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Introduction

NICE recently issued its Final Appraisal Determination (FAD) on the prescribing of cholinesterase inhibitors and memantine for the treatment of Alzheimer’s disease. These have been widely criticised, and were appealed by several parties including the Royal College of Psychiatrists, British Geriatrics Society and Royal College of Nursing. NICE have since indicated that none of the objections raised at the appeal have been upheld. This position statement was prepared on behalf of the above professional bodies, whose clinicians NICE consider specialist enough to initiate these medications. These bodies represent the overwhelming majority of prescribers who start treatment. It should be noted that these medications are still licensed for doctors to prescribe. The paper aims to support clinicians in preparing to meet their duties and responsibilities as doctors while implementing this flawed guidance, and will also help healthcare organisations avoid unlawful discrimination.

1. Duties and responsibilities of individual clinicians to apply professional standards in their implementation of NICE guidance

GMC: duties of a doctor

The first duty of a doctor as described by the GMC in “Good Medical Care” 1 is to their patient:

“ In particular as a doctor you must: make the care of your patient your first concern”

In considering GMC guidance and their continued registration with the GMC, doctors should remember that they must make the care of their patient their first concern. Whilst doctors have to be mindful of is sue s of equity and cost-effectiveness, they should also consider an individual patient's needs and the circumstances that might warrant a departure from the general policy of NICE guidance.

1.2 NICE: responsibility of healthcare professionals

NICE Health Technology Appraisal guidance is is sue d with the rider that:
“This guidance represents the view of the Institute, which was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. The guidance does not, however, override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.”

NICE clearly therefore does not expect its guidance to override a clinician’s duty as a doctor.

2. NICE guidance on the cholinesterase inhibitors ( Donepezil, galantamine, rivastigmine)

NICE’s FAD on the cholinesterase inhibitors suggests the use of a patient’s Mini-Mental State Examination score to determine access to medication. However, this is sometimes inappropriate, and it is a clinician’s duty as described by the GMC, and their responsibility as described by NICE, to prioritise the clinical needs of the individual patient. Clinicians are therefore required to use their professional judgement in the use of the MMSE score in implementing NICE guidance, and healthcare commissioners and provider organisations should not over-ride these professional considerations.

2.1 The importance of interpreting MMSE score for each individual patient

The MMSE was designed as a screening tool for dementia, but has subsequently been used to measure progression of disease and response to anti-dementia medication. While these uses may be justifiable when applied to populations, there are serious difficulties when this measure is applied to an individual to assess their response to treatment or to use an individual’s performance to define eligibility to treatment, due to day-to-day variability in score, and other individual circumstances that affect scoring.

As part of a large multi-centre study designed to develop standardised methods for the assessment of Alzheimer’s Disease 2, 331 patients with Alzheimer’s disease had repeat MMSE testing at a one month interval. Changes in score ranged from an increase of 7 points to a decrease of 8 points, with an average change of -0.5 (SD 2.8). 95% of patients’ retest scores were within 6 points of their original scores.

The MMSE is largely language based and is influenced by educational level and sensory abilities, so it is well known that MMSE score will be relatively low in people with dysphasia or sensory impairments, people for whom English is not a first language, and people with low IQ, and relatively high for people with high educational background. As recognised in the draft NICE guideline for dementia, the MMSE is inappropriate for people with learning disabilities, and alternatives are available.

2.2 Recommendations on prescribing of cholinesterase inhibitors

In order to allow doctors to meet their responsibilities under NICE guidance and their duties as doctors under GMC guidance, it is recommended that:

2.2.1. Clinicians should interpret the MMSE score in the light of the individual patient’s circumstances. This will include an acceptance that there is day-to-day variability in MMSE score, and aspects of sensory ability language and educational performance are relevant to the interpretation of a person’s MMSE score.

2.2.2. Any audit of the use of cholinesterase inhibitor prescribing should allow exceptions to compliance with the MMSE range of 10-20 if there is an appropriate documented reason for this (reasons might include unexpected variability in MMSE score, sensory impairment, language or educational is sue s, and other particular circumstances of the individual patient).

2.2.3 Clinicians, service providers and commissioners should be fully aware that there may be additional recommendations contained within the Joint NICE/SCIE Dementia Guideline regarding the circumstances in which cholinesterase inhibitors should be prescribed to those with AD whose MMSE lies outside the usual treatment range of 10-20.

3. NICE guidance on memantine

3.1 The NICE Final Appraisal Determination suggests that “Memantine is not recommended as a treatment option for people with Alzheimer’s disease except as part of well designed clinical studies.” However, there are compelling reasons why doctors should continue to be allowed to prescribe memantine in defined circumstances.

Memantine reduces caregiver time and helps behavioural symptoms such as agitation, aggression and psychosis in people with Alzheimer’s disease. These behavioural symptoms cause carer strain and lead to increased care requirements and institutionalization though are often short-lived. Alternative medications such as antipsychotics and sedatives are often more expensive, have to be prescribed off-license, and may cause strokes and falls with consequent fractures. Thus the use of memantine may improve outcomes for people with Alzheimer’s disease, reduce carer burden, lead to more legitimate prescribing, reduce the costs of alternative medication, and reduce the need for specialist and continuing care.

3.2 Recommendations on prescribing of memantine

In order to allow doctors to meet their responsibilities under NICE guidance and their duties as doctors under GMC guidance, it is recommended that:

3.2.1. Memantine is considered as an option in the management of people with moderate to severe Alzheimer’s disease (normally MMSE 20 and below though see advice above with regard to interpretation of MMSE scores)  in certain defined circumstances. These might include:

a) People who have at least moderate behavioural disturbance, where non-pharmacological interventions are ineffective or inappropriate, and where the severity of risk does not require urgent sedation or antipsychotic medication.

b) People for whom cholinesterase inhibitors are inappropriate though where they would otherwise be indicated (for example where medically contraindicated or not tolerated).

3.2.2 Audit standards should require that people prescribed memantine have documented behavioural problems which needed pharmacological treatment, documented review within 3 months to establish benefit, and ongoing review 6 monthly with a trial withdrawal unless there are documented reasons why this was not appropriate (perhaps based on level of risk).

References

1. Good Medical Practice (Third edition) 2001. General Medical Council, London .

2. Variability in annual Mini-Mental State Examination score in patients with probable Alzheimer’s disease: A clinical perspective of data from the Consortium to Establish a Registry for Alzheimer’s Disease. Clark CM, Sheppard L, Fillenbaum GG, Galasko D, Morris JC, Koss E et al. Archives of Neurology 1999: 56 (july); 857-862.