Seizure freedom and plasma levels of newer generation antiseizure medications.

Objectives: Contrary to older antiseizure medications (ASM), correlation between plasma levels and seizure freedom is not well defined for newer generation ASM. We assessed correlations between efficacy and newer generation ASM plasma levels in patients with epilepsy.

Materials And Methods: Plasma medication levels were measured over two years in consecutive patients taking lamotrigine, levetiracetam, oxcarbazepine, topiramate, zonisamide, lacosamide, perampanel or pregabalin. Seizure freedom was defined as three times the longest inter-seizure pre-treatment interval, or at least one year. Each medication level was stratified according to its position in relation to its proposed reference range (below or in lower half vs upper half or above).

Results: 168 patients on stable therapy were included. ASM plasma levels of seizure-free patients were lower than those with ongoing seizures; 45/48 (93.7%) were in the lower half or below the reference ranges, compared to 86/106 (81.1%; p = .004). Lamotrigine plasma levels were significantly lower in seizure-free patients (median 2.4 mg/L range 0.4-6.5 mg/L, none above 6.5 mg/L) compared with those with ongoing seizures (5 mg/L, 0.5-14.2 mg/L; p < .0001). Levetiracetam showed similar results (7.2 mg/L, 1.6-15.1 mg/L; none above 15.1 mg/L in seizure-free patients vs 16.4 mg/L, 0.6-47.7 mg/L; p = .005). Demographics, epilepsy type and polytherapy did not influence the results.

Conclusions: Efficacy of newer generation ASMs seems to be reached at the lower part or at times even below the reference ranges in drug responsive patients; this could inform regarding titrations of these treatments.