Introduction

Drug-resistant epilepsy is reported in almost 30% of patients, which emphasizes on the need to develop novel anti-seizure medications (ASMs). Lacosamide, a functionalized amino acid, is a newer anti-epileptic drug which selectively enhances the slow inactivation of voltage-gated sodium channels and reduces the excitability of pathological neurons. It also acts on the GABA receptor which is helpful in status epilepticus.

Aim

To assess the efficacy and safety of adjunctive lacosamide (LCM) in patients with focal-onset seizures

Patient Profile

• 106 patients (aged ≥16 years) with focal-onset seizures, with or without combined secondarily generalized seizures

Method

Study Design

• Single-center prospective observational study
• Patients received LCM as an add-on treatment; initial dose was 50 mg twice daily and after two weeks, the maintenance dose was 100 mg twice daily

Endpoints

• Efficacy endpoints: Seizure frequency
• Tolerability endpoints: adverse events (AEs), LCM discontinuation and clinical laboratory tests at 3 and 6 months

Results

Efficacy

• Adjunctive lacosamide treatment was associated with an overall response rate of 53.3% at 3 months and 70.4% at 6 months
• It achieved seizure freedom in 19%, seizure frequency reduction of ≥50% in 39%, seizure frequency reduction of <50% in 30.5%, no change in seizure frequency in 10.5%, and worsening in seizure frequency in 1(0.9%) patient at 3 months
• At 6 months, add-on lacosamide treatment achieved seizure freedom in 26.5%, seizure frequency reduction of ≥50% in 43.9%, seizure frequency reduction of <50% in 23.5%, no change in seizure frequency in 6.1% and worsening of seizure frequency in none (Figure)
• Patients with shorter epilepsy duration had a better response effect for lacosamide addition, compared with longer epilepsy duration (6.2 vs 12.2, p = 0.002)
• A higher percentage of patients were on a combination of valproic acid and LCM (36.2%) as compared to levetiracetam and LCM (13%)
• Add-on lacosamide was associated with retention rates of 99.1% at the 3-month follow-up and 93.3% at the 6-month follow-up.

Figure : Efficacy of LCM at 6 months

Safety 

• Adverse events were mild to moderate and tolerable
• The overall incidence of adverse events was 35.8%
• No significant differences were seen in the daily LCM doses in patients experiencing adverse events and those without
• The leading AEs were dizziness (16.98%), sedation (6.6%) and fatigue (6.6%)
• Most of the laboratory examinations were within the normal range, with non-significant changes

Conclusion

Adjunctive LCM was efficacious and tolerable in real-life conditions in patients with focal-onset seizures, with or without combined secondarily generalized seizures.

Acta Neurologica Belgica 2023; 123: 1081-1087