Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy

PURPOSE Recent reports have documented the appearance of Brugada-type ST elevation in cases of overdose of antiepileptic drugs (AEDs). However, little is known about changes on electrocardiographs (ECGs) during AED use at therapeutic doses. AEDs may cause Brugada-type ST elevation or J-wave-like intraventricular conduction delays through an ion channel-blocking effect. In the present study, we sought to elucidate ECG abnormalities in patients on AED therapy. METHODS The study population consisted of 120 consecutive patients with epilepsy who continued to take AEDs and had ECGs recorded during these therapies. Their clinical background and ECGs were retrospectively analyzed. Brugada-type ST elevation was classified according to the consensus report on Brugada syndrome. A J-wave-like ECG abnormality was defined as the appearance of notching or slurring of the QRS complex (>0.1mV) in the inferior/lateral leads. RESULTS Of the 120 patients, 15 (12.5%) exhibited Brugada-type ST elevation and 35 (29.2%) showed a J-wave-like ECG abnormality. Polytherapy with sodium channel-blocking AEDs (e.g., carbamazepine, phenytoin, lamotrigine) was more frequently observed in patients with Brugada-type ST elevation (p=0.048). However, the serum concentrations of these medicines did not differ between patients with and without ECG abnormalities (carbamazepine: 7.9±4.1 vs. 7.2±5.9μg/dL; phenytoin: 12.7±4.1 vs. 15.5±9.5μg/dL, NS). CONCLUSION ST-T abnormalities were frequently seen in patients using AEDs. The presence of Brugada-type ST elevation was associated with polytherapy with sodium channel-blocking AEDs.