Evaluation of Cardiac Repolarization Indices in Epilepsy Patients Treated with Carbamazepine and Valproic Acid

Abstract

Background and Objectives: Epilepsy patients have a higher risk of sudden unexplained death compared to the rest of the population. Cardiac repolarization abnormalities might be seen in epilepsy during interictal periods. We aimed to evaluate the changes in electrocardiography (ECG) parameters in generalized tonic-clonic seizure patients treated with carbamazepine or valproic acid (VPA) drug. Materials and Methods: A totally of 129 subjects (66 epilepsy patients, 63 healthy subjects) were enrolled in the study. Of the patients, 36 were on carbamazepine and 30 were on VPA. There were 12-lead ECGs obtained from all participants. RR interval (time between consecutive R peaks), QT interval (defines the period of ventricular repolarization), corrected QT (QT interval corrected for heart rate; QTc), QTc-maximum (QTc-max), QTc-minimum (QTc-min), QTc dispersion (QTcd), P (atrial depolarization )-maximum (P-max), P-minimum (P-min) and P dispersion (Pd) were measured. Results: QTd (QT dispersion), QTcd, and Pd values were significantly higher in the patients compared to the controls (p < 0.01). QTcd, Pd, and P-max values were statistically higher in male patients compared to healthy male controls. QTcd values were significantly higher in female patients using carbamazepine compared to the female patients on VPA and healthy controls (p = 0.01). Male patients using VPA had significantly higher QTcd values against the male population in carbamazepine and control groups. Conclusions: This study demonstrated that QTd, QTcd, and Pd values were significantly higher in epilepsy patients than in healthy controls. In addition, female patients using carbamazepine and male patients using VPA were prone to ventricular arrhythmia compared to the control group.

Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na+ and Erg-Mediated K+ Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line

“…Of additional notice, although CBZ is safe and effective in anti-convulsant activities, the unwanted events following CBZ treatment, such as hyponatremia, QT-interval prolongation, hyperprolactinemia, change in pitch perception and idiosyncratic reactions, have gradually emerged [ 5 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The effectiveness of CBZ in inhibiting the activity of ATP-sensitive K + (K ATP ) channels has also been demonstrated [ 29 , 30 ].…”

Valproic acid and prolonged QT: highlights from the FDA Adverse Event Reporting System FAERS database

“…Asoğlu et al demonstrate that QT dispersion, QTcd (QT interval corrected for heart rate dispersion) and Pd (atrial depolarization dispersion) values are significantly higher in epileptic patients using carbamazepine and valproic acid than in the healthy control group. They also report that female patients using carbamazepine and male patients using valproic acid have QTcd values significantly higher compared to female population in valproic acid or male patients on carbamazepine [1].…”

“…A prolonged QT interval is suggestive of repolarization abnormalities; it can be associated with an increased risk of torsade de pointes (TdP), that can lead to ventricular fibrillation and sudden cardiac death (SCD) and it is considered a marker of arrhythmia [1][2][3].…”

“…It exerts antiepileptic effects by suppressing the high-frequency neuronal firing by voltagesensitive sodium, potassium and calcium channel blockade [14]. The association between valproate and prolonged QT interval is still not clear [1,6,7,15], so that in clinical practice pharmacological counselling is often requested on a possible involvement of valproic acid in the onset this side effect.…”

Carbamazepine-Induced Symptomatic Bradycardia in a Middle-Aged Female

“…4,6 Because carbamazepine has the property of moderating the phase 4 depolarization of the pacemaker cells, it tends to suppress the rhythm aggravating bradycardia of a complete heart block. 7 Cardiac conduction problems are more commonly reported in old female patients, 8,9 however, there are also some cases noted in old male patients such as in the study done by Celik et al wherein a 2:1 atrioventricular block was observed in a 56-year old man who was given carbamazepine 400 mg/day for 15 months for treating temporal lobe epilepsy. 10 Although the majority of the reported cases of carbamazepine-induced arrhythmia are observed in old female patients, a few incidents have been reported in middle-aged and young patients.…”