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Causality: well established
Causality assessment · Causality: well established
Donepezil (cholinesterase inhibitors) and Bradycardia / syncope: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Donepezil (cholinesterase inhibitors) ↔ Bradycardia / syncope
n=1,014 co-reports · PRR 11.2 · ROR 11.5
Donepezil boosts acetylcholine by inhibiting cholinesterase, and because the vagus nerve uses acetylcholine to slow the heart, it can cause bradycardia, heart block, and syncope — effects that are easy to miss in older patients who may simply fall. This is why the drug's labelling cautions about heart-rate-lowering, and why clinicians watch for dizziness and falls. The 1,014 co-reports (PRR 11.2) reflect both the real effect and the very large, elderly population taking cholinesterase inhibitors.
Regulatory basis: donepezil prescribing information (bradycardia, heart block, and syncope cautions). Established cholinesterase-inhibitor bradycardia literature.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Bradycardia/syncope occur during treatment and resolve after withdrawal |
| Strength | met | PRR 11 on a large co-report count |
| Consistency | met | Reproduced across cholinesterase inhibitors and in cohort studies |
| Specificity | met | A class effect of cholinesterase inhibitors |
| Biological gradient | partial | Risk rises with dose and in patients with cardiac conduction disease |
| Plausibility | met | Increased vagal (acetylcholine) tone slows the SA/AV nodes |
| Coherence | met | Coheres with the labelled cardiac cautions and falls risk |
| Experiment | partial | Dechallenge (withdrawal) reverses it; a large trial recorded bradycardia events by arm |
| Analogy | met | Analogous to bradycardia with other cholinesterase inhibitors |
This page's own qualitative read, not an automated/citation-gated assessment.
✗ A large donepezil trial that posted results (NCT02079246) tracked bradycardia and syncope but recorded only single serious events, mostly in the active arm — too few to quantify, so the risk rests on the labelled caution and cohort studies rather than a trial AE table.