The LAM-SAFE Study: lamotrigine versus carbamazepine or valproic acid in newly diagnosed focal and generalised epilepsies in adolescents and adults.

Objective: To investigate efficacy and safety of lamotrigine (LTG) versus carbamazepine (CBZ) or valproic acid (VPA) in newly diagnosed focal (FE) and idiopathic generalised (GE) epilepsies in adolescents and adults.

Methods: Open-label randomised comparative multicentre 24-week monotherapy trial in newly diagnosed epilepsy patients of >or=12 years of age. Patients with FE were treated with LTG or CBZ, those with GE received LTG or VPA. The primary efficacy variable was the number of seizure-free patients during study weeks 17 and 24.

Results: Two hundred and thirty-nine patients were included. One hundred and seventy-six patients suffered from FE and 63 from GE. In the FE group, 88 patients each were treated with CBZ or LTG. Ninety-four percent of the CBZ patients and 89% of the LTG patients became seizure-free according to an intent-to-treat analysis (not statistically different). The rate of patients discontinuing treatment due to adverse events or a lack of efficacy was 19% with CBZ compared to 9% with LTG (not statistically different). In the GE group, 30 patients received VPA and 33 LTG. During study weeks 17 and 24, 61% of the LTG patients and 84% of the VPA patients had become seizure-free (not statistically significant). The drop-out rate due to lack of efficacy or adverse events was 12% with LTG and 3% with VPA (not statistically different).

Conclusions: This study indicates that the effectiveness of LTG in focal and generalised epilepsy syndromes as initial monotherapy in patients >or=12 years is in the range of standard first-line antiepileptic drugs.