Acetylcholinesterase (AChE) inhibitors and memantine in dementia (Guidelines)


Flow chart for the shared care of patients prescribed acetylcholinesterase (AChE) inhibitors (donepezil hydrochloride, galantamine and rivastigmine) or memantine

National guidance

The British Association for Psychopharmacology (BAP 2017) grades their recommendations (A-D) with (A) having the strongest evidence base. Table 1 summarizes these

Table 1: BAP 2017 guidelines recommendations

Type of dementia

Evidence to support

Alzheimer’s disease

AChE inhibitors for cognition in mild to severe Alzheimer’s disease (A)
Switching of one AChE inhibitor to another if the first is not tolerated or effective (B)
Memantine for moderate to severe Alzheimer’s disease (A)
Drugs should not be stopped just because dementia severity increases (A)

Lewy bodies and Parkinson’s disease dementia

Rivastigmine and donepezil for the treatment of dementia with lewy bodies and Parkinson’s disease dementia (A)
Memantine produces global improvements in Lewy body dementias, but the pattern of cognitive and neuropsychiatric responsiveness remains uncertain (B)

Vascular dementia

There is type I evidence showing small cognitive improvements with both AChE inhibitors and memantine in vascular dementia. However, benefits in terms of global outcome are not seen and adverse events for AChE inhibitors (but not memantine) are significantly greater than placebo. Evidence indicates that neither AChE inhibitors nor memantine should be prescribed to people with vascular dementia, though those with mixed vascular dementia and Alzheimer’s disease may benefit (A)

Frontotemporal dementia

AChE inhibitors are not recommended for the treatment of frontotemporal dementia (A)

Mild cognitive impairment

There is type I evidence that AChE inhibitors are not effective in reducing the risk of developing Alzheimer’s disease (A)

National Institute of Clinical Evidence (NICE NG97 2018) recommends:

  1. The three AChE inhibitors as monotherapies are recommended as options for managing mild to moderate Alzheimer's disease
  2. Memantine as monotherapy is recommended as an option for managing Alzheimer's disease for people with:
    1. Moderate Alzheimer’s disease who are intolerant or have a contraindication to AChE inhibitors
    2. Severe Alzheimer’s disease
  3. For people with an established diagnosis of Alzheimer's disease who are already taking an AChE inhibitor:
    1. consider memantine in addition to an AChE inhibitor if they have moderate disease
    2. offer memantine in addition to an AChE inhibitor if they have severe disease.
  4. Pharmacological management of non-Alzheimer's dementia
    1. Offer donepezil or rivastigmine to people with mild to moderate dementia with Lewy bodies.
    2. Only consider galantamine for people with mild to moderate dementia with Lewy bodies if donepezil and rivastigmine are not tolerated.
    3. Consider donepezil or rivastigmine for people with severe dementia with Lewy bodies
    4. Consider memantine for people with dementia with Lewy bodies if AChE inhibitors are not tolerated or are contraindicated.
    5. Only consider AChE inhibitors or memantine for people with vascular dementia if they have suspected co-morbid Alzheimer's disease, Parkinson's disease dementia or dementia with Lewy bodies.
    6. Do not offer AChE inhibitors or memantine to people with frontotemporal dementia.
    7. Do not offer AChE inhibitors or memantine to people with cognitive impairment caused by multiple sclerosis.

Both BAP and NICE guidelines recommend input from specialists for diagnosis and ongoing monitoring and outline a clear role for General Practitioners (GP) in prescribing and ongoing care.

Licensed Indications

The AChE inhibitors; donepezil, galantamine and rivastigmine are licensed for use in the treatment of mild to moderately severe Alzheimer’s disease. Oral rivastigmine is also licensed for mild to moderate dementia associated with Parkinson’s disease.

Memantine is licensed for the treatment of moderate to severe Alzheimer’s disease.

Referral Criteria

GP suspects dementia and refers patient, by electronic letter via SCI Gateway, to the sector old age psychiatrist.

The diagnosis of dementia is one of exclusion and including all the information a. to g. below on referral aids a prompt diagnosis:

  1. past medical history
  2. current medical problems
  3. current drug prescriptions
  4. social situation: - main carers, likelihood of compliance, any area of risk
  5. physical examination including weight, blood pressure and pulse. ECG if indicated.
  6. basic investigations including:
    1. Routine haematology
    2. Biochemistry (including electrolytes, calcium, HbA1c, renal and liver function)
    3. Plasma viscosity and C-reactive protein
    4. Thyroid function tests
    5. Serum B12 and folate levels
    6. Only if clinically indicated: cholesterol, urine MC&S, syphilis, HIV serology.Basic investigations including:
  7. Treat any reversible cause or contributory factor to cognitive decline

Responsibilities following referral

GP responsible for:

  1. Prescription of medication following advice from the specialist, adhering to the Adults with Incapacity Act (Scotland) 2000 where appropriate. Section 47 certificate and treatment plan completed where required.
  2. Monitor the patient for adverse effects on an ad hoc basis and report them to the specialist (and if appropriate respond to them).
  3. Medication review particularly considering effect of any anticholinergic burden and polypharmacy see: Polypharmacy Guideline
  4. Communication with the memory service on an ad hoc basis.

Memory service is responsible for:

  1. Assessment by specialist including requesting further investigations if required e.g. neuroimaging, to aid diagnosis, and/or ECG if required to make decisions regarding initiation, monitoring or titration of medication.
  2. Communication of the outcome of the assessment to the GP with recommendation to treat and prescribing regimes.
  3. Review every 6-12 months (or more frequent if clinical need necessitates) by a member of the memory service, if local resources allow. GP advised of any recommended dose or medication changes.
  4. Communication with the GP following review.
  5. Where possible verbal consent to the plan for dementia treatment will be obtained and the plan discussed with relatives, welfare proxy and/or carers where appropriate.


BAP guidance (2017) states that there is type I evidence that continuing donepezil may decrease the rate of functional decline in moderate/severe dementia. This  recommendation is based on results of the UK Donepezil and Memantine in Moderate to Severe AD (DOMINO) study (Howard et al 2012), which randomised those on stable donepezil with moderate to severe dementia to continuation donepezil, discontinuation, a change to memantine or adding memantine, clearly showed that continued donepezil treatment (or a switch to memantine or combination therapy) was associated with cognitive and functional benefits over the following 12 months, compared to placebo.

NICE (NG97) 2018 states that AChE inhibitors in people with Alzheimer's disease should not be stopped because of disease severity alone. 

Clinical studies have also shown that interruption of AChE inhibitor therapy for 6 weeks causes a loss of treatment benefit that may not be fully regained when drug treatment is re-initiated (Doody 2001)

Diagnostic and assessment criteria

As per national guidance:

Dementia: assessment, management and support for people living with dementia and their carers. Nice Guideline 97. Published: June 2018 National Institute of Clinical Excellence; London. [online] available from:

Clinical Information

Prescribing information on each of the drugs is available within the:

It is the prescribing clinician’s responsibility to make sure they prescribe according to the most up to date information available, particularly noting the adverse effects, contra-indications and cautions.

Information resources

Information on metal health conditions, treatments and medications for people who use     services, carers and professionals

  • General practitioners, patients and/or carers may also feel free to telephone New Craigs pharmacy for information:

Pharmacy Department, New Craigs Tel: 01463 704663 (Mon to Fri, 8.30am to 5.00pm)


Doody R, Geldmacher D, Gordon B, et al. (2001) Open-label, multicenter, phase III extension study of the safety and efficacy of donepezil in patients with Alzheimer's disease. Arch Neurol58:427–433

Howard R, McShane R, Lindesay J, et al. (2012) Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 366: 893–903.

O’Brien J.T et al. (2017) Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology. Journal of Psychopharmacology. 31 (2), 147-168. [online] available from:

Dementia: assessment, management and support for people living with dementia and their carers. Nice Guideline 97. Published: June 2018 National Institute of Clinical Excellence; London. [online] available from:

Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease. Technology appraisal guidance 217 Published: May 2016 National Institute of Clinical Excellence; London. [online] available from:

Editorial Information

Last reviewed: 31/10/2020

Next review date: 31/10/2023

Author(s): Mental Health Services .

Version: 3.0

Approved By: TAM Subgroup of ADTC

Reviewer name(s): Consultant psychiatrist.

Document Id: TAM244