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Memantine
Memantine: A Different Mechanism in Moderate to Severe Dementia
Memantine is an NMDA receptor antagonist used in moderate to severe Alzheimer’s dementia. It dampens abnormal constant overstimulation by the messenger substance glutamate without blocking normal signal transmission. It is usually better tolerated than the cholinesterase inhibitors, but it does not halt the disease either — its benefit lies in stabilising everyday abilities and behaviour for a time.
Film-coated tablets, orodispersible tablets and oral drops, usually 10 mg and 20 mg
Half-life
Around 60 to 100 hours — very long; one dose a day is enough, and the level builds up over several days
Maximum daily dose
20 mg according to the SmPC; considerably less with impaired kidney function — the dose is set by the treating practice
Onset of effect
Can be judged after several weeks at the earliest; assessment usually after about three months
Indication
Moderate to severe Alzheimer’s dementia
Elimination
Mainly unchanged via the kidneys — the key point for dose and safety
Prescription status
Prescription-only medicine
Notable feature
A different mechanism from the cholinesterase inhibitors: hardly any digestive complaints, no slowing of the heartbeat
Table scrolls to the right
2. How it works: damping down the glutamate flood
Glutamate is the most important excitatory messenger substance in the brain. Without it there would be no learning and no memory. Among other places, it acts at what is known as the NMDA receptor, which you can picture as a channel in the cell wall: when a short, strong signal arrives, it opens, calcium flows in and the nerve cell stores something. Then it closes again.
In Alzheimer’s dementia this system gets out of step. Glutamate stays permanently raised, the channel is constantly open a crack, and calcium trickles into the cell without let-up. First, nerve cells die from this constant strain. Second — and this is the crucial point in everyday life — the actual signal gets lost in the background noise: a transmitter that is sending quietly without a break no longer gets a clear message across.¹,²
This is exactly where memantine comes in. It does not block the NMDA receptor permanently or completely, but binds only loosely and can be pushed out again by a strong signal. In technical terms: an uncompetitive antagonist with low affinity and fast receptor kinetics. In practice, that means:
The constant noise is damped, because weak, persistent glutamate signals no longer hold the channel open.
Normal signal transmission remains possible, because a strong burst of glutamate pushes memantine out of the channel. That is why memantine does not make people dull or dazed, as a complete blockade would.
The signal-to-noise ratio improves — this is how it is explained that attention and everyday functioning can stay more stable for a time.
The difference in one sentence.Donepezil and the other cholinesterase inhibitors boost a signal that is too weak (acetylcholine). Memantine damps down one that is too loud (glutamate). Two different problem areas of the same disease — which explains both the different stages at which they are used and their completely different side effect profiles.
3. When memantine is used — the stage decides
This is the key difference from the cholinesterase inhibitors and the most common reason for questions: memantine is licensed for moderate to severe Alzheimer’s dementia, the cholinesterase inhibitors for mild to moderate. So there is an area of overlap — and below and above it, a clear allocation in each case.²
Stage
What is typically in the foreground
Usual approach with medicines
Mild
Forgetfulness, finding words, finding your way in unfamiliar surroundings; everyday life largely independent
Cholinesterase inhibitors; memantine is not licensed here and has no proven benefit
Moderate
Help needed with dressing, personal care and housework; behavioural problems increase
Cholinesterase inhibitors or memantine; in certain situations both
Severe
Extensive need for care, speech severely limited
Memantine; cholinesterase inhibitors are not licensed here
Table scrolls to the right
This matters for families, because a change of medicine is often experienced as a step backwards: “Now she’s getting the other medicine.” But it is not a sign of failure — it is an adjustment to a changed stage. The reverse also applies: anyone with mild dementia, or just forgetfulness without a confirmed diagnosis, does not benefit from memantine according to current knowledge. How dementia is classified and what the individual stages mean is explained in the article on the condition.
4. What memantine can do — and what it can’t
Like all anti-dementia medicines available today, memantine works on the symptoms. It does not remove protein deposits, does not repair nerve cells that have died and does not halt the course of the disease. If you expect an improvement, you will be disappointed; if you accept a slower decline as the goal, you can judge the benefit fairly.
A realistic goal: stabilising everyday abilities and cognitive performance over a limited period. In studies, treated groups show better scores on average than untreated groups on scales of everyday functioning and cognition.³
A second target: behavioural symptoms such as restlessness or aggression can be favourably influenced — more on this in section 10.
Size of the effect: moderate on average and not noticeable in everyone. Some families report calmer evenings and better responsiveness; others notice no difference for months. Both are consistent with the evidence.
What memantine is not: a tranquilliser or sleeping pill. Care, a daily structure and activities remain the foundation of all dementia treatment.⁴
Set two or three everyday markers before starting. Not “is he any better?” but: does she eat without being prompted? Does he recognise the grandchildren? How many restless evenings were there this week? Concrete points like these, noted down before treatment starts, are the only reliable yardstick. Without them, after three months you will be guessing rather than assessing.
5. Dosing: why the dose is increased in small steps
The information below describes the usual approach set out in the SmPC. It is not a dosing instruction — the dose and how quickly it is increased are set by the treating practice.
Start low: treatment begins with a small daily dose that is increased in weekly steps. There are starter packs with different strengths for this phase.
Increase over several weeks: the maintenance dose is usually only reached after about four weeks. This reduces dizziness and confusion at the start.
Maintenance dose: usually 20 mg daily according to the SmPC.¹
With impaired kidney function: the dose is reduced depending on the measured kidney function — see section 8 for details.
Worth knowing: unlike with the cholinesterase inhibitors, the gradual increase here is not mainly about nausea but about effects on the brain — dizziness, drowsiness and a temporary increase in confusion typically occur in the first few weeks and often ease afterwards.
6. Taking it: drops, tablets, missed doses
Memantine is taken once a day, regardless of meals. Unlike donepezil, there is no compelling reason to take it in the evening — what matters is a fixed time that is always the same.
Link the fixed time to a routine. In dementia it is the routine that carries things, not memory. The tablet belongs at an immovable point in the day — with breakfast, with the evening meal.
Match the dosage form to the situation. If tablets are hard to swallow, orodispersible tablets or drops are an alternative. Drops also allow fine intermediate steps while the dose is being increased. Which form suits is decided by the practice together with the pharmacy; whether a particular tablet may be split is covered in the guide Splitting tablets.
Missed dose: it is usually not made up; instead, carry on as normal the next day — a double amount is not the answer. General rules are in the guide Missed a medication.
Keep an eye on fluid intake. With memantine, drinking enough is not just generally sensible — it is directly linked to elimination via the kidneys, see section 8.
Who gave the tablet today?
A shared dose history prevents double doses and gaps within the family.
7. Side effects: what you notice and what stays away
Memantine is regarded as comparatively well tolerated — and in everyday life that is a real argument in its favour, especially for people who already eat little and take many other medicines.
What typically occurs
Dizziness and drowsiness — above all while the dose is being increased. This matters because dizziness raises the risk of falls in older people.
Headache — common at the start, usually temporary.
Increased confusion — only uncommon according to the SmPC, but known: in the first few weeks disorientation can temporarily increase before it settles again. If it increases markedly or persists, it needs a medical assessment — there may be a quite different cause behind it, such as a urinary tract infection or a lack of fluid.
A rise in blood pressure — this has been described and is a reason to check blood pressure occasionally while taking memantine, especially if high blood pressure is already present.
Rarely: seizures, hallucinations, psychotic reactions — with known epilepsy or a history of seizures, memantine is used with particular caution.
What — unlike with cholinesterase inhibitors — usually does not happen
Marked digestive complaints. Nausea, diarrhoea and loss of appetite are much less common on memantine. For people with dementia who are already losing weight, that is a weighty argument.
A slowed heartbeat. Memantine does not interfere with the cholinergic control of the heart. Bradycardia and the fainting it can cause are not a typical issue — unlike with the cholinesterase inhibitors, where the combination with beta blockers needs particular attention.
What should be reported, and how, is explained in the guide Medication side effects. In dementia there is one particular point: the people affected often can no longer put their complaints into words. Family members and carers are the real observers — changes in walking, eating or mood count as much here as a reported symptom.
8. Focus on kidney function: the most important safety point
Most medicines are broken down in the liver before they leave the body. Not memantine: it is mainly excreted unchanged via the kidneys. So the drug level in the blood depends almost directly on how well the kidneys are working. If kidney function declines, more memantine stays in the body — and a usual dose becomes too high.¹
This is not a theoretical problem: kidney function declines with age anyway, and the people who take this medicine are old. In dementia, too, people often drink too little — a feverish infection or a hot summer’s day can be enough to worsen kidney function noticeably.
Before treatment starts: kidney function is measured — usually via creatinine and the eGFR or creatinine clearance calculated from it.
Dose adjustment: with moderately impaired kidney function the maintenance dose is reduced, and with severe impairment it is kept at the reduced level. The exact thresholds are in the SmPC and are applied individually.
Over time: regular checks, because kidney function changes over the years. How to make sense of such results is explained in the guide Understanding blood values.
When something happens: with fever, diarrhoea, vomiting, a heatwave or new water tablets. These are exactly the situations in which kidney function tips over fastest.
The second, often overlooked point: the pH of the urine. Memantine is excreted via the kidneys, and this excretion falls markedly when the urine becomes more alkaline — the drug level then rises. Triggers can include a drastic switch to a purely plant-based diet, certain medicines that make the urine alkaline, sodium bicarbonate (baking soda) as a home remedy for heartburn, or a urinary tract infection with certain bacteria. Changes like these should be discussed with a doctor — especially if new confusion or dizziness appears at the same time. The basics are covered in the guide Medications in kidney and liver disease.
If chronic kidney disease is already present, memantine is not forbidden — it is simply given at a lower dose and monitored more closely. With very severe kidney failure, its use is usually not recommended. This weighing-up is done by the treating practice, and it is a good opportunity to go through the entire medication list for substances that put a strain on the kidneys.
Memantine has fewer interactions than the cholinesterase inhibitors, and different ones. Two patterns explain almost all of them: substances that act on the same receptor system, and substances that share the same transport route through the kidneys.
Combination
Consequence
What to do
Other NMDA antagonists (amantadine, ketamine, dextromethorphan in cough medicines)
Increased effects on the brain, risk of psychosis and confusion
Avoid the combination if possible; have over-the-counter cough medicines checked before buying
Levodopa and other Parkinson’s medicines
Their effect can be increased
If Parkinson’s is being treated at the same time, coordinate with the doctor
People with dementia rarely take just one medicine. A complete, up-to-date list that includes over-the-counter products is the basis of every review — background in the guide Drug interactions and under Polypharmacy. How to build such a list in a structured way is shown in Creating a medication plan. On alcohol, it is worth looking at Medications and alcohol. Memantine also belongs on the list before any operation — what needs to be clarified is set out in the guide Medications before surgery.
10. Restlessness and aggression: what memantine can do here
For families, it is rarely the memory gaps that make everyday life impossible. It is the behavioural symptoms: inner restlessness, wandering, resisting care, mistrust, irritable or aggressive reactions, getting up at night. This is where the call for a tablet is loudest — and exactly where particular care is needed.
To put this in context, in this order:
First look for treatable triggers. Pain, a urinary tract infection, constipation, thirst, feeling overwhelmed, too much noise, too full a day, new surroundings. A large proportion of sudden restlessness has a physical or situational cause — and that does not go away with a psychiatric drug.
Non-drug approaches come first. Daily structure, exercise, familiar routines, calm conversation, activities. This is harder work than a tablet, yet the guideline still makes it the first choice.²
Memantine can make a contribution. There is evidence that memantine has a favourable effect on behavioural symptoms such as restlessness and aggression. The effect is moderate, does not appear immediately and does not replace points 1 and 2 — but it is an argument when a decision about an anti-dementia medicine is being made anyway.
Antipsychotics only with restraint. Medicines such as quetiapine or risperidone are used in dementia only when the burden is considerable, at the lowest possible dose and for a limited time. The reason is serious: in older people with dementia, antipsychotics have been associated with an increased risk of stroke and increased mortality.⁵ Their use should be reviewed regularly and ended as soon as possible.
Sedating someone is not a treatment goal. If a medicine is given mainly so that someone “finally settles down”, that is a warning sign — both for the strain on the carers and for the safety of the person affected. Long-term sedation increases the risk of falls, pneumonia and death. The right way forward is not more medicine but more support: care counselling, day care, respite services. Talk openly about feeling overwhelmed at the practice — it is a medically relevant finding, not a failure. More on risks in older age in the guide Medications in old age.
11. Combining it with a cholinesterase inhibitor
Because the two groups of drugs act at completely different points, it is tempting to combine them. In more advanced stages this is a possible option, and pharmacologically there is nothing against it: they do not cancel each other out, and their side effect profiles hardly overlap.
The evidence on additional benefit is, however, mixed — the effects of a combination compared with a single medicine are small, if present at all. That is why it is not used routinely but considered case by case: for instance, when the moderate stage is reached while on a cholinesterase inhibitor and it is well tolerated. The decision is a medical one, made after weighing up the stage, other conditions, kidney function and the number of tablets already being taken.
12. Families, adherence and when to stop
In dementia, taking medicines reliably is not a question of discipline but of organisation — and usually organisation by someone else. Someone who cannot remember whether the tablet has already been taken takes it either twice or not at all. That is the disease, not a lack of goodwill.
A weekly pill organiser or blister packing — one glance is enough to see whether the dose is still in its compartment.
One fixed person responsible per time slot — double doses almost always happen at hand-over points between people, especially at weekends.
A digital reminder with confirmation — not intended for the person with dementia, but for the carers: the history shows whether the dose was actually given.
And when is it stopped? Anti-dementia medicines are sometimes continued for years without anyone asking whether they still help. Reasons for a joint review are: no recognisable benefit measured against the everyday markers agreed in advance, troublesome side effects, very advanced disease or persistent swallowing problems. It is usually not stopped abruptly, and the period afterwards is observed. How an orderly attempt to stop works is explained in the guide Stopping medications.
Never stop on your own. Neither out of disappointment that it isn’t working nor because “it’s not doing anything any more anyway”. If it is restarted, the dose has to be built up gradually again, and the time in between may cost stability. Instead, ask for a review appointment — that is a legitimate reason and one that is expressly provided for, especially in advanced stages and in the last phase of life.
13. Memantine experiences: what patients and families really ask
“Why is my mother getting a different medicine now?”
Switching from a cholinesterase inhibitor to memantine is as a rule not a reaction to the previous treatment failing, but an adjustment to the stage: memantine is licensed from moderate dementia onwards, the cholinesterase inhibitors only up to that point. For many families this switch is emotionally hard, because it makes the progression of the disease visible. It helps to see it for what it is medically — a continuation of treatment by other means, not its end.
“He has been even more confused since starting it”
A temporary increase in confusion and dizziness in the first few weeks is known and one of the reasons for increasing the dose slowly. It should settle. If it persists or increases markedly, it needs a medical assessment — there is then often a quite different cause behind it: a urinary tract infection, drinking too little, pain, a new medicine, or worsened kidney function that has made the memantine level rise. Note down when the change began and take this record with you to the practice.
“Do regular blood tests need to be done?”
Memantine does not need drug level monitoring as lithium does, for example. The kidney values are important, though, because they decide the right dose — and they change with age, with infections and with water tablets. At the next appointment, ask specifically when kidney function was last measured.
Kidney values, dose and doses taken — all in view together
So that at the next appointment it is clear what was given and what has changed.
Memantine blocks the NMDA receptor, where the messenger substance glutamate acts. In Alzheimer’s this system is permanently overstimulated, so real signals get lost in the background noise. Memantine binds only loosely and can be pushed out by strong signals — so it damps the constant stimulation without blocking normal signal transmission.
Cholinesterase inhibitors boost the acetylcholine signal, which is too weak, and are licensed for mild to moderate Alzheimer’s dementia. Memantine damps down the excessive effect of glutamate and is licensed for moderate to severe dementia. This results in different stages of use and clearly different side effect profiles.
Memantine is mainly excreted unchanged via the kidneys. If the kidneys work less well, more of the drug stays in the body and the usual dose becomes too high. That is why kidney function is measured before starting, the dose is reduced if it is impaired, and it is checked regularly over time.
If the urine becomes more alkaline, the kidneys excrete less memantine and the drug level rises. Triggers can include a drastic switch to a purely plant-based diet, medicines that make the urine alkaline, baking soda for heartburn or certain urinary tract infections. Changes like these should therefore be discussed with a doctor.
The most common are dizziness, headache, sleepiness and constipation. A rise in blood pressure has also been described; occasionally, confusion temporarily increases at the start. Unlike with cholinesterase inhibitors, marked digestive complaints and a slowing of the heartbeat are not typical.
There is evidence of a favourable effect on behavioural symptoms such as restlessness and aggression, though the effect is moderate and develops over weeks. Looking for physical triggers such as pain or infections and non-drug measures take priority. In dementia, antipsychotics should be used only with restraint, at a low dose and for a limited time.
No. Memantine works on the symptoms and does not halt the progression of the disease. It can stabilise everyday abilities, cognitive performance and behavioural symptoms over a limited period, with a moderate effect on average and not noticeably in everyone.
Summary of Product Characteristics (SmPC) for memantine hydrochloride (current version, available through the German medicines information system). pharmnet-bund.de
German S3 guideline on dementia (DGPPN and DGN, AWMF reg. no. 038-013) — German source. awmf.org
Gesundheitsinformation.de (IQWiG): Alzheimer’s dementia — treatment with medicines. Accessed 2026 — German source. gesundheitsinformation.de
gesund.bund.de: Dementia — causes, diagnosis and treatment. Accessed 2026 — German source. gesund.bund.de
BfArM (German Federal Institute for Drugs and Medical Devices): drug and risk information on anti-dementia medicines and antipsychotics in older people. Accessed 2026 — German source. bfarm.de
Managing dementia medication together — with brite
Medication plan, reminders and interaction check for patients and their families. Free.
Medical disclaimer: This article is for general information and does not replace medical advice, diagnosis or treatment. Never stop memantine on your own and do not change the dose yourself — the right dose depends to a large extent on kidney function. With suddenly increasing confusion, severe dizziness, seizures or if the person stops drinking, contact a doctor straight away; with persistent unconsciousness, call 112 (emergency number in Germany). The choice of medicine and its dose is always decided individually by the treating practice. Last updated: September 2026.
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