Minimizing pharmacodynamic interactions of high doses of lacosamide

Objectives- To determine whether pharmacodynamic interactions between high doses of lacosamide (400-800mg/day) and concomitant sodium channel antiepilepsy drugs (AEDs) can be minimized in patients with drug-resistant partial-onset seizures. Materials and methods- Patients were rapidly initiated with high-dose lacosamide (100mg/week; increases to 400 to 800mg/day), while simultaneously tapering concomitant sodium channel AEDs. Seizure frequency and side effects were evaluated at six time points: baseline, titration, 3, 6, 9 and 12months. Results- Twenty-three patients had a baseline median of 4seizures/month with persisting partial-onset seizures, despite previous treatment with an average of 6.8 AEDs. Mean decreases in monthly seizure frequency were as follows: 3months 49.9% (P=0.011), 6months 55.4% (P=0.010), 9months 60.8% (P=0.002) and 12months 58.2% (P=0.011). Most adverse events were mild CNS-related symptoms and occurred transiently only during titration - there was no significant relationship (χ ²<1.5, P>0.1) between lacosamide dose and the presence of side effects at 3, 6, 9 or 12months. Conclusion- s - Drug-resistant patients rapidly titrated to high doses of lacosamide with simultaneous tapering of traditional sodium channel AEDs had marked reduction in CNS-related adverse events compared with patients treated in three previous pivotal trials that used fixed doses of concomitant AEDs.