There’s no drug to cure dementia yet, but it’s often possible to relieve some symptoms. Learn more about the main drug treatments for Alzheimer’s disease. There are no drug treatments that can cure Alzheimer’s disease or any other common type of dementia. However, medicines have been developed for Alzheimer’s disease that can temporarily alleviate symptoms, or slow down their progression, in some people. Drug treatment for Alzheimer’s disease is important, but the benefits are small, and drugs should only be one part of a person’s overall care. Non-drug treatments, activities and support are just as important in helping someone to live well with Alzheimer’s disease.

What are the main drugs used to treat Alzheimer’s disease?

Many drugs have at least two names. The generic name identifies the substance, and the brand name varies depending on the company that manufactures it. For example, a familiar painkiller has the generic name paracetamol and is manufactured under brand names such as Panadol and Calpol, among others. Occasionally, a drug with a very well-known generic name (such as paracetamol) will also be manufactured and sold using just this name. There are two types of medication used to treat Alzheimer’s disease, which work in different ways.

Acetylcholinesterase inhibitors (or ‘cholinesterase’ inhibitors) The generic names for the cholinesterase inhibitors are donepezil, rivastigmine and galantamine:

• Donepezil was originally patented as the brand name Aricept, but is more widely available now as just generic donepezil.
• Rivastigmine was patented as Exelon and is now also available as other brands, as well as generic rivastigmine.
• Galantamine was patented as Reminyl and is now also available as generic galantamine and the brands Reminyl XL, Acumor XL, Galsya XL and Gatalin XL

NMDA receptor antagonists
The NMDA receptor antagonist is memantine. It was originally patented as Ebixa and is now also available as generic memantine.
Other UK brand names for memantine include Maruxa and Nemdatine

Here we explain the effects, within the brain and its nerve cells, of different types of cholinesterase inhibitors.

Donepezil, rivastigmine and galantamine

In the brain of a person with Alzheimer’s disease, there are lower levels of a chemical called acetylcholine. Acetylcholine helps to send messages between certain nerve cells. In Alzheimer’s, there is also a loss of the nerve cells that use acetylcholine. Falling acetylcholine levels and progressive loss of these nerve cells are linked to worsening symptoms.

Donepezil, rivastigmine and galantamine all prevent an enzyme called acetylcholinesterase from breaking down acetylcholine in the brain. As a result, an increased concentration of acetylcholine leads to increased communication between nerve cells. This may temporarily alleviate or stabilise some symptoms of Alzheimer’s disease. All three cholinesterase inhibitors work in a similar way, but one might suit a certain individual better than another, particularly in terms of side effects experienced.

Usage guidance

Guidance on the use of drugs in the NHS is issued by the National Institute for Health and Care Excellence (NICE). NICE reviews drugs and decides whether they represent good enough value for money to be available as part of NHS treatment. Drugs considered by NICE will also have been through the UK or European licensing process for new medicines. This means the medicine has been tested and met rigorous standards of safety, quality and effectiveness. The licence will be granted for treatment of a particular health condition. For the cholinesterase inhibitors, the NICE guidance (2011) suggests that the cheapest drug (currently donepezil) should generally be tried first.

Memantine

The action of memantine is different from that of donepezil, rivastigmine and galantamine. Glutamate is another chemical that helps to send messages between nerve cells. Glutamate is released in excessive amounts when brain cells are damaged by Alzheimer’s disease. This causes the brain cells to be damaged further. Memantine protects brain cells by blocking the effects of excess glutamate.

Are drugs effective for everyone with Alzheimer’s disease? We explain the benefits, how addictive the drugs are, and what the side effects might be.

Donepezil, rivastigmine and galantamine

The guidance from NICE (2011) recommends that donepezil, rivastigmine or galantamine is offered as part of NHS care for people with mild-to-moderate Alzheimer’s disease. There is good evidence (strongest for donepezil) that these cholinesterase inhibitors also help people with more severe Alzheimer’s disease.

Between 40 and 70 per cent of people with Alzheimer’s disease benefit from taking a cholinesterase inhibitor. In cases where the treatment shows benefit, symptoms improve temporarily (for between six and 12 months in most cases) and then gradually worsen over the following months. People taking a cholinesterase inhibitor can experience

• reduced anxiety
• improvements in motivation, memory and concentration
• improved ability to continue daily activities.

It is not clear whether the cholinesterase inhibitors also bring benefits for behavioural changes such as agitation or aggression. Trials in this area have given mixed results.

Memantine

The NICE guidance (2011) recommends use of memantine as part of NHS care for severe Alzheimer’s disease. NICE also recommends memantine for people with moderate Alzheimer’s disease who cannot take the cholinesterase inhibitor drugs. This is usually because of side effects. Memantine is licensed for the treatment of moderate-to-severe Alzheimer’s disease. In people in the middle and later stages of the disease, it can slow down the progression of symptoms, including disorientation and difficulties carrying out daily activities. There is some evidence that memantine may also help with symptoms such as delusions, aggression and agitation.

Are there any side effects?

Generally, cholinesterase inhibitors and memantine can be taken without too many side effects. Not everyone experiences the same side effects, or has them for the same length of time (if they have them at all). The most frequent side effects of donepezil, rivastigmine and galantamine are loss of appetite, nausea, vomiting and diarrhoea. Other side effects include muscle cramps, headaches, dizziness, fatigue and insomnia. Side effects can be less likely for people who start treatment by taking the lower prescribed dose for at least a month.

The side effects of memantine are less common and less severe than for the cholinesterase inhibitors. They include dizziness, headaches, tiredness, raised blood pressure and constipation. It is important to discuss any side effects with the GP and/or the pharmacist. None of these drugs are addictive.

Learn about the process of having Alzheimer’s disease drugs prescribed by specialists in dementia care.

Who would prescribe the drugs?

NICE guidance (2011) states that, in the first instance, Alzheimer’s disease drugs can only be prescribed by a specialist in dementia care. This will often be a consultant old-age psychiatrist, geriatrician or neurologist. A GP will generally refer a person with suspected dementia to a memory service for a specialist assessment. A consultant-led team at the clinic will carry out a series of tests to determine whether the person has dementia and, if so, which type. If the diagnosis is Alzheimer’s disease, the consultant will offer the drugs and write the first prescription. In some parts of the country, arrangements allow for the consultant to write to the GP to ask them to start prescribing.

What follows after the initial prescription?

Once the person has started on the drugs and is stable at the optimum dose, the specialist will usually ask the GP to take over routine prescribing. The person will then generally have regular reviews of how well their medication is working, either with a specialist at the memory clinic or with the GP. This divided responsibility between the consultant and GP is sometimes called shared care prescribing.

We explore the evidence behind the effectiveness of Alzheimer’s disease drugs as treatment for people that are living with other types of dementia.

What does the research say?

The cholinesterase inhibitors were developed specifically to treat Alzheimer’s disease. There has been relatively little research into whether they, or memantine,  are helpful for people with other types of dementia.

Drugs for dementia with Lewy bodies, and Parkinson’s disease dementia

There is evidence that the cholinesterase inhibitors are effective in people with dementia with Lewy bodies, and dementia due to Parkinson’s disease. Rivastigmine is licensed for Parkinson’s disease dementia. Acetylcholine levels are often even lower in people with dementia with Lewy bodies than in those with Alzheimer’s disease. NICE guidelines recommend that a cholinesterase inhibitor is offered to a person with dementia with Lewy bodies or Parkinson’s disease dementia if they have distressing symptoms, such as hallucinations, or challenging behaviours, such as agitation or aggression. For memantine, one trial showed benefits for people with dementia with Lewy bodies and Parkinson’s disease dementia, but there is not enough evidence to draw any firm conclusions.

Drugs for vascular dementia

Several trials have looked at the treatment of vascular dementia with a cholinesterase inhibitor or memantine. The benefits for either are very small, if any at all. These benefits are seen mainly for mental abilities of people with a combination of both Alzheimer’s disease and vascular dementia (known as mixed dementia). NICE guidelines recommend cholinesterase inhibitors for treatment of mixed dementia when Alzheimer’s is the main cause, but not for the treatment of pure vascular dementia.

Drugs for frontotemporal dementia

From the few trials carried out, there is no good evidence that the cholinesterase inhibitors or memantine are of benefit for people with frontotemporal dementia, including Pick’s disease. In some people they may make symptoms worse. These drugs are not licensed for frontotemporal dementia and will not generally be prescribed for it.

There is currently no cure for vascular dementia: the brain damage that causes it cannot be reversed. However, there is a lot that can be done to enable someone to live well with the condition. This will involve drug and non-drug treatment, support and activities. The person should have a chance to talk to a health or social care professional about their dementia diagnosis. This could be a psychiatrist or mental health nurse, a clinical psychologist, occupational therapist or GP. Information on what support is available and where to go for further advice is vital in helping someone to stay physically and mentally well.

Control of cardiovascular disease

If the underlying cardiovascular diseases that have caused vascular dementia can be controlled, it may be possible to slow down the progression of the dementia. For example, after someone has had a stroke or TIA, treatment of high blood pressure can reduce the risk of further stroke and dementia. For stroke-related dementia in particular, with treatment there may be long periods when the symptoms don’t get significantly worse. In most cases, a person with vascular dementia will already be on medications to treat the underlying diseases. These include tablets to reduce blood pressure, prevent blood clots and lower cholesterol. If the person has a diagnosed heart condition or diabetes they will also be taking medicines for these. It is important that the person continues to take any medications and attends regular check-ups as recommended by a doctor.

Someone with vascular dementia will also be advised to adopt a healthy lifestyle, particularly to take regular physical exercise and, if they are a smoker, to quit. They should try to eat a diet with plenty of fruit, vegetables and oily fish but not too much fat or salt. Maintaining a healthy weight and keeping to recommended levels of alcohol will also help. The GP should be able to offer advice in all these areas.

Other treatment and support

Supporting a person with vascular dementia to live well includes treatment for symptoms, support to cope with lost abilities, and help to keep up enjoyable activities. For someone who has had a stroke or has physical difficulties, treatment will also include rehabilitation. The drugs that are routinely prescribed for Alzheimer’s disease do not have benefits for vascular dementia, and are not recommended for it. These drugs may, however, be prescribed to treat mixed dementia (Alzheimer’s disease and vascular dementia). If someone is depressed or anxious, talking therapies (such as cognitive behavioural therapy) or drug treatments may also be tried. Counselling may also help the person adjust to the diagnosis

Learn about the recommended dose for different types of prescribed drugs, what form they are dispensed in and also what to do if a dose is missed.

Taking drugs as prescribed

he person should take the drugs as prescribed and the doctor should try to ensure this is done. The person may benefit from using a pill box with different compartments for each day of the week, containing the prescribed dose. The pharmacist may be able to supply drugs pre-packed in this way.

Missing a dose of drugs

Doses vary. Usually a person with Alzheimer’s disease will start on a low dose, which will be increased later to make the treatment more effective. Some people may not be able to take the highest dose because of side effects. The doctor will prescribe the best dose for each individual.

How much is a normal dose?

If the person misses a dose of any of these drugs, they should take it as soon as they remember, as long as it is on the same day. If it is the next day, the person should not take two tablets, but should simply continue with their normal dose.

Donepezil

• Donepezil is available in 5mg or 10mg tablets. It is taken once a day, usually at bedtime.
• Treatment is started at 5mg a day and then increased to 10mg a day after one month, if necessary.
• The maximum licensed total daily dose is 10mg.

Rivastigmine

• Rivastigmine comes in capsules or a solution to drink. It is taken twice a day, with morning and evening meals.
• People start with 3mg a day in two divided doses, which will usually increase (at intervals of at least two weeks) to between 6mg and 12mg a day.
• The maximum licensed total daily dose for oral rivastigmine is 12mg.

Rivastigmine patches are also available. These deliver daily doses of 4.6mg, 9.5mg or 13mg, with fewer side effects than the capsules. Patches are suited to people who struggle with taking medication by mouth; they are popular with carers. Only one patch should be applied at any one time and it should be put on different parts of the skin each time, to avoid the person getting a rash.

Galantamine

• The recommended starting dose for galantamine is 8mg each day for four weeks. It is then increased to 16mg a day for another four weeks, then kept at a dose of between 16 and 24mg daily.
• Galantamine is made in a variety of forms including a 4mg/ml (twice-daily) oral solution, and tablets of 8mg and 12mg.
• Slow-release (XL) capsules are available in doses of 8mg, 16mg and 24mg. These are popular because they only need to be taken once a day.
  The maximum licensed total daily dose for galantamine is 24mg.

Memantine

• Memantine comes in two forms: as 10mg and 20mg tablets, and as 10mg oral drops.
• The 10mg tablets can be broken in half (into 5mg doses) and taken with or without food.
• The recommended starting dose is 5mg a day, increasing every week by 5mg, up to 20mg a day after four weeks.
• The maximum licensed total daily dose for memantine is 20mg.
• According to NICE guidelines (2011),  it states the specialist should seek the views of the carer on the condition of the person with dementia, before treatment and during follow-up appointments. They should also seek the views of the person with dementia.

We suggest some helpful questions that you may wish to ask your doctor, plus we provide insight in to process of stopping medication.

Questions to ask the doctor when starting the drugs

It is important that someone who has been prescribed drugs understands what it does and how to take it. It may be helpful for the person with dementia or their carer to write down the following questions, and any answers the doctor provides.

• Why have I been prescribed this drug specifically?
• What are the potential benefits of taking this drug?
• How long will it be before I see a result?
• If I get side effects, should I stop taking the drug immediately?
• What will happen if I stop taking the drug suddenly?
• Can I drink alcohol while taking the drug?
• How might this drug affect other medical conditions?
• What changes in health should I report immediately?
• How often will I need to visit the clinic or surgery?
• If this drug doesn’t suit me, can I try another drug?

Stopping treatment

Medication should be reviewed regularly, and continued for as long as the benefits outweigh any side effects.

Making the decision to stop medication

If the person with Alzheimer’s decides to stop taking a drug, they should speak to the doctor first if possible, or as soon as they can after stopping treatment.
Treatment may also be stopped by agreement with the doctor if the person becomes unable to take the medicines in the prescribed way, even with support.

Stopping and restarting

If someone stops taking their prescribed drug, their condition may get worse more quickly. If someone has stopped and thinks they should restart their medication, it is important that they contact their doctor as soon as possible.

Cholinesterase inhibitors

For someone who is taking a cholinesterase inhibitor, a decision will need to be made when their Alzheimer’s disease becomes severe. There is now good evidence that cholinesterase inhibitors continue to bring benefits even when someone’s Alzheimer’s is severe. Many doctors therefore continue to prescribe a cholinesterase inhibitor for severe Alzheimer’s until the above criteria for stopping treatment are met, if ever.

The issue of whether to add memantine to the cholinesterase inhibitor for someone with severe Alzheimer’s disease (known as combination treatment) is less clear cut. The two drugs work in different ways and there is research evidence that, for someone who is already on donepezil, adding memantine might bring additional benefit. However, NICE guidance (2011) does not recommend combination treatment.

Learn about guidance provided by The National Institute for Health and Care Excellence regarding access to available drugs for Alzheimer’s disease, published in 2011. The National Institute for Health and Care Excellence (NICE) provide national evidence-based guidance and advice for health, public health and social care practitioners. In 2011, NICE issued revised guidance on Alzheimer’s disease drugs. It recommended that people with Alzheimer’s disease (or mixed dementia in which Alzheimer’s is the main cause) should have increased access to the available drugs.

Who should drugs be prescribed to?

The current NICE guidance on drug treatments for Alzheimer’s disease recommends that people in the mild-to-moderate stages of the disease should be given treatment. Types of drugs include donepezil, galantamine or rivastigmine, and it should include individuals with both Alzheimer’s disease and learning disabilities. It further recommends that memantine should be prescribed as part of NHS care for people with severe Alzheimer’s disease, or for those with moderate disease who cannot take the cholinesterase inhibitor drugs.

Measuring the severity of dementia

NICE also says that, when considering drug treatment, how severe someone’s dementia has become should not be measured by scores on mental ability tests alone, but by a broader view of the person’s condition. An example of such a test includes the Mini Mental State Examination(MMSE). This is to avoid an arbitrary decision to stop drug treatment, such as when the person’s MMSE score has crossed a threshold from moderate to severe or because they have gone into a care home.

Drugs for dementia with Lewy bodies, or Parkinson’s disease dementia

NICE guidelines allow people with dementia with Lewy bodies or Parkinson’s disease dementia to be offered a cholinesterase inhibitor if their non-cognitive symptoms, such as  hallucinations or agitation, are causing distress or leading to challenging behaviour. The consultant will decide whether these treatments are appropriate for a particular individual.

Drugs for Alzheimer’s disease

In relation to the Alzheimer’s disease drugs, NICE makes the following recommendations:

• Treatment is started by a doctor who specialises in the care of people with dementia.
• People who are started on one of the drugs are checked regularly, usually by a specialist team unless shared care arrangements with primary care are in place.
• The check-up includes an assessment of the person’s mental abilities, behaviour and ability to cope with daily life.
• The views of the carer on the person’s condition are discussed at the start of drug treatment and at check-ups.
  Treatment is continued as long as it is judged to be having a worthwhile effect.
• Where a cholinesterase inhibitor is given, the least expensive of the three drugs (currently donepezil) is prescribed first. However, if donepezil is not suitable for the person, another cholinesterase inhibitor could be chosen.