31 METHODS We investigated patients <1 year of age with intractable seizures (partial seizures or infantile spasms). Inclusion criteria were (1) intractable seizures that persisted despite trials of at least three of the first-line antiepileptic drugs as monotherapy or polytherapy (for infantile spasms, first-line drugs included adrenocorticotropic hormone, vigabatrine, valproate, or benzodi- aepines; for partial seizures, previous first-line antiepileptic drugs [AEDs] included phenobarbital, phenytoin, carbamazepine, or valproate); (2) ab- sence of a reversible underlying meta- bolic or neoplastic pathogenesis; (3) ability to reliably take the medication; (4) ability of care givers to accurately report seizures; (5) informed consent from the parents or guardians; (6) con- firmation of the occurrence of partial seizures and/or, of infantile spasms ei- ther by direct observation, by defini- tively compatible clinical descriptions and electroencephalographic findings, or, in cases in which there was a ques- tion about the nature of the seizures, by videoelectroencephalographic moni- toring. Those patients in whom there was any doubt about the nature of their seizures were not included in the study. In addition, patients whose seizures were so severe that the slow titration schedule of LTG was judged to be in- appropriate for the patient’s condition were not included in the trial. Lamotrigine (LTG) is effective in adults and in children with general- ized and partial seizures. 1-4 There is limited experience in LTG use in the younger age group of 0 to 12 months of age because there are only limited data concerning LTG efficacy, side ef- Efficacy, tolerability, and kinetics of lamotrigine in infants Mohamad A. Mikati, MD, Michel Fayad, MD, Majed Koleilat, MD, Nabil Mounla, MD, Rania Hussein, MPH, Alia Kazma, MPH, and Khalid Yunis, MD From the Department of Pediatrics, Adult and Pediatric Epilepsy Program, American University of Beirut, New York City, New York. Supported by grant URB 114170-48119. Submitted for publication Aug 31, 2001; revision received Feb 26, 2002; accepted Mar 28, 2002. Reprint requests: Mohamad Mikati, MD, Department of Pediatrics, Adult and Pediatric Epilep- sy Program, American University of Beirut, 850 Third Ave (18th Floor), New York, NY 10022. Copyright © 2002, Mosby, Inc. All rights reserved. 0022-3476/2002/$35.00 + 0 9/21/125256 doi:10.1067/mpd.2002.125256 AED Antiepileptic drug LTG Lamotrigine fects, and kinetics in that population. 3 In this study, 13 infants with in- tractable seizures were treated with LTG (as add-on therapy) with the goal of studying the efficacy, side ef- fects, and kinetics of LTG in that age group. Objectives: To investigate the efficacy, tolerability, and kinetics of lamotrig- ine during the first year of life. Study design: We studied 13 infants with intractable seizures; 7 had partial seizures and 7 had infantile spasms (1 had both). Patients received open-label lamotrigine as add-on therapy for 3 months. Seizure frequency, response ratio, and side effects score were determined and compared with the baseline period. Results: The rate of partial seizures per day decreased from 8.57 ± 2.29 to 4.00 ± 2.15 (P = .027) and infantile spasms from 8.71 ± 2.15 to 3.61 ± 2.762 (P = .028). Apparent clearance increased during the first year of life, with a break point at 2 months of age (mean, 0.119 ± 0.021, 0.217 ± 0.094 L/h per kilogram for infants <2 months and those 2 to 12 months old, respectively, P < .001). Twenty-four–hour concentration to time plots of three 3- to 4- week-old neonates showed a half-life of 23.44 ± 3.57 hours. Compared with a group of 17 older children, LTG had similar efficacy (response ratios, –0.68 ± 0.12 and –0.74 ± 0.11, P = .504), and similar adverse effects scores (0.67 ± 0.67 and 0.23 ± 0.166, P = .95). Conclusions: Lamotrigine is a useful and well tolerated drug for partial seizures and infantile spasms in infants <1 year of age. However, lamotrigine has age-dependent kinetics that must be taken into consideration. (J Pediatr 2002;141:31-5)