The value of drug level concentrations of brivaracetam, lacosamide and perampanel in the care of people with epilepsy.

OBJECTIVES: The aim of this study was to determine whether clinical efficacy and reported adverse effects (AEs) of the newer anti-seizure medication (ASM) brivaracetam (BRV), lacosamide (LCM) and perampanel (PER) were associated with plasma levels of these ASMs. We also investigated whether plasma levels outside the reference range led to dose adjustments.

METHODS: Plasma levels of 300 people with epilepsy (PWE) seen at our tertiary epilepsy center were determined by liquid chromatography-tandem mass spectrometry. PWE received either BRV (n=100), LCM (n=100) or PER (n=100), in most cases in polytherapy. Demographic and clinical data were retrospectively analyzed and related to plasma levels. Clinical efficacy of BRV, LCM or PER was assessed retrospectively by comparing seizure frequency at the time of current blood draw with seizure frequency at the time of first administration. AEs were also recorded and, if reported, compared retrospectively with the time of first administration.

RESULTS: No significant associations were found between plasma levels of BRV, LCM or PER and seizure freedom (BRV p=1.000, LCM p=0.243, PER p=0.113) or responder status (BRV p=0.118, LCM p=0.478, PER p=0.069) at presentation. There was also no pattern between plasma levels and the occurrence of AEs. In the majority of cases, drug levels outside the reference ranges have not led to adjustments in the daily doses of BRV (93.5%), LCM (93.9%) or PER (89.1%).

SIGNIFICANCE: Plasma levels at a given time point did not allow conclusions to be drawn about seizure control or the occurrence of AEs. Our findings indicate that efficacy and tolerability cannot be predicted based on averaged data from a single plasma measurement due to high inter-individual variability. Instead, individual reference values should be established when sufficient clinical data are available, in line with the ILAE position paper, 2008, TDM.