Original Articles
Efficacy, tolerability, and kinetics of lamotrigine in infants,☆☆

https://doi.org/10.1067/mpd.2002.125256Get rights and content

Abstract

Objectives: To investigate the efficacy, tolerability, and kinetics of lamotrigine 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)

Section snippets

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 benzodiaepines; for partial seizures, previous first-line antiepileptic drugs [AEDs] included phenobarbital, phenytoin,

Results

The study population consisted of 13 patients with a mean age of 3.66 months at the time of initiation of LTG (range, 2 weeks to 12 months). Five were 2 to 4 weeks and 6 were <2 months old. Each had either partial seizures alone (6), infantile spasms alone (6), or both (1) (Table).

Table. Antiepileptic drug to which lamotrigine was added

Antiepileptic drug(s)*No. of patientsSeizure type
Phenobarbital4Partial seizures
2IS
Valproate2IS
Phenytoin and phenobarbital2Partial seizures
Valproate and

Discussion

Our experience shows that LTG can be effective as an add-on medication in infants with partial seizures or with infantile spasms. Lamotrigine had similar efficacy in children <1 year of age with partial seizures as compared with those 1 to 12 years of age. These findings are consistent with previous observations that antiepileptic drugs that are effective in partial seizures in adults and older children are also effective in young children and infants with partial seizure.5, 6 However, the same

Acknowledgements

We thank the Department of Pediatrics staff, nurses, and house staff, particularly Dr Roula Choueri, Dr Dana Hasbini, and Miss Suzan Natour for their help in performing this study. We thank Glaxo-Wellcome for providing the medication and for the LTG assays.

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Supported by grant URB 114170-48119.

☆☆

Reprint requests: Mohamad Mikati, MD, Department of Pediatrics, Adult and Pediatric Epilepsy Program, American University of Beirut, 850 Third Ave (18th Floor), New York, NY 10022.

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