Abstracts

Rationale: Dosing lamotrigine (LTG) as adjunctive therapy is based on the effect of the concomitant antiepileptic drug (AED) on the metabolism of LTG: induced, inhibited, or neutral. This analysis was conducted to assess the effect of type of concomitant AEDs on the efficacy of once-daily adjunctive therapy with lamotrigine extended-release (LTG-XR) in subjects with intractable partial seizures with or without secondary generalization.Methods: This post hoc analysis utilized data from an international, multicenter, randomized, double-blind, placebo-controlled trial with the once daily formulation LTG-XR. LTG-naive patients (>13 years) with intractable partial seizures, receiving a stable regimen of 1 or 2 AED(s) were enrolled in an 8-week baseline phase. Patients having >8 partial seizures were randomized (1:1) to receive either once-daily LTG-XR (LAMICTAL-XR) or placebo (PBO). The treatment period consisted of Escalation (7 weeks) and Maintenance (12 weeks) phases with dosing based on background AEDs. Patients were categorized as taking an AED regimen with enzyme inducers (induced), enzyme inhibitors (inhibited), or no effect (neutral). The primary endpoint was percent change from baseline in all partial seizures during the entire treatment phase. The Hodges Lehman estimate for median treatment difference (LTG-XR - PBO) and 95% confidence intervals (CI) were also calculated. Results: Of the 236 patients randomized, 102 were taking the induced regimen (LTG-XR: n=59, PBO: n=43), 73 were taking the inhibited regimen (LTG-XR: n=30, PBO: n=43), and 61 were taking the neutral regimen (LTG-XR: n=27, PBO: n=34). Baseline characteristics were similar between all treatment groups. The median percent decrease from Baseline in partial seizures (LTG-XR vs. PBO) was 42% vs. 26% for the induced group, 60% vs. 24% for the inhibited group, and 37% vs. 18% for the neutral group. Median treatment difference (95%CI) were 12% (-2 to 26%) for the induced group, 30% (13 to 56%) for the inhibited group, and 15% (-9 to 36%) for the neutral group.Conclusions: Once daily LTG-XR appears to be efficacious in patients with partial epilepsy regardless of the type of concomitant AEDs taken at baseline.