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.