Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained-release carbamazepine

Purpose: To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy. Methods: The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double-blind 40-week trial, which compared the efficacy and tolerability of LTG and sustained-release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12-lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40-week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR-corrected QT) intervals were assessed and compared between groups. Results: Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline. Discussion: Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects.