Second submission on Memantine to the Scottish Medicines Consortium
1. Introduction
When people with Alzheimer’s disease reach the moderate to severe stages of the illness they are becoming increasingly dependent on care from members of their family or care workers. It is no longer a matter of being forgetful, but of needing help with everyday activities such as dressing, washing, feeding and going to the toilet. So dependent are many people with dementia in these stages of the illness that they live in care homes or hospital.
Any treatment that proves to be helpful for those people with dementia is particularly valuable because it makes the caring tasks of family and care workers less onerous.
At these stages of the illness a treatment which stabilises or reduces the rate of deterioration is a worthwhile achievement.
2. Key findings from research
This submission does not repeat the conclusions of the main published studies [1], [2], but points to two key findings.
i) In the M-BEST study, a number of functional variables were used to describe patients’ independence within a wide range from normal functioning to total care dependence. Eight of these variables[3] showed significant improvements over and above the placebo effect, they were:
· ability to stand up
· ability to move
· ability to wash
· ability to take a bath/shower
· ability to dress
· toilet use
· group activities
· hobbies, interests
It is precisely these improvements in activities that make it possible for families and careworkers to look after people with dementia more fulfillingly and at less personal cost to themselves.
ii) Although studies show statistically significant improvements in clinical assessments and activities of daily living for memantine treatment patients over those receiving placebos, the improvements are modest. It could be that they are too modest to justify the use of memantine as a treatment. However, there is one study [4]which reaches the conclusion “Resource utilisation and total health costs were lower in the memantine group than the placebo group. The results suggest that memantine treatment of patients with moderate or severe Alzheimer’s disease is cost saving from a societal perspective.”
This study found, inter alia, that caregivers of patients in the placebo group spent 42 hours per month more on caring tasks and supervision than caregivers of patients receiving memantine. The difference between the two groups increases to 51.5 hours per month when controls for baseline caregiver time, patient gender, caregiver gender, caregiver relationship to patient and baseline residential status are included in the analysis.
This finding shows that the improvements in clinical assessments and activities of daily living, although modest, are real and big enough to have a significant impact on the time devoted by carers to looking after the person with dementia.
3. Reports on the use of memantine
Since the SMC published its recommendations about the use of memantine, Alzheimer Scotland has received a number of reports (see appendix below) about the use of memantine. Though they do not purport to ‘scientific’ evidence, they reinforce the findings of the M-BEST and resource utilisation studies that memantine treated patients show significant improvements in a number of activities of everyday living and that consequently carers spend less time on caring tasks.
4. Conclusion
Alzheimer Scotland urges the SMC to approve the use of memantine for the treatment of people with Alzheimer’s disease because:
i) there is research showing the clinical benefits of treatment
ii) from the perspective of people with the illness and their carers, the improvements, stabilisation or reduction in the rate of deterioration are worthwhile
iii) the benefits to the carers of people with Alzheimer’s disease are substantial
iv) the introduction of memantine as a treatment for people with moderate to severe Alzheimer’s disease will be an important breakthrough that will give hope at a particularly distressing stage of the illness.
Postscript
On 24 September 2003, the US Food & Drug Administration (FDA) received recommendations from its Peripheral & Central Nervous System Drugs Advisory Committee on the use of memantine. The committee recommended approval of memantine for the treatment of moderate to severe Alzheimer’s disease.
The FDA is under no obligation to accept guidance from its advisory committees, though the agency often follows their recommendations. An FDA advisory committee provides independent, expert scientific and medical advice to the FDA on safety, effectiveness and appropriate use of products under its jurisdiction.
Appendix
Reports on the use of memantine
“Since her release from hospital nine months ago, she has been on this drug. Her ability to lead a fuller and more normal way of life has improved very substantially. The gains have been remarkable.
Before my wife’s release from hospital, our social work department was talking about a care plan which costed out at approximately £240,000. Due to my wife’s much improved condition, we are running on a much-modified plan which costs the government something under £100,000.”
Carer, Argyll and Clyde, August 2003
“The results are very pleasing. Her sleeping, eating and toileting have improved and her mini mental state test scored also improved.
On the downside, it would seem that she now tries to do more things and becomes frustrated when she cannot complete them.
The general effect is of having the clock turned back.
If this is sustained, then full time care can be postponed. Both the washing machine and myself are giving sighs of relief.”
Carer, Newsletter of the Alzheimer’s Society, February 2003
“Carer reported marked ‘functional’ changes which I can corroborate, ie improved communication and language, increased animation and brighter mood. Also the patient had been quite agitated and became more settled.”
Community psychiatric nurse, Highland, August 2003
“Two patients were prescribed Ebixa by their GP. Both were monitored carefully and fully reviewed after 12 weeks treatment and in both cases the conclusion was that they had responded positively.
The first gentleman became more alert. Improvement was not dramatic, but it was important. Carers used to have a real problem assisting this gentleman in going to the toilet since he did not recognise a bathroom or what it was for and what he should do when he got there. After treatment with Ebixa he began to recognise bathrooms again and initiate correct actions when he went into a bathroom. A carer from Crossroads, who used to take the gentleman out to give his wife respite, also reported the gentleman taking greater interest in his surroundings and hence getting more enjoyment, for example he spent time looking around the cathedral and reading and taking an interest in everything he saw instead of his previous disengagement and disinterest.
The lady who was treated had not been able to tolerate treatment attempted earlier with cholinesterase inhibitors. She had no problems with Ebixa. She improved in her ability to carry out simple tasks like managing in the toilet more independently and washing and dressing. Improved abilities were accompanied by reduced frustration and the lady became less angry and hostile towards her family carers”.
Community Dementia Nurse, September 2003
“My seventy five year old sister commenced Ebixa in December 2002 and as caring sisters we felt she was less agitated than previously. She was more settled in herself and continues to be prescribed this medication.”
Carer
Ross-shire, September 2003
“I am relieved that my wife will be able to continue to receive this drug as I feel it has had a tremendous effect on her. She was diagnosed with dementia 14 years ago, and last year things were at a really low ebb. Her weight was down to five stones at one point. Thanks to our consultant psychiatrist prescribing this drug, along with the excellent help we had from the Bruce Medical Centre and Alzheimer Scotland, there has been a marvellous difference”.
Carer, Lanarkshire, August 2003
“The family are most positive about the result. Although there is no improvement in the lady’s memory, they claim she is much less tired and agitated than she was before taking the drug. This lady had been previously prescribed Aricept some five years ago but the drug was stopped after two months due to an adverse reaction. The main carer is very badly physically disabled and uses a wheelchair at all times. Before this new drug, the outlook for his wife was very bleak and she would have probably ended up in long term care sooner rather than later. The hope now is that she can stay at home for an extended period”.
Service Manager, Inverclyde, May 2003
“I have identified four people in my carers’ group that have relatives on Ebixa, three have reported improvements in continence and communication skills, one has been taken off as ‘it put him all wrong’.Carer Resource Worker, Highland, May 2003
[1] Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobias H.J. for the Memantine Study Group. (2003) A randomised, placebo-controlled study of memantine, an uncompetitive NMDA antagonist, in patients with moderate to severe Alzheimer's disease. New England Journal of Medicine. 348, 1333-41.
[2] Winblad B., Poritis N. (1999) Memantine in severe dementia: Results of the M-Best Study. International Journal of Geriatric. Psychiatry 14, 135 -146.
[3]Winblad, B Jelic, V. 2003 Treating the full spectrum of dementia with memantine. International Journal of Geriatric Psychiatry 18:541 - 546.
[4] Wimo A, Winblad B, Stoffler A, Wirth YM and Mobias H.J. (2003) Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer's disease. Pharmacoeconomics 21(5): 1: 1170-7690.
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