Adjunctive lacosamide--5 years' clinical experience

Abstract

Purpose: In 2008, lacosamide (LCM) was licensed in Europe for the adjunctive treatment of focal-onset seizures. At that time a prospective audit was initiated at the Western Infirmary to assess outcomes with this antiepileptic drug (AED) in everyday clinical practice.

Methods: A total of 160 patients (74 M; 86 F, aged 14-74 years [median 42 years]) with uncontrolled focal-onset seizures (median monthly frequency 1; range 1-300) were started on LCM. After 12 weeks on stable AED doses (median 1 AED; range 1-4), LCM was added and the dose titrated as appropriate with a target range of 200-400 mg/day. Review took place every 6-8 weeks until 1 of 4 end-points was reached: seizure freedom for 6 months on a given LCM dose; ≥50% (responder) or <50% (marginal benefit) seizure reduction over 6 months compared with baseline on the highest tolerated LCM dose; withdrawal of LCM due to lack of efficacy, side effects, or both.

Results: Of the 160 patients, 35 (21.9%) remained seizure-free for at least 6 months on a stable LCM dose, while 35 (21.9%) had a ≥50% reduction in seizure frequency and 54 (33.7%) reported a marginal benefit. Five patients became seizure-free on LCM monotherapy following withdrawal of their initial treatment. Outcomes were similar for patients taking LCM with traditional sodium blocking agents (n=56; 43 [76%] continued LCM) compared to those who also received AEDs with other mechanisms (n=84; 64 [76%] continued LCM). LCM was discontinued in 36 (22.5%) patients because of lack of efficacy (n=24, 15%) or side effects (n=12; 7.5%). Commonest side effects leading to withdrawal were nausea and vomiting, dizziness, sedation, headaches, tremor, and ataxia, particularly for patients also taking sodium valproate.

Conclusion: LCM is a well-tolerated and effective AED for focal-onset seizures with or without secondary generalisation, regardless of concomitant treatment. Commonest dose-related side effects were neurotoxic in nature.

Keywords: Adjunctive; Epilepsy; Focal; Lacosamide; Outcomes; Seizures.