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Alzheimer's Disease — MRCPsych Paper B MCQ

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ModerateOld Age PsychiatryAlzheimer's DiseaseMRCPsych Paper B

A 75-year-old woman with moderate Alzheimer's disease has her donepezil increased from 5 mg to 10 mg daily. Ten days later, she has a syncopal episode. Her pulse, which was 68 beats/min before dose escalation, is now 48 beats/min. ECG shows sinus bradycardia without sinoatrial pauses or atrioventricular block. She takes no other rate-limiting medication, is clinically euvolaemic, has no cardiac murmur, and has normal serum electrolytes and thyroid function. What is the most likely cause?

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Correct answer: A — Donepezil adverse effect

The correct answer is A: donepezil adverse effect. Acetylcholinesterase inhibition increases cholinergic activity and can exert a vagotonic effect on the sinoatrial and atrioventricular nodes, causing bradycardia, syncope or conduction block. The close relationship to dose escalation and previously normal pulse are particularly discriminating. Sick sinus syndrome can cause bradycardia and syncope, but there is no prior history or ECG evidence of sinoatrial pauses, and the medication-related temporal association is stronger. Hypothyroidism is excluded by normal thyroid function. Aortic stenosis would usually be suggested by an ejection systolic murmur, while dehydration would more typically produce volume depletion, orthostatic hypotension and compensatory tachycardia.

Reference: Electronic Medicines Compendium, Donepezil Hydrochloride 5 mg Film-coated tablets, Summary of Product Characteristics, sections 4.4 and 4.8, updated 2024. https://www.medicines.org.uk/emc/product/4428/smpc