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Brief Summary

GUIDELINE TITLE

(1) Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (2) 2007 addendum.

BIBLIOGRAPHIC SOURCE(S)

  • National Institute for Health and Clinical Excellence (NICE). Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended). London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Sep. 62 p. (Technology appraisal guidance; no. 111).

GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previously released version: Alzheimer's disease (mild to moderate) - donepezil, rivastigmine and galantamine. NICE technology appraisal guidance 19. 2001 Jan.

** REGULATORY ALERT **

FDA WARNING/REGULATORY ALERT

BRIEF SUMMARY CONTENT

 ** REGULATORY ALERT **
 RECOMMENDATIONS
 EVIDENCE SUPPORTING THE RECOMMENDATIONS
 IDENTIFYING INFORMATION AND AVAILABILITY
 DISCLAIMER

 Go to the Complete Summary

RECOMMENDATIONS

MAJOR RECOMMENDATIONS

Note from the National Guideline Clearinghouse (NGC) and the National Institute for Health and Clinical Excellence (NICE): Following the outcome of a judicial review in August 2007, NICE has amended and reissued this guidance. The amended guidance clarifies the steps healthcare professional should take when assessing whether Alzheimer's disease is of moderate severity and highlights that clinicians should be mindful of the need to secure equality of access to treatment.

The amendments include new text that specifically addresses assessments, using the Mini Mental State Examination (MMSE) for patients:

  • 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

Guidance

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 people 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 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.

CLINICAL ALGORITHM(S)

None provided

EVIDENCE SUPPORTING THE RECOMMENDATIONS

TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are based on randomized, controlled trials, systematic review, and published economic evaluations.

IDENTIFYING INFORMATION AND AVAILABILITY

BIBLIOGRAPHIC SOURCE(S)

  • National Institute for Health and Clinical Excellence (NICE). Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended). London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Sep. 62 p. (Technology appraisal guidance; no. 111).

ADAPTATION

Not applicable: The guideline was not adapted from another source.

DATE RELEASED

2001 Jan (revised 2006 Nov; addendum released 2007 Sep)

GUIDELINE DEVELOPER(S)

National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]

SOURCE(S) OF FUNDING

National Institute for Health and Clinical Excellence (NICE)

GUIDELINE COMMITTEE

Appraisal Committee

COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

Committee Members: Dr Jane Adam, Radiologist, St George's Hospital, London; Professor A E Ades, MRC Senior Scientist, MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol; Dr Tom Aslan, General Practitioner, Stockwell, London; Professor David Barnett (Vice Chair) Professor of Clinical Pharmacology, University of Leicester; Mrs Elizabeth Brain, Lay Member; Dr Karl Claxton, Health Economist, University of York; Dr Richard Cookson, Senior Lecturer in Health Economics, School of Medicine Health Policy and Practice, University of East Anglia; Mrs Fiona Duncan, Clinical Nurse Specialist, Anaesthetic Department, Blackpool Victoria Hospital, Blackpool; Professor Christopher Eccleston, Director Pain Management Unit, University of Bath; Dr Paul Ewings, Statistician, Taunton & Somerset NHS Trust, Taunton; Professor Terry Feest, Professor of Clinical Nephrology, Southmead Hospital; Ms Alison Forbes, Lay Member; Professor John Geddes, Professor of Epidemiological Psychiatry, University of Oxford; Mr John Goulston, Director of Finance, Barts and the London NHS Trust; Ms Linda Hands, Consultant Surgeon, John Radcliffe Hospital, Oxford; Dr Elizabeth Haxby, Lead Clinician in Clinical Risk Management, Royal Brompton Hospital; Dr Rowan Hillson, Consultant Physician, Diabeticare, The Hillingdon Hospital; Dr Catherine Jackson, Clinical Senior Lecturer in Primary Care Medicine, Alyth Health Centre, Angus, Scotland; Dr Simon Mitchell, Consultant Neonatal Paediatrician, St Mary's Hospital, Manchester; Ms Judith Paget, Chief Executive, Caerphilly Local Health Board, Wales; Dr Katherine Payne, Health Economist, The North West Genetics Knowledge Park, The University of Manchester; Dr Ann Richardson, Lay Member; Professor Philip Routledge, Professor of Clinical Pharmacology, College of Medicine, University of Wales, Cardiff; Dr Stephen Saltissi, Consultant Cardiologist, Royal Liverpool University Hospital; Mr Mike Spencer, General Manager, Clinical Support Services, Cardiff and Vale NHS Trust; Dr Debbie Stephenson, Head of HTA Strategy, Eli Lilly and Company; Professor Andrew Stevens (Chair) Professor of Public Health, University of Birmingham; Dr Cathryn Thomas, General Practitioner, & Associate Professor, Department of Primary Care & General Practice, University of Birmingham; Dr Norman Vetter, Reader, Department of Epidemiology, Statistics and Public Health, College of Medicine, University of Wales, Cardiff; Professor Mary Watkins, Professor of Nursing, University of Plymouth; Dr Paul Watson, Medical Director, Essex Strategic Health Authorit; Dr David Winfield, Consultant Haematologist, Royal Hallamshire Hospital, Sheffield

FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal.

GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previously released version: Alzheimer's disease (mild to moderate) - donepezil, rivastigmine and galantamine. NICE technology appraisal guidance 19. 2001 Jan.

GUIDELINE AVAILABILITY

AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

Print copies: Available from the National Health Service (NHS) Response Line 0870 1555 455. ref: N1142. 11 Strand, London, WC2N 5HR.

PATIENT RESOURCES

The following is available:

  • Donepezil, galantamine, rivastigmine and memantine for Alzheimer's disease. Understanding NICE guidance (amended). Information for people who use NHS services. London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Sep. 4 p. (Technology appraisal 111).

Electronic copies: Available in Portable Document Format (PDF) from the National Institute for Health and Clinical Excellence (NICE) Web site.

Print copies: Available from the NHS Response Line 0870 1555 455. ref: N1143. 11 Strand, London, WC2N 5HR.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC STATUS

COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

DISCLAIMER

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