Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures.

Objective: In patients who do not achieve seizure freedom on low-dose first-line monotherapy antiepileptic drug (AED), the current practice is to increase the AED to higher doses. For patients who fail low dose levetiracetam (LEV), a reasonable alternative to increasing dosage may be the addition of a low-dose adjunctive AED.

Methods: In this open-label, pilot trial, low-dose lacosamide (200 mg/d) was added to adult patients with breakthrough seizures on low-dose monotherapy LEV (≤1500 mg/d). Comparison was made with a retrospective historical control cohort in whom the dose of LEV was raised after a breakthrough seizure. The main objectives were to determine efficacy effect size and tolerability.

Results: Twenty patients were recruited in the prospective polytherapy cohort, of whom 19 received at least 1 dose of adjunctive AED; the monotherapy cohort consisted of 36 patients. Six-month seizure freedom was achieved in 9 of 19 patients in the polytherapy cohort and in 15 of 36 patients in the monotherapy cohort (hazard ratio for seizure occurrence for polytherapy relative to monotherapy was 0.76; 95% confidence interval, 0.35-1.65; P = 0.49). There were treatment emergent adverse effects in 11 patients (61.1%) in the polytherapy cohort and 26 (72.2%) in the monotherapy cohort. Greater number of patients in the monotherapy cohort experienced irritability/depression (33.3% vs 5.6%, P < 0.05).

Conclusions: Low-dose polytherapy with LEV and lacosamide was well tolerated and efficacious. Further studies are needed to determine whether this is a reasonable alternative to high-dose LEV monotherapy.