Value of drug level concentrations of brivaracetam, lacosamide, and perampanel in care of people with epilepsy.

OBJECTIVE: The aim of this study was to determine whether clinical efficacy and reported adverse effects (AEs) of the newer antiseizure medications (ASMs) brivaracetam (BRV), lacosamide (LCM), and perampanel (PER) have been associated with plasma levels of these ASMs. We also investigated whether plasma levels outside the reference range has 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 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 = .243; PER, p = .113) or responder status (BRV, p = .118; LCM, p = .478; PER, p = .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 interindividual variability. Instead, individual reference values should be established when sufficient clinical data are available, in line with the 2008 International League Against Epilepsy position paper on therapeutic drug monitoring.

Psychosocial assessment of living kidney donors: What implications have temperament and character for decision-making?

OBJECTIVE: We compared the personality of kidney donor candidates to non-donor controls and analyzed the personality profile of candidates psychosocially at risk. METHODS: 49 consecutive living kidney donor candidates underwent an extensive psychosocial evaluation. Psychosocial risk factors concerning knowledge of donation risks (1), donor-recipient-relationship (2), and/or mental health (3) were rated on a 3-point rating scale (0=high risk, 2=no risk). Furthermore, candidates as well as 49 age-and gender-matched non-donor controls filled in questionnaires concerning psychological distress (Symptom Checklist 90-R) and personality (Temperament and Character Inventory). RESULTS: There were no significant differences between candidates and controls concerning psychological distress or personality. Psychosocial assessment identified 13 candidates (26.5%) with increased psychosocial risk. This group displayed compared to candidates without psychosocial risk no difference concerning age, gender, formal education, donor-recipient relationship and psychological distress. However, this group scored significantly higher on reward dependence compared to suitable donors and controls (p<0.05). Reward dependence was associated with a lack of adequate knowledge on donation (r=-0.35, p<0.05). CONCLUSION: Reward dependence has important implications for decision-making, because it is associated with an increased tendency to deny potential risks of donation. Careful identification and assessment of reward dependent donor candidates is needed to ensure a free-willed decision.