Polymorphisms in ABCB1 and EPHX1 genes influence drug effectiveness in refractory epilepsy: a retrospective study

Written by Lopez-Gongora M, Miralles M, Martinez-Domeño A, Vidal N, Espadaler J & Escartin A

Aim: Thirty percent of epileptic patients are refractory to treatment. We investigated the association between the number of seizures in refractory epileptic patients and potential interactions between their antiepileptic medications (AEDs) and single nucleotide polymorphisms in genes ABCB1, CYP2C9 and EPHX1. Methods: Thirty-three adult patients were included and tested for genetic variations using the Neuropharmagen® test. Retrospective data on AED therapy and number of seizures during the 12 months before inclusion were extracted from clinical records. Results: Patients displaying potential single nucleotide polymorphisms × AED interactions had a median of 14.5 seizures during the previous 12 months (IQR 5.5–105.0), compared to a median of 7.0 seizures (IQR 4.0–12.0) in patients without these interactions (univariate p = 0.051, adjusted p = 0.034). Conclusion: Refractory patients carrying genetic variations potentially affecting their AED medication experienced a significantly higher number of seizures. Thus, genotyping could help to better control epilepsy in some refractory patients.
Epilepsy is the most common serious neurological disorder worldwide, affecting around 70 million people [1]. Currently, the clinical decision process for selection of an antiepileptic drug (AED) is predominately based on the patient’s epileptic syndrome and side effect profiles of the AEDs. However, one of the most frustrating aspects of treating people with epilepsy is the inability to predict who will respond to antiepileptic drugs and who will be treatment-resistant [2]. Thus, the standard care of patients in antiepileptic treatment is more or less based on trial and error. The prediction of AED effectiveness would be important for approximately 30% of drug-resistant patients who do not respond to two adequate trials of tolerated AEDs [3,4,5].

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