Introduction
Donepezil is an acetylcholinesterase inhibitor primarily used to treat
mild to moderate Alzheimer’s dementia (AD). While the neurocognitive
benefits of donepezil are well documented, its adverse affects on
cardiac conduction remain unclear. Several case studies have reported QT
prolongation and subsequent Torsades de Pointes (TdP) associated with
donepezil use in patients with AD (Kitt & Irons et al., 2015; Mandal &
Khan et al., 2019; Malik & Hamid et al., 2019; Takaya & Okamoto et
al., 2009) while others have reported bradycardia and PR prolongation,
resulting in subsequent medication cessation (Bordier & Garrigue et
al., 2003; Hernandez & Farwell et al., 2009). Smaller scale studies to
date have shown that donepezil is relatively safe to use in the older
population. Common parasympathetic side-effects have been associated
with its use, but importantly these small-scale observational studies
have not reported any sinister cardiac conduction abnormalities such as
significant QT prolongation, subsequent arrhythmia or syncopal episodes
(Bordier & Garrigue et al., 2006; Igeta & Suzuki et al., 2014; Wang &
Wu et al., 2018).
The British National Formulary (BNF, 2020) describes bradycardia as an
uncommon side-effect and cardiac conduction disorders to be a rare, or
very rare side effect of donepezil. First-degree atrioventricular (AV)
block and supraventricular tachycardia were reported to be infrequent
side-effects by the United States Food and Drug Administration (FDA,
2020). Physicians are advised to practise caution when prescribing
donepezil in patients with cardiac conduction disorders, but despite
these warnings there remains on-going debate as to whether a resting
12-lead electrocardiogram (ECG) is required prior to initiation of
donepezil therapy (Rowland & Rigby et al., 2007).
The primary objective of our study is to investigate whether ECG changes
are associated with donepezil therapy and in particular assess its
effects on the QT interval. We also aim to evaluate whether gender,
treatment duration, donepezil dose or concomitant use of medications are
associated with conduction abnormalities and QT prolongation in patients
prescribed donepezil therapy.