Anti-epileptic drug intake adherence: the value of the blood drug level measurement and the clinical approach

Abstract

-It was evaluated the patient antiepileptic drug (AED) intake adherence in a pilot cross-sectional study carried out at a neurologic out-patient clinic of a university hospital. Ninety-three AED blood concentration (phenobarbital, phenytoin, carbamazepine) were analyzed from 24 patients. The variability of the AED blood level was measured (in the steady state period by means of the variation coefficient) and compared with the selfreported antiepileptic medication non-adherence, AED blood level according to the range (therapeutic or not), and the seizure control. It was not observed any strong correlation between the higher value of variability and the other three parameters of no adherence. The highest correlation was with the blood drug level (therapeutic or not). The evaluation of blood drug measurement alone, except in cases of extreme low adherence and variability of drug intake, is not enough for the recognition of incorrect drug intake, but the clinical markers and the selfreported adherence have to be also considered for this sort of evaluation.KEY WORDS: epilepsy, adherence, therapeutic blood monitoring, antiepileptic drugs. Aderência à ingestão de medicamentos antiepilépticos: o valor da avaliação dos níveis sanguíneos e a abordagem clínicaRESUMO -Avaliou-se a aderência à ingesta de drogas antiepilépticas (DAE) em estudo piloto transversal conduzido em ambulatório de hospital neurológico universitário. Noventa e três amostras sanguíneas com concentração de DAE (fenobarbital, fenitoína, carbamazepina) foram analisadas de 24 pacientes. A variabilidade dos níveis sanguíneos das DAE (em estado estável -steady state period, analizada por meio do coeficiente de variação) foi comparada com a auto-referida não aderência à ingesta da DAE, níveis sanguíneos das DAE de acordo com a faixa (terapêutica ou não) e o controle das crises epilépticas. Não foi observada correlação forte entre o maior valor da variabilidade e os outros três parâmetros de aderência, apesar da maior correlação com o nível sanguíneo (terapêutico ou não). A avaliação do nível sérico isolado, exceto em caso de extrema baixa aderência e variabilidade da ingesta das DAE, não é suficiente para o reconhecimento da ingesta inadequada, mas os marcadores clínicos e a auto-aderência referida também têm que ser consideradas para esse tipo de avaliação.PALAVRAS-CHAVE: epilepsia, aderência, monitorização de níveis sanguíneos, drogas antiepilépticas.Poor adherence is considered the most important cause for unsuccessful treatment in epilepsy. Consequently, drug intake adherence is a fundamental process in effective therapy, and in clinical practice its measurement has to be done frequently to apply adherence-improving interventions [1][2][3][4][5][6][7][8] .

Evaluation of Kilifi Epilepsy Education Programme: A randomized controlled trial

“…The detectable ranges for the different drugs were the following: phenobarbital 1.1 μg/mL, phenytoin 1.0 μg/mL, and carbamazepine 0.5 μg/mL . The optimal ranges were defined as follows: phenobarbital 10–40 μg/mL, phenytoin 10–20 μg/mL, and carbamazepine 4.0–12 μg/mL . An individual was defined as adherent if AEDs were detectable in their blood, and improved adherence if the AED levels were within the optimal levels at follow‐up.…”

Measures of adherence to epilepsy treatment: Review of present practices and recommendations for future directions

“…A drop in medication level of a certain predetermined percentage, dependent on study and medication being studied, is indicative of noncompliance. Sample sizes for blood plasma or serum studies have ranged from 24 patients (Gomes et al, 1998) to as many as 264 (Landmark et al, 2007).…”

“…Gauging blood medication levels is not exact, with the main concern being variability in evaluations. Several factors have been linked to variability in blood levels for a single patient, including age, food intake, and drug interaction (Gomes et al, 1998). Serum levels also vary according to drug taken.…”

Identification and Prevention of Antiepileptic Drug Noncompliance: The Collaborative Use of State-Supplied Pharmaceutical Data

“…The current consensus on TDM is that each patient should be treated on an individual basis as disease severity and drug response are highly variable [29, 30]. The Scottish Intercollegiate Guidelines Network (SIGN) number 70 [31] states that the use of TDM should not be routine.…”