Drugs for dementia

Please give feedback on this information

Copyright note for Mind factsheets: Both individuals and organisations are welcome to print and photocopy any complete factsheet from the 'Information' section of Mind's website. Organisations are free to distribute them to service users and colleagues, but must ensure they always use the latest version of the factsheet, as available on the website, at the time of distribution.

Introduction
Which drugs are used?
NICE Guidelines
How do the drugs work?
What are the cautions and side effects associated with these drugs?
      Donepezil (Aricept)
     Galantamine (Reminyl and Reminyl XL)
     Rivastigmine (Exelon)
     Memantine (Ebixa)
References

Introduction

This factsheet is about the drugs which may be helpful for Alzheimer’s disease, dementia with Lewy bodies, and vascular dementia. It summarises the current position of NICE guidelines on the use of these drugs, and gives information about the cautions for their use and possible side effects.

Which drugs are used?

The first drug for dementia was licensed in the UK in 1997.

There are now four drugs licensed for the treatment of dementia: donepezil (trade name Aricept, 1997), galantamine (Reminyl, 2000), rivastigmine (Exelon, 2003), and memantine (Ebixa, 2002).

Donepezil, galantamine and rivastigmine are licensed for the treatment of mild to moderate dementia. They are not thought to be effective in people with more severe, late stage disease, although a study published in the Lancet in April 2006 suggested that donepezil was effective in people with severe disease. Memantine is licensed for the treatment of moderate to severe Alzheimer’s disease.

Back to top

NICE Guidelines

In January 2001, the National Institute for Health and Clinical Excellence (NICE) issued guidance on the use of donepezil, galantaine and rivastigmine for dementia. This guidance recommends that donepezil, galantamine and rivastigmine should be available for people whose mini mental-state examination (MMSE, the standard assessment tool for dementia) score is above 12 points, under the following conditions:

• Alzheimer’s disease must be diagnosed in a specialist clinic, which should also assess all aspects of functioning, including the likelihood that the person will take medication.
• The treatment should be started by a specialist, but may be continued by a GP under a shared care protocol.
• The carer’s views about the condition should be sought before and during drug treatment.
• The patient should be assessed two to four months after the maintenance dose is established, and the drug should be continued only if there has been improvement in the MMSE or no deterioration, and behavioural or functional assessment has improved.
• Assessment should be repeated every six months and the drug should normally be continued only if the MMSE remains above 12 points and treatment is considered to be having a worthwhile effect on the person’s overall state.

The drugs should be stopped if the person does not seem to be responding. Many specialists repeat the assessment four to six weeks after stopping the drug and may start it again if there has been significant deterioration during this short period.

This NICE guidance was reviewed in 2005 with a suggestion that the efficacy of these drugs was not sufficiently established to authorise their continued use by the NHS, although people already taking the drugs could remain on them. This caused an outcry among service users, carers, and their representatives, all of whom clearly felt that the medications had made a significant and positive difference to the experience of living with dementia, and had delayed the progression of the disease in many cases.

NICE asked the drug companies to look for evidence that the drugs are effective in certain groups of people. The results showed that donepezil, galantamine and rivastigmine were effective in people with moderate Alzheimer’s disease, and that these three drugs should be considered for treating this group, defined as those with a MMSE score of 10-20 points. This would exclude people in the earlier stages of the disease.

The new guideline, which covers all aspects of the care and treatment of people with dementia, is expected to be completed by December 2006. When it is published, it will apply only to people newly diagnosed with dementia, while people already taking the drugs should continue to do so.

In the case of memantine, a drug which works in a different way from the other three, and is licensed for the treatment of moderate to severe dementia, NICE has said that there is not sufficient evidence to justify its use, and it should be used only as part of clinical research studies.

Back to top

How do the drugs work?

Donepezil, galantamine and rivastigmine work by increasing the amount of the neurotransmitter acetylcholine in the brain. The levels of this neurotransmitter gradually diminish in Alzheimer’s disease, producing some of the symptoms. The drugs boost the levels of the neurotransmitter and slow the rate of decline associated with the disease.

Memantine interferes with the action of glutamate, a different neurotransmitter.

Back to top

What are the cautions and side effects associated with these drugs?

Donepezil (Aricept)

Cautions
Donepezil should not be used in pregnancy or while breastfeeding. It should be used with caution in people with certain heart problems or susceptible to stomach ulcers; people with asthma or lung disease; people with Parkinson’s symptoms; and those with liver disease.

Side effects
Feeling or being sick, loss of appetite, diarrhoea, tiredness, sleep disturbance, headache, dizziness, fainting, psychiatric disturbances, muscle cramps, urinary incontinence, rash, itching. Less commonly: slow heartbeat, fits, stomach and duodenal ulcers, internal bleeding, heart disorders, liver problems. Difficulty emptying the bladder may occur.

Dose
Donepezil comes in the form of tablets. The usual dose is 5mg/day, with a maximum of 10mg/day.

Back to top

Galantamine (Reminyl and Reminyl XL)

Cautions
Galantamine should not be used by patients with severe liver disease, or while breastfeeding. It should be used with caution in people with certain heart problems; those with disturbed salt balance; those susceptible to stomach ulcers; people with asthma or lung disease including infections; those with urinary retention and gut obstruction, liver disease, and in pregnancy.

Side effects
Feeling or being sick, diarrhoea, stomach ache, indigestion, fainting, stuffy nose, sleep disturbances, dizziness, confusion, depression, headache, tiredness, loss of appetite, tremor, fever, weight loss. Less commonly: irregular heart beat, palpitations, heart attack, damage to blood vessels in the brain, tingling sensations, tinnitus (ringing in the ears), leg cramps. Rarely: slow heartbeat, fits, hallucinations, agitation, aggression, dehydration, low blood potassium, and rash. Very rarely: internal bleeding, difficulty swallowing, low blood pressure, worsening of Parkinson’s disease, sweating.

Dose
Galantamine comes as tablets and as a liquid. The usual dose is 4mg twice a day for four weeks, with a maintenance dose of 8-12mg twice a day.
The modified release form (Reminyl XL) comes in capsules, given at 8mg once a day for the first four weeks, and 16-24mg once a day as a maintenance dose.

Back to top

Rivastigmine (Exelon)

Cautions
Rivastigmine should not be used while breastfeeding. It should be used with caution in people with kidney disease, some heart conditions, those at risk of developing stomach ulcers, those with asthma or lung disease, fits, problems emptying the bladder, and in pregnancy. It may worsen the symptoms of Parkinson’s disease. Body weight should be checked regularly.

Side effects
Feeling and being sick, diarrhoea, indigestion, loss of appetite, stomach ache, dizziness, headache, sleepiness, tremor, loss of energy or strength, feeling unwell, agitation, confusion, sweating. Less commonly: fainting, depression, lack of sleep. Rarely: stomach or duodenal ulcers, internal bleeding, pancreatitis, angina (heart pain), irregular heart beat, slow heart beat, high blood pressure, fits, hallucinations, urine infection, rash. Side effects affecting the gut are more common in women.

Dose
Rivastigmine comes as capsules and as a liquid. The starting dose is 1.5mg twice a day, increasing in steps of 1.5mg twice a day at intervals of at least 2 weeks according to response. The usual dose is 3-6mg twice a day. The maximum is 6mg twice a day.

Back to top

Memantine (Ebixa)

Cautions
Memantine should not be used while breastfeeding. It should be used with caution in people with a history of fits, those with kidney disease, and in pregnancy.

Side effects
Constipation, headache, dizziness, sleepiness. Less commonly: being sick, confusion, tiredness, hallucinations, abnormal gait. Very rarely: fits.

Dose
Memantine comes as tablets and as oral drops. The starting dose is 5mg in the morning, increased in steps of 5mg each week up to a maximum of 10mg twice a day.

Back to top

References

British National Formulary (BNF) 51, March 2006.
Mayor, S, 2006, ‘NICE recommends drugs for moderate Alzheimer’s disease’, BMJ, vol 332, 28 January, p195.
National Institute for Health and Clinical Excellence (NICE) website, www.nice.org.uk
Winblad, B. et al, 2006, ‘Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study’, The Lancet, vol 367, 1 April, pp1057-1065.

This factsheet was written by Katherine Darton, Mind Information Unit, June 2006.