Alzheimer's disease - donepezil, galantamine, rivastigmine (review) and memantine

1. Guidance

NOTE: This technology appraisal was first issued in November 2006. It was amended in September 2007. This second amendment is effective from August 2009

This guidance applies to donepezil, galantamine, rivastigmine and memantine within the marketing authorisations held for each drug at the time of this appraisal; that is:

• donepezil, galantamine, rivastigmine for mild to moderately severe Alzheimer’s disease
• memantine for moderately severe to severe Alzheimer’s disease.

The benefits of these drugs for patients with other forms of dementia (for example, vascular dementia or dementia with Lewy bodies) have not been assessed in this guidance.

1.1. The three acetylcholinesterase inhibitors donepezil, galantamine and rivastigmine are recommended as options in the management of patients with Alzheimer’s disease of moderate severity only (that is, subject to section 1.2 below, those with a Mini Mental State Examination [MMSE] score of between 10 and 20 points), and under the following conditions:

• Only specialists in the care of patients with dementia (that is, psychiatrists including those specialising in learning disability, neurologists, and physicians specialising in the care of the elderly) should initiate treatment. Carers’ views on the patient’s condition at baseline should be sought.
• Patients who continue on the drug should be reviewed every 6 months by MMSE score and global, functional and behavioural assessment. Carers’ views on the patient’s condition at follow-up should be sought. The drug should only be continued while the patient’s MMSE score remains at or above 10 points (subject to section 1.2 below) and their global, functional and behavioural condition remains at a level where the drug is considered to be having a worthwhile effect. Any review involving MMSE assessment should be undertaken by an appropriate specialist team, unless there are locally agreed protocols for shared care.

When using the MMSE to diagnose moderate Alzheimer’s disease, clinicians should be mindful of the need to secure equality of access to treatment for patients from different ethnic groups (in particular those from different cultural backgrounds) and patients with disabilities.

1.2. In determining whether a patient has Alzheimer’s disease of moderate severity for the purposes of section 1.1 above, healthcare professionals should not rely, or rely solely, upon the patient’s MMSE score in circumstances where it would be inappropriate to do so. These are:

• where the MMSE is not, or is not by itself, a clinically appropriate tool for assessing the severity of that patient’s dementia because of the patient’s learning or other disabilities (for example, sensory impairments) or linguistic or other communication difficulties or
• where it is not possible to apply the MMSE in a language in which the patient is sufficiently fluent for it to be an appropriate tool for assessing the severity of dementia, or there are similarly exceptional reasons why use of the MMSE, or use of the MMSE by itself, would be an inappropriate tool for assessing the severity of dementia in that individual patient’s case.

In such cases healthcare professionals should determine whether the patient has Alzheimer’s disease of moderate severity by making use of another appropriate method of assessment. For the avoidance of any doubt, the acetylcholinesterase inhibitors are recommended as options in the management of people assessed on this basis as having Alzheimer’s disease of moderate severity.

The same approach should apply in determining for the purposes of section 1.1 above, and in the context of a decision whether to continue the use of the drug, whether the severity of the patient’s dementia has increased to a level which in the general population of Alzheimer’s disease patients would be marked by an MMSE score below 10 points.

1.3. When the decision has been made to prescribe an acetylcholinesterase inhibitor, it is recommended that therapy should be initiated with a drug with the lowest acquisition cost (taking into account required daily dose and the price per dose once shared care has started). However, an alternative acetylcholinesterase inhibitor could be prescribed where it is considered appropriate having regard to adverse event profile, expectations around concordance, medical comorbidity, possibility of drug interactions and dosing profiles.

1.4. Memantine is not recommended as a treatment option for patients with moderately severe to severe Alzheimer’s disease except as part of well-designed clinical studies.

1.5. Patients with mild Alzheimer’s disease who are currently receiving donepezil, galantamine or rivastigmine, and patients with moderately severe to severe Alzheimer’s disease currently receiving memantine, whether as routine therapy or as part of a clinical trial, may be continued on therapy (including after the conclusion of a clinical trial) until they, their carers and/or specialist consider it appropriate to stop.