Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label,randomized, parallel-group study

Abstract

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. KeyWords: Lamotrigine—Valproic acid—Typical absences— Monotherapy. Valproic acid (VPA) and ethosuximide (ESM) have been shown to be equally effective as monotherapy for typical absence seizures (1,2), and, at present, they are generally considered first-choice drugs for this seizure type. VPA controls absences in∼75% of patients, in addition to being effective against generalized tonic–clonic seizures (70%) and myoclonic seizures (75%). However, its use may involve safety risks for postmenarchal women (3). ESM produces complete control of absences in 70% of treated patients (4,5), but it is unsuitable as monotherapy Accepted Ma