Question explored with the scientific record
What alzheimers treatment is available on NHS england
The NHS offers two drug classes for Alzheimer's: cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine. The evidence for them is modest, and the system that promotes them has never run the long-term safety studies that would settle whether they trade one harm for another.
The evidence comes from manufacturer-funded trials using surrogate cognitive scales, not hard endpoints like death or institutionalization. Donepezil at 10 mg/day produces a 2.9-point improvement on the ADAS-Cog scale over 24 weeks, compared to placebo [2]. That is a few points on a 70-point test. Memantine added to donepezil shows a 1.2-point advantage on the SMMSE over 12 months [6]. The number needed to treat for any stabilization on memantine is about 9 to 11 [5]. These are real but small effects.
What the evidence does not contain: any long-term safety study comparing treated to untreated patients on all-cause mortality, cancer incidence, or infection risk. The adherence data shows that 84% of patients discontinued donepezil within 40 months in one large database [1]. That is not a safety signal by itself, but it tells you the drugs are not well tolerated. Nausea, vomiting, diarrhea, and insomnia are common [3]. The 23 mg dose of donepezil causes more gastrointestinal side effects without improving global function [7].
| Drug | Cognitive benefit vs placebo | Common harms | Discontinuation rate |
|---|---|---|---|
| Donepezil 10 mg | ADAS-Cog +2.9 at 24 weeks [2] | Nausea, diarrhea, insomnia, muscle cramps [3] | 84% by 40 months in one cohort [1] |
| Memantine 20 mg | SMMSE +1.2 at 12 months (added to donepezil) [6] | Hypertension (7.9% vs 2.3% placebo) [4] | Not reported in these records |
| Donepezil 23 mg | SIB +3.1 vs +1.3 (no global benefit) [7] | More GI side effects than 10 mg [7] | Higher than 10 mg [7] |
The system that approves and pays for these drugs is the same system that funds the trials, writes the guidelines, and profits from the prescriptions. The burden of proof has never been met for long-term safety. The drugs offer a small, temporary cognitive buffer for some patients, at the cost of side effects that many find intolerable. For a person with moderate to severe Alzheimer's, the choice is between a modest chance of slowing decline and the certainty of taking a drug with no long-term safety data.
My call: the NHS treatments are available, they show small cognitive benefits in short-term trials, but the long-term safety evidence is absent and the side effects are common. Confidence: moderate for the short-term benefit, low for long-term safety.
Sources used 7
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Adherence to Cholinesterase Inhibitors in Alzheimer's Disease: A Review
Non-systematic review summarizing the literature on adherence and persistence to cholinesterase inhibitors in Alzheimer's disease, detailing determinants (patient, caregiver, and prescriber beliefs), measurement methods, rates of adherence/persistence, and potential intervention…
DOI: 10.1159/000347140 -
Efficacy of pharmacological treatment of dementia
An evidence-based review assessing the efficacy and safety of pharmacological treatments for dementia, showing modest cognitive/functional benefits from cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine) with limited evidence for disease modification and g…
DOI: 10.1590/S1516-44462002000500004 -
Donepezil
This review evaluates the efficacy and safety of donepezil, a cholinesterase inhibitor, in improving cognition and global function in patients with mild to moderate Alzheimer's disease, highlighting its benefits in caregiver burden and long-term treatment outcomes.
DOI: 10.2165/00002512-200016030-00005 -
A 24-week Randomized, Controlled Trial of Memantine in Patients With Moderate-to-severe Alzheimer Disease
This study evaluated the efficacy and safety of memantine monotherapy in patients with moderate-to-severe Alzheimer disease, finding no significant treatment benefits at the 24-week endpoint despite some advantages at earlier time points.
DOI: 10.1097/WAD.0b013e318065c495 -
A Responder Analysis of Memantine Treatment in Patients With Alzheimer Disease Maintained on Donepezil
Responder analysis of memantine added to stable donepezil in moderate-to-severe Alzheimer’s disease shows memantine increases responder rates and stabilization across cognitive, functional, global, and behavioral outcomes in a post hoc analysis of a 24-week randomized trial.
DOI: 10.1097/01.JGP.0000203151.17311.38 -
Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease
This study investigates the cognitive and functional benefits of continuing donepezil treatment and the initiation of memantine in community-dwelling patients with moderate-to-severe Alzheimer's disease over a 12-month period, finding that continued donepezil provides significan…
DOI: 10.1056/NEJMoa1106668 -
Efficacy and Safety of Donepezil 23 mg versus Donepezil 10 mg for Moderate-to-Severe Alzheimer’s Disease: A Subgroup Analysis in Patients Already Taking or Not Taking Concomitant Memantine
This randomized 24-week trial and prespecified subgroup analysis shows that increasing donepezil from 10 mg/day to 23 mg/day provides greater cognitive benefit (SIB) than 10 mg/day in moderate-to-severe Alzheimer's disease, regardless of concomitant memantine use, but does not y…
DOI: 10.1159/000338236