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

Abstract

SUMMARYPurpose: 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.

Effect of lamotrigine on the PR interval in healthy subjects

“…In the carbamazepine comparator group, the mean change from baseline was larger (14.1 ms) than on lamotrigine. Comparison of our data with that of the paper by Saetre et al [3] is limited by the absence of placebo in their study. Furthermore, the population has some important differences compared with the young healthy volunteer population in our study, being comprised of elderly subjects with epilepsy, some of whom had significant cardiovascular co-morbidities and frequent concomitant medications.…”

“…In a more recent paper by Saetre et al [3], the mean change from baseline in PQ interval after 40 weeks of treatment with lamotrigine (n = 29, mean dose of 111 mg) was an increase of 8.8 ms, although the median change from baseline was zero. The mean plasma lamotrigine concentration was 2.64 mg ml -1 .…”

Enhanced QT shortening and persistent tachycardia after generalized seizures

“…Although the use of carbamazepine could have influenced our results, this drug is associated with bradyarrhythmias and has only minor effects on QT intervals. 31,32 Further, QTc was normal during interictal periods and also we compared the effects of different seizure types within individual patients.…”

Clinical results of and prospects for the use of controlled-release antiepileptic drugs: a new once-daily levetiracetam formulation

“…1, в двух исследованиях со сходным дизайном удержание на карбамазепине (КБЗ) ДВ практически не отличается от удержания на ламотриджине (ЛТД). При этом длительность наблюдения в исследова-нии В [7] почти в 2 раза превышала таковую в исследова-ния А [8].…”