Cholinesterase inhibitors: symptomatic treatment in dementia
Donepezil, rivastigmine and galantamine inhibit acetylcholinesterase, increasing acetylcholine at synapses. They may offer modest symptomatic benefit for cognition/function in selected people with Alzheimer disease and, for rivastigmine, Parkinson disease dementia. They do not reverse neurodegeneration. Good care also needs diagnosis, carer support, vascular-risk management, delirium prevention and realistic treatment goals.
Before prescribing
Check pulse, syncope/falls, conduction disease, asthma/COPD, weight loss, peptic-ulcer/GI-bleed risk, bladder outflow obstruction, seizures and anticholinergic medicines. Cholinergic effects can cause bradycardia, vomiting, fainting and weight loss.
1. Drug comparison and dose titration
| Medicine | Typical adult initiation | Titration and monitoring |
|---|---|---|
| Donepezil | 5 mg orally once daily, often at night (move to morning if vivid dreams/insomnia). | After at least 4–6 weeks, increase to 10 mg once daily if tolerated. Typical maximum for mild–moderate disease is 10 mg/day; 23 mg is a specialist/product-specific option for selected severe disease after stable 10 mg treatment. |
| Rivastigmine oral | 1.5 mg twice daily with food. | Increase slowly, commonly at ≥2-week intervals, to tolerance. GI adverse effects are common; stop and reassess significant vomiting/weight loss. |
| Rivastigmine patch | 4.6 mg/24 h patch once daily on intact skin. | Increase after at least 4 weeks if tolerated (often to 9.5 mg/24 h; selected patients to 13.3 mg/24 h). Apply only one patch; remove the old patch first. If interrupted >3 days, restart at 4.6 mg/24 h and retitrate. |
| Galantamine | Formulation-dependent; commonly 4 mg twice daily immediate-release or 8 mg daily modified-release. | Titrate slowly with food and hydration; check renal/hepatic suitability and CYP interactions. |
2. Adverse effects and interactions
Expected cholinergic effects include nausea, vomiting, diarrhoea, anorexia, weight loss, sweating, vivid dreams and muscle cramps. Serious concerns include bradycardia, heart block, syncope, falls, GI bleeding, bronchospasm and seizures. Review beta-blockers, digoxin and other rate-slowing medicines; also review anticholinergic drugs, which can oppose cognitive benefit and worsen confusion.
3. Patch and oral-medicine counselling
- For a patch: remove yesterday’s patch before applying one new patch; rotate sites; avoid damaged skin and external heat; seek help for severe rash.
- Take oral agents with food where advised; report persistent vomiting, black stool, fainting or markedly reduced intake.
- Do not use the medicine as a substitute for supervision, falls prevention, driving review, carer support or assessment of acute confusion.
- New confusion over hours/days is delirium until proven otherwise—look for infection, medicines, dehydration, pain, constipation and metabolic causes.
4. Cholinesterase inhibitors beyond dementia
Neostigmine and pyridostigmine are also acetylcholinesterase inhibitors, used in different clinical contexts such as myasthenia gravis or reversal of non-depolarising neuromuscular blockade. They are not interchangeable with donepezil/rivastigmine. Excess cholinergic effect can produce salivation, sweating, bronchospasm, bradycardia, abdominal cramps, diarrhoea, miosis and weakness; emergency treatment is protocol- and cause-specific.
OSCE checklist
Confirm dementia subtype and treatment goal; obtain collateral history; check pulse, weight, falls/syncope, GI and respiratory history; review rate-slowing and anticholinergic medicines; explain slow titration and the expected modest symptomatic role; give patch-specific instructions where relevant; agree a review date and carer safety-net.
