Donepezil, rivastigmine and galantamine

Donepezil, rivastigmine and galantamine are the most common memory medicines for dementia. Together they are called cholinesterase inhibitors. Doctors have prescribed them for many years.

These medicines do not cure dementia or stop it from getting worse. For some people, they ease symptoms or hold them steady for a while.¹ This page explains what to expect, which side effects to watch for, and how families and doctors decide when to stop.

How these medicines work

The brain uses chemical messengers to pass signals between nerve cells. One of them, acetylcholine, is important for memory and learning. In Alzheimer's disease, the brain makes less of it as cells are damaged.¹

The body has an enzyme (a natural chemical that breaks things down) called cholinesterase. It clears acetylcholine away after each signal. Cholinesterase inhibitors slow that enzyme. This leaves more acetylcholine available, so the remaining nerve cells can signal a bit better.¹

They do not stop the damage to brain cells, so the disease keeps moving forward underneath.¹

The three medicines (and a newer form)

There is also a combination pill, Namzaric, that joins donepezil with memantine. It is approved for moderate to severe Alzheimer's disease.¹

Other types of dementia. In the U.S., rivastigmine is the only one of these approved for Parkinson's disease dementia.³ A national guideline from the United Kingdom recommends donepezil or rivastigmine for Lewy body dementia.⁹ The same guideline says these medicines should not be used for frontotemporal dementia. For vascular dementia, it suggests them only when Alzheimer's or Lewy body disease is likely also present.⁹

None of these medicines is approved for mild cognitive impairment. In two long studies of galantamine in people with MCI, more people died in the galantamine group than in the placebo group. The FDA label notes this result did not match other galantamine studies.⁴

How much do they help?

The best summary of the research comes from a 2018 Cochrane review of donepezil. It pooled 30 studies with more than 8,000 people with Alzheimer's disease.⁵ After about six months, people on donepezil did slightly better than people on a placebo (a look-alike pill with no medicine):⁵

• Memory and thinking: about 1 point better on a 30-point memory test (the MMSE), and about 2.7 points better on a 70-point test (the ADAS-Cog).
• Daily life and overall picture: small gains in doctors' overall ratings, and in daily skills for people with severe dementia.
• Behavior and quality of life: no clear difference.

The reviewers rated this evidence as moderate quality and called the benefits small.⁵ Higher doses did not help much more than lower ones but caused more side effects.⁵ A UK guideline treats all three as options for mild to moderate Alzheimer's. It suggests choosing based on cost, side effects, other health problems and other medicines.⁹

What this means in daily life. A 1-point change on a 30-point test is hard to notice at home. Some families see a person become a little more alert, engaged or able to follow a conversation. Others see no change. Even with the medicine, the disease keeps progressing.^1,8 A "steady for now" result can still be a success, because the usual course is slow decline.

Ask the doctor how long to wait before judging whether the medicine is helping. Keep simple notes on mood, memory, sleep and daily tasks. A memory notebook can help you bring examples to the doctor.

Side effects

Most side effects come from the same extra acetylcholine that helps memory. It also acts on the stomach, gut, heart and muscles. Many side effects are more common at higher doses or when the dose is raised quickly.^2,3 Your doctor starts low and goes slow to help the body adjust.

How often. In donepezil studies, about 11 in 100 people had nausea, compared with 6 in 100 on placebo. About 3 in 100 had abnormal dreams, compared with none on placebo.² Galantamine caused nausea in about 1 in 5 people.⁴ In the Cochrane review, about 1 in 4 people on donepezil dropped out early, compared with about 1 in 5 on placebo.⁵

Vivid dreams and sleep. Bad dreams or restless nights can upset both the person and the caregiver. If this happens, ask the doctor or pharmacist whether taking the medicine at a different time of day might help. Do not change the timing on your own.

Slow heartbeat, fainting and falls

These medicines can slow the heartbeat and the signals that control heart rhythm. This can cause dizziness or fainting.^2,3 The risk is higher in people who already have a slow pulse or a heart rhythm problem. It is also higher when combined with heart medicines that slow the pulse, such as beta-blockers.³

A large study in Ontario, Canada, followed about 20,000 older adults with dementia who took these medicines. Compared with similar people not taking them, they had:⁶

• About 1.8 times as many hospital visits for fainting (about 3 in 100 people a year, compared with about 2 in 100)
• More hospital visits for a slow heartbeat
• More pacemakers put in
• Slightly more hip fractures

Before starting, the doctor may check the pulse and may order an ECG (a simple heart rhythm test). Tell the doctor about any fainting, falls or heart problems. See our page on preventing falls.

The rivastigmine patch

Rivastigmine is the only one of these medicines that comes as a patch worn on the skin. The medicine passes slowly through the skin over a full day. This gives steadier levels in the blood.³

In the main study, the patch caused far less stomach upset than rivastigmine capsules. About 7 in 100 people on the patch had nausea, compared with 23 in 100 on capsules. About 6 in 100 vomited, compared with 17 in 100.³

The patch can also help when a person has trouble swallowing pills, or refuses them. A caregiver can see whether it is on. Some practical points from the FDA label:³

• A new patch goes on once a day, at about the same time. Always take off the old patch first. Wearing more than one patch at a time has led to hospital stays and rare deaths.
• The upper or lower back is the preferred spot. The upper arm or chest can also be used.
• Put it on clean, dry, hairless skin with no lotion or powder. Use a new spot each day, and wait at least 14 days before reusing the same spot.
• If a patch falls off or is missed, follow the pharmacist's directions. Never put on two patches to make up for one.
• Avoid long exposure to heat, such as saunas, tanning beds or strong sun, while wearing it.

If treatment stops for more than a few days, call the doctor before restarting. Starting again at the old dose can cause severe vomiting. The doctor may need to restart at a low dose.³

When to stop

There is no set end date for these medicines. Many people take them for years. But as dementia advances, the balance of benefit and burden can change. Two expert groups look at this a bit differently:

• A UK national guideline says doctors should not stop these medicines just because the dementia has become severe.⁹
• A deprescribing guideline from Australia and Canada says that after a year of treatment, it is reasonable to try stopping in some situations.^7,8 Examples include when thinking or daily skills have dropped a lot in the past six months, when the medicine never seemed to help, or when dementia is severe or end-stage.⁸

Other reasons to talk about stopping include side effects, trouble swallowing pills, a new serious illness, or simply the person's or family's wishes.⁸

How stopping works. The doctor usually lowers the dose in steps, about every four weeks, then stops. If side effects are the reason, stopping right away may be fine.⁸ The doctor then checks in, often about four weeks later. If the person clearly gets worse, the doctor first looks for other causes, such as an infection or dehydration. Then the medicine may be restarted.⁸

Families should know the person will keep declining after stopping, because the disease continues either way.⁷ A trial off the medicine is not giving up. It is a way to find out whether the medicine is still doing anything.

1. Write down what you have noticed since the medicine started: memory, mood, sleep, appetite, falls and daily tasks.
2. Bring a full list of all medicines, including over-the-counter ones and supplements. Some common drugs can make memory worse. See medicines that can worsen memory.
3. Ask the doctor what a good result would look like, and how you will both judge it.
4. If you decide to stop, agree on a plan, a check-in date and the signs that mean you should call.

For people near the end of life, review all medicines with the hospice or palliative care team.

Questions to ask the doctor

Is this medicine right for us?

• Which type of dementia is this, and does the medicine fit it?
• Would the patch be a better choice than pills?
• Should we add memantine now or later?
• Could this be combined with newer treatments like lecanemab?

What about safety?

• Do any of my heart conditions, heart medicines or stomach problems raise the risk?
• Should we check my pulse or get an ECG before starting?
• What side effects should make us call you right away?

How will we know if it is working?

• How long should we wait before judging?
• What changes should we track at home?
• When should we review whether to keep going or stop?

For help finding care and answers about treatment, the Alzheimer's Association 24/7 Helpline is 800-272-3900. For a mental health crisis, call or text 988. Learn more about other options on our dementia medicines page.

Education only. This page is general information written from the sources listed. It is not medical, legal or financial advice and does not replace a doctor, therapist or lawyer who knows your situation. How we write and check pages.