfield, IL 62794-9637 dnaritoku{at}siumed.edu

Objective: To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy.

Methods: Patients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained.

Results: Of the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint—entire 19-week treatment phase: 46.1% vs 24.2%, p = 0.0004 via Wilcoxon test; escalation phase: 28.0% vs 16.3%, p = 0.028; maintenance phase: 58.0% vs 26.7%, p < 0.0001). The percentage of patients with ≥50% reduction in partial seizure frequency (42.2% vs 24.2%, p = 0.0037) and time to ≥50% reduction in partial seizure frequency (p = 0.0007) also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 17%, placebo 15%) and dizziness (lamotrigine XR 18%, placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant.

Conclusions: Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation.

GLOSSARY: AED = antiepileptic drug; AEP = Adverse Experience Profile; CES-D = Center for Epidemiologic Studies-Depression Scale; ESS = Epworth Sleepiness Scale; IR = immediate-release; NDDI-E = Neurological Disorders Depression Inventory-Epilepsy; POMS = Profile of Mood States; QOLIE-31-P = Quality of Life in Epilepsy-31-P; SSQ = Seizure Severity Questionnaire; VNS = vagus nerve stimulators; XR = extended-release.

Disclosure: This study was sponsored and conducted by GlaxoSmithKline Research and Development (GSK R&D). The clinical team (J.A.M. and C.R.W.) from the sponsor led the design and conduct of the study, management, analysis, and interpretation of the data, and preparation, review, and approval of this manuscript in conjunction and consultation with the investigators. All authors had full access to the data. Dr. Naritoku has performed clinical trials for GSK and other pharmaceutical companies. He is also on the speakers bureau for GSK (<$10,000). Clay Warnock and Dr. Messenheimer are full-time employees of GSK R&D. Drs. Borgohain, Evers, Guekht, Karlov, and Pohl have nothing to disclose. Dr. Lee has received grants from GSK R&D for other research activities (<$10,000). GlaxoSmithKline funded the work of Jane Saiers, PhD, who assisted in writing this article.

Received December 15, 2006. Accepted in final form May 7, 2007.






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