Memantine

Memantine (brand name Namenda) is a medicine for the symptoms of Alzheimer's disease in its moderate and severe stages. It can help with thinking, daily tasks and mood for a while. It does not cure Alzheimer's or stop it from getting worse.^1,8

Many families first hear about memantine when a loved one moves into the middle stage of dementia. It is often added to donepezil, an older memory medicine. This page explains what memantine can and cannot do, how it is combined with donepezil, and which side effects to watch for.

What memantine does

Memantine works on glutamate. Glutamate is a chemical messenger that brain cells use to pass along signals for learning and memory.⁷ Memantine partly blocks one type of glutamate receptor, called the NMDA receptor (a docking spot on nerve cells). Doctors call it an NMDA receptor antagonist.^1,8

This is a different action from the cholinesterase inhibitors, such as donepezil, rivastigmine and galantamine. Those medicines boost a different brain messenger, acetylcholine. Because the two kinds work in different ways, doctors sometimes use them together.⁷

The FDA label states that there is no proof memantine slows or prevents the loss of brain cells.¹ It eases symptoms for a time. The disease itself keeps moving forward. Memantine is also very different from newer drugs like lecanemab, which remove amyloid and are only for early-stage disease.

Who is it for?

Memantine is approved for people with moderate to severe dementia due to Alzheimer's disease.¹ In these stages, a person usually needs help with daily tasks such as dressing, bathing or managing money. See middle-stage dementia and late-stage dementia.

It is not approved for mild Alzheimer's or for mild cognitive impairment. A large Cochrane review (a careful summary of all the good studies) found no meaningful benefit in mild Alzheimer's. People with mild disease were also about twice as likely to stop the drug because of side effects.⁴

Other types of dementia

Doctors sometimes use memantine for other dementias. The evidence is weaker:

• Vascular dementia: The Cochrane review found a probable small benefit for thinking, but no clear change in daily function.⁴ The UK's national guideline (NICE) advises using it only if Alzheimer's, Lewy body dementia or Parkinson's disease dementia may also be present.⁶ See vascular dementia.
• Lewy body dementia and Parkinson's disease dementia: There may be a small benefit, but the studies are few and small.⁴ NICE says doctors can consider memantine when cholinesterase inhibitors are not tolerated.⁶ See Lewy body dementia.
• Frontotemporal dementia: There is too little evidence that it helps. NICE advises against using it for this type.^4,6 See frontotemporal dementia.

How much does it help?

The short answer is: a little, for a while. The table below sums up the main research. Strong evidence

What this means in daily life. In these studies, people on memantine still got worse over time. They tended to decline a bit more slowly on thinking and daily-task tests than people on placebo.^1,4 On a 54-point daily-living scale, the difference in the first FDA study was about 3 points.¹ Some families notice that a loved one is a little more alert or a little easier to help. Others notice no change.

Most studies lasted about six months. The Cochrane authors said longer studies are needed to know how much benefit lasts beyond that.⁴

Does it help with agitation?

People taking memantine reported agitation as a side effect a little less often than people on placebo. But in studies that measured agitation directly, memantine did not clearly calm it.⁴ For agitation, the first steps are finding causes like pain, infection or noise. See agitation and aggression and medicines for agitation.

Memantine together with donepezil

Many people in the moderate stage already take donepezil. Doctors often add memantine on top. This is called combination therapy.

What the research shows

• In the FDA study of 404 people already on donepezil, adding memantine led to better thinking and daily-living scores over 24 weeks than adding a placebo.¹ Moderate evidence
• A later British study called DOMINO followed 295 people with moderate to severe Alzheimer's for a year. Memantine helped thinking and daily function compared with placebo. But adding memantine to donepezil did not give a clear extra benefit over donepezil alone.⁵
• The Cochrane review found that taking a cholinesterase inhibitor did not change memantine's overall benefit.⁴

So the results are mixed. The combination is widely used and generally well tolerated. The extra benefit, if any, is modest.

Keep taking donepezil?

The DOMINO study also found something important for families. People who kept taking donepezil did better on thinking and daily function over the year than people who stopped it.⁵ NICE advises that a cholinesterase inhibitor should not be stopped just because the disease has become more severe.⁶ It also advises doctors to consider adding memantine in moderate Alzheimer's and to offer it in severe Alzheimer's.⁶

The combination capsule (Namzaric)

In 2014, the FDA approved Namzaric. It is one capsule that holds long-acting memantine and donepezil.² It is meant for people already settled on both medicines. It means one less pill to swallow. The capsule can be swallowed whole or opened and sprinkled on applesauce. It should not be chewed, crushed or divided.² Ask your pharmacist whether this works for your loved one.

Forms of memantine

Memantine comes in several forms:^1,8

• Regular tablets
• Long-acting (extended-release) capsules, sold as Namenda XR
• A liquid (oral solution), which may help a person who has trouble swallowing pills
• The combination capsule with donepezil (Namzaric)²

Your doctor starts low and goes up slowly over several weeks. This gives the body time to adjust and lowers the chance of side effects. Always follow the plan from the doctor and pharmacist. For tips on pill boxes, reminders and refusals, see managing medicines at home.

Side effects

Most people tolerate memantine well. In FDA studies, people on memantine stopped the drug because of side effects about as often as people on placebo (about 1 in 10 in both groups).¹

The most common side effects in the FDA tablet studies were:¹

With the long-acting capsule, the most common side effects were headache, diarrhea and dizziness.² The Cochrane review found no difference in falls between memantine and placebo.⁴

Other possible side effects include sleepiness, nausea, vomiting, back pain, cough and changes in mood.⁸

Side effects of the combination

When memantine is taken with donepezil, donepezil's own side effects also apply. These include nausea, vomiting, diarrhea, loss of appetite and bruising.² Donepezil can also slow the heart rate, which can cause fainting.² Read more on the cholinesterase inhibitors page.

Safety tips and things to tell the doctor

Before starting memantine, tell the doctor and pharmacist about:^1,8

• Kidney disease. Memantine leaves the body through the kidneys. People with severe kidney problems may need a lower amount.
• Seizures in the past.
• Bladder or urine problems, including trouble passing urine.
• Liver disease.
• Every other medicine and supplement, including over-the-counter products.

Medicines and products to watch

• Cough medicines with dextromethorphan (often marked "DM"). Dextromethorphan acts on the same brain receptor, so combining them calls for caution.^1,8
• Amantadine and ketamine also act on this receptor. They have not been well studied with memantine.¹
• Baking soda (sodium bicarbonate) and some other drugs can make urine less acidic. This can slow how fast memantine leaves the body and raise side effects.^1,8
• Alcohol can make side effects worse.⁸
• Surgery, including dental surgery: tell the surgeon or dentist about memantine, and about donepezil if it is part of the plan.^2,8

Some other common medicines can make memory and thinking worse. See medicines that can worsen memory. A yearly "brown bag" review, where you bring every pill bottle to the doctor or pharmacist, is a good habit.

Later-life points to keep in mind

Many people who take memantine are older adults. A few things matter more in later life:

• Kidneys slow down with age. The doctor may check kidney function with a blood test.¹
• Dizziness can raise fall risk. Watch closely during the first weeks and after any change.
• Many pills. Older adults often take many medicines. Ask whether every one is still needed.
• Swallowing. If pills become hard to swallow, ask about the liquid or the sprinkle capsule. Do not crush long-acting capsules.²

When to stop or reconsider

There is no set time to stop memantine. Families and doctors usually revisit the choice when:

• Side effects are bothering the person more than the medicine seems to help.
• Swallowing becomes very hard.
• The person moves toward late-stage care or hospice, and the focus shifts fully to comfort.

The research on how long the benefit lasts is limited.⁴ In the DOMINO study, people who stopped donepezil did worse than those who kept taking it.⁵ That is why any change should be planned with the doctor, not done on your own.

Is memantine a cure?

No. It eases symptoms for a time in moderate to severe Alzheimer's. The disease keeps getting worse, but perhaps a little more slowly.^1,4

Can someone with mild Alzheimer's take it?

It is not approved for mild Alzheimer's. Studies in mild disease found no clear benefit and more side effects.⁴ If a doctor suggests it for mild disease, ask what benefit they expect.

Is it safe to take with donepezil?

Yes, the two are often taken together. Donepezil does not change how the body handles memantine, and memantine does not change donepezil.¹ A combination capsule (Namzaric) is available.²

Will memantine help with behavior problems?

It may help mood and behavior a little in moderate to severe Alzheimer's. It has not been shown to calm agitation that is already happening.⁴ Non-drug approaches come first.

Questions to ask the doctor

• What stage is my loved one in? Is memantine a good fit now?
• What changes should we watch for, and how soon?
• Should it be added to donepezil, or used instead?
• Would the liquid, the long-acting capsule or the combination capsule be easier?
• Are any of their other medicines a problem with memantine?
• How will we decide if it is working, or when to stop?

For an overview of all dementia medicines, see dementia medicines. Learn how the strength of evidence is rated on our evidence 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.