Lamotrigine versus Valproic Acid as First-line Monotherapy in Newly Diagnosed Typical Absence Seizures: An Open-label, Randomized, Parallel-group Study


Address correspondence and reprint requests to Dr. G. Coppola at Clinic of Child Neuropsychiatry, Second University of Naples, Via Pansini, 5, 80131 Naples, Italy. E-mail:


Summary: Purpose: To compare the efficacy of lamotrigine (LTG) and valproic acid (VPA) in newly diagnosed children and adolescents with typical absence seizures.

Methods: A randomized, open-label parallel-group design was used. After undergoing an awake video-EEG recording, which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation, eligible patients were randomized to receive LTG or VPA. LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses, followed by 1.0 mg/kg/day for an additional 2 weeks. Thereafter, doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled, intolerable adverse effects occurred, or a maximum dose of 12 mg/kg/day had been reached. VPA was equally uptitrated according to clinical response, starting at 10 mg/kg and increasing by 5 mg/kg/24 h every 3 days, if required, to a maximum of 30 mg/kg/day in three divided doses. Patients were seen in the clinic every month for ≤12 months.The primary efficacy end point at each visit was seizure freedom, defined as lack of clinically observed seizures since the previous visit and lack of electroclinical seizures during ambulatory 24-h EEG testing and a video-EEG session with hyperventilation.

Results: Thirty-eight children (17 boys, 21 girls), aged from 3 to 13 years (mean, 7.5 years), all newly diagnosed with childhood or juvenile typical absence seizures, were enrolled. After 1 month of treatment, 10 (52.6%) of 19 children taking VPA and one (5.3%) of 19 taking LTG were seizure free (p = 0.004). By the 3-month follow-up, 12 (63.1%) children taking VPA and seven (36.8%) taking LTG were controlled (p = 0.19). After 12 months, 13 children taking VPA (dose range, 20–30 mg/kg/day; mean serum level, 76.8 mg/L; range, 51.4–91 mg/L) and 10 taking LTG (dose range, 2–11 mg/kg/day; mean serum level, 8.1 mg/L; range, 1.1–18 mg/L) were seizure free (p = 0.51). Side effects were mostly mild and transient and were recorded in two (10.6%) children treated with VPA and in six (31.8%) treated with LTG.

Conclusions: Both VPA and LTG can be efficacious against absence seizures, although VPA shows a much faster onset of action, at least in part because of its shorter titration schedule.