Adjunctive lacosamide in clinical practice: sodium blockade with a difference?

Abstract

Lacosamide (LCM) was licensed in the United Kingdom in 2008 for the adjunctive treatment of partial-onset seizures. It exerts its effect by enhancing sodium channel slow inactivation. This article reports preliminary outcomes with adjunctive LCM in the everyday clinical setting. To date, 113 patients (57 males, 56 females; aged range=18-74 years, median=39 years) with uncontrolled partial-onset seizures (monthly frequency range=1-300, median=4) have been included in the audit. Patients were taking 1-4 (median=1) antiepileptic drugs (AEDs), having previously tried 1-12 (median 3) drug schedules. After 12 weeks on stable AED dosing, LCM was added, aiming at an initial target range of 200-400mg/day. Review took place every 6-8 weeks until one of four endpoints 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 because of lack of efficacy, side effects, or both. An endpoint has been reached by 65 (57.5%) patients so far. Seventeen (26.2%) have remained seizure free on a median daily LCM dose of 100mg (range=50-300 mg). Patients were more likely to become seizure free when LCM was used as a first add-on (15/36, 41.7%), compared with a later treatment schedule (1/27, 3.7%, P=0.001). With appropriate dose manipulation, patients taking traditional sodium blockers (5/26, 19.2%) were as likely to become seizure free as those taking AEDs with other mechanisms of action only (11/37, 29.7%). Fifty percent or greater seizure reduction was achieved in an additional 16 (24.6%) patients (1 monotherapy); 18 (27.7%) reported marginal benefit. Two patients were established on LCM monotherapy (one seizure free, one responder). Patients remaining on LCM were as likely to also be taking sodium blockers only (23/27, 85.1%) as AEDs with other mechanisms (26/36, 72.2%). LCM was withdrawn in 14 patients (12.3% of ongoing patients, 21.5% of those at an endpoint; 10 for side effects, 4 for lack of efficacy). The most common side effects leading to withdrawal were sedation, ataxia, and dizziness. Of the 10 with side effects, only 2 patients took concomitant sodium blockers. Patients on sodium valproate were more likely to discontinue LCM (8/21, P=0.018) than those also taking other AEDs; 5 of the 8 did so because of side effects and 3 because of lack of efficacy. In patients with partial-onset seizures, LCM is an effective and well-tolerated adjunctive AED when combined with appropriate doses of traditional sodium blockers, as well as agents with other mechanisms of action. Seizure freedom was more likely when LCM was used as a first add-on compared with a later treatment schedule. Patients also taking sodium valproate were significantly more likely to discontinue LCM compared with those taking other AEDs. These data suggest that the pharmacological effect of LCM differs importantly from that of AEDs that influence fast inactivation of the sodium channel.