Abstract
Background and Purpose: The neurocognitive benefits of donepezil are
well recognised, but the potential side effects on cardiac conduction
remain unclear. Our objectives are to investigate whether long-term
donepezil therapy is associated with electrocardiographic (ECG) changes
and in particular to assess its effects on the QT interval. Experimental
approach: We conducted a single centre retrospective analysis of
patients admitted to our institution on donepezil therapy over a
12-month period. 59 patients were identified as suitable for analysis.
An admission resting 12-lead ECG was obtained and compared to their ECG
prior to commencement of donepezil therapy to assess for any significant
difference in ECG parameters. Key Results: Donepezil significantly
prolonged the PR (P=0.04), QRS (P=0.04) and QT (P=0.002) intervals. The
increase in QT intervals remained significant on correction for heart
rate; resulting in 8 (13.6%) patients developing high arrhythmogenic
risk based on assessment using QT nomogram plots. Concomitant use of
tricyclic antidepressants was associated with significant QT
prolongation, while use of rate limiting calcium channel blockers was
associated with significant PR prolongation, and beta-blockers with
reduction in heart rate. Conclusion and Implications: Our results
clearly demonstrate that long-term use of donepezil results in
prolongation of the QT interval. We suggest ECG evaluation should take
place before and after donepezil initiation, and clinicians should be
even more vigilant in those prescribed tricyclic antidepressants.