Summary:Purpose: To investigate whether lamotrigine (LTG) monotherapy is effective and safe for newly diagnosed typical absence seizures in children and adolescents (aged 3-15 years, n = 45).Methods: A "responder-enriched" study design was used: open-label dose escalation was followed by placebo-controlled, double-blind testing of LTG. Conventional hyperventilation testing with EEG recording was used to confirm diagnoses and assess treatment success defined as complete freedom from seizures. Ambulatory 24-h EEG recordings provided supporting evidence of effectiveness. Safety was assessed by evaluation of adverse events, vital signs, and physical, neurologic, and laboratory examinations. Plasma samples were taken to evaluate the pharmacokinetics of LTG. Results:During initial open-label dose escalation, 71.4% of patients (intent-to-treat) or 82% (per protocol analysis) became seizure free; individual patients responded at doses ranging from 2 to 15 mg/kg/day (median, 5.0). In the placebocontrolled, double-blind phase of the study, statistically significantly more patients remained seizure free when treated with LTG (62%) than with placebo (21%; p < 0.02; for the intentto-treat analysis). Mean plasma concentrations of LTG, were linearly related to dose, although there was substantial interindividual variation. No patients were withdrawn from the study for any safety-related reason.Conclusions: LTG monotherapy is effective for typical absence seizures in children and is generally well tolerated. Key Words: Lamotrigine-Pediatric-Absence seizuresEfficac y-Tolerability .Typical absence seizures (TASs) account for -13-24% of all epilepsy in children and adolescents (1). The seizures involve brief loss of awareness, responsiveness, and memory, and are accompanied by regular and symmetric 3-Hz spike and slow wave discharges in EEG recordings (2,3). Current therapies for TASs include ethosuximide (ESM) and valproic acid (VPA), both of which are highly effective. However, ESM has little efficacy for other types of seizures, and VPA, especially in children, has been associated with hepatic and hematologic adverse effects, weight gain, hair loss, and tremor.Lamictal (lamotrigine; 6-(2,3-dichloropheny1)-1,2,4-triazine-3,5-diamine) is chemically unrelated to any

A 17-year-old female developed hyperammonemic encephalopathy 2 weeks after valproic acid (VPA), 500 mg twice a day, was added to her regimen of topiramate (TPM), 200 mg twice a day. She presented to the emergency department (ED) with altered mental status, hypotension, bradycardia, and lethargy. Laboratory analysis showed mild non-anion gap hyperchloremic acidosis, serum VPA concentration of 86 mg/L, and urine drug screen result that was positive for marijuana. She was admitted to the pediatric intensive care unit for persistent symptoms, prolonged QTc, and medical history. Blood ammonia concentrations were obtained because of her persistent altered mental status, initially 94 µmol/L and a peak of 252 µmol/L. A serum carnitine profile was obtained at the time of hyperammonemia and was found to be normal (results were available postdischarge). VPA and TPM were discontinued on day 1 and day 2, respectively, as the patient's blood ammonia concentration remained elevated. On day 3, her mental status had returned to baseline, and blood ammonia concentrations trended downward; by day 4 her blood ammonia concentration was 23 µmol/L. VPA has been associated with numerous side effects including hyperammonemia and encephalopathy. Recently, drug interactions with TPM and VPA have been reported; however, serum carnitine concentrations have not been available. We discuss the possible mechanisms that VPA and TPM may affect serum ammonia and carnitine concentrations and the use of levocarnitine for patients or treating toxicity.INDEX TERMS: hyperammonemia, levocarnitine, serum carnitine, topiramate, valproic acid J Pediatr Pharmacol Ther 2013;18(2):128-136

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