Abstracts

Rationale: Lamotrigine’s utility (LTG) as adjunctive therapy in primary generalized tonic-clonic (PGTC) seizures has been established. Patients in the key trial were randomized if they had generalized spike and wave (GSW) or a normal EEG (nGSW), but were excluded if they had focal spikes. We sought to determine whether there was an outcome difference between GSE and nGSW groups.Methods: We analyzed data from an international, multicenter, randomized, double-blind, placebo-controlled trial of LTG in patients (>2 years, weighing >13 kg) with PGTC seizures who were on a stable regimen of 1 or 2 AED(s). Patients with >3 PGTC seizures in an 8 week baseline phase were randomized (1:1) to add-on LTG or placebo (PBO). LTG dosing was adjusted depending on background AEDs to adjust for pharmacokinetic differences. . The primary endpoint of the original study was percent change from baseline in average monthly PGTC seizures. Here we compared outcome measures between GSW and nGSW groups.Results: 117 patients were randomized. 58 received LTG and 59 received PBO. Baseline EEG showed GSW in 40 patients (69%) taking LTG and 38 patients (64%) taking PBO, and nGSW in 18 patients (31%) taking LTG and 21 patients (36%) taking PBO. Subjects in all groups had similar age of seizure onset, but there were fewer subjects <13 years old in the nGSW group. Concomitant AED use was similar between all groups. The median monthly seizure frequency ranged from 1.8 to 3 seizures per month in the nGSW group and from 2.5 to 2.6 seizures per month in the GSW group. During the combined treatment escalation and maintenance phases of the study, tthere was a significant median percentage change from baseline in seizure frequency in the GSW (LTG -70.2% vs PBO -28.6%; p=0.009) group but not in the nGSW (LTG -64.0% vs PBO -40.7%; p=0.371) group. Similaarly, the median change in seizure counts per month were significantly decreased in the LTG group for patients with GSW (LTG -1.4 vs PBO -0.6; p=0.002) but not patients with nGSW (LTG -1.0 vs PBO -1.2; p=NS). Treatment-emergent adverse events were similar in the PBO groups, but were increased in the LTG GSE group vs the LTG nGSW group (15% vs 39%, respectively).Conclusions: While the absolute response to LTG was similar between the GSW and nGSW groups, the placebo response rate was higher in the GSW group compared to the nGSW group. This finding raises the possibility of misdiagnosis (e.g. psychogenic seizures) in some nGSW patients. Future studies of treatments for PGTC may be more efficient and more easily interpreted if GSW on a baseline EEG is required for inclusion.