Long term use of donepezil and QTc prolongation

The neurocognitive benefits of donepezil are well recognised, but the potential side effects on cardiac conduction remain unclear.

To investigate whether long-term donepezil therapy is associated with electrocardiographic (ECG) changes and in particular to assess its effects on the QT interval.

We conducted a single centre retrospective analysis of patients admitted to our trust on donepezil therapy over a 12-month period. 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.

We identified 59 patients suitable for analysis. PR (177.0 ± 29.0 ms vs. 186.1 ± 34.2 ms, p = 0.04), QRS (101.7 ± 20.3 ms vs. 104.7 ± 22.3 ms, p = 0.04) and QT (393.3 ± 35.6 ms vs. 411.9 ± 44.6 ms, p = 0.002) interval prolongation were all associated with donepezil use. 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 (QTcB: r _pb = 0.344, p = 0.008, QTcFred: r _pb = 0.382, p = 0.003, QTcFram: r _pb = 0.379, p = 0.003, QTcH: r _pb = 0.352, p = 0.006), while the use of rate-limiting calcium channel blockers was associated with significant PR prolongation (r _pb = 0.314, p = 0.030), and beta-blockers with a reduction in heart rate (r _pb = 0.256, p = 0.050).

Our results clearly demonstrate that long-term use of donepezil is associated with 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.