Memantine
An Alzheimer’s medicine that blocks the NMDA receptor. Added to antipsychotics, it improved negative symptoms in small trials.
At a glance
- Type
- Medicine: NMDA receptor blocker
- Used for
- Tested as an add-on for negative symptoms and thinking problems in schizophrenia
- Status
- Experimental, approved in Europe for Alzheimer’s disease
- Evidence
- EmergingHow evidence is rated
- Administration
- Tablets, once a day, added to an antipsychotic
- In Europe
- Available in Europe for Alzheimer’s disease. A Danish trial in first-episode psychosis ended in 2025
Clinical summaryFor health professionals
- Memantine blocks NMDA receptors; approved in the EU for moderate to severe Alzheimer's disease (EMA).
- Meta-analysis, 13 trials, 681 patients (Hong 2025): moderate to large improvement in negative symptoms; improvement in cognition; no clear effect on positive symptoms.
- No more fatigue, dizziness, headache, nausea or constipation than placebo (Kishi 2017); no excess dropouts (Zheng 2018).
What it is
Memantine blocks the NMDA receptor for glutamate. In Europe, it is approved for moderate to severe Alzheimer’s disease.1 In schizophrenia, it has been tested as an add-on to antipsychotics for negative symptoms, such as low motivation and withdrawal, and for problems with thinking, which antipsychotics barely improve.2
Blocking the NMDA receptor may seem the wrong direction, since a weak NMDA receptor is thought to contribute to schizophrenia, as explained in Beyond dopamine (opens in a new tab). How memantine helps, if it does, is not known.
How well it works
Pooled across 13 small trials with 681 people, memantine improved negative symptoms moderately to markedly, and improved thinking skills; hallucinations and delusions did not clearly change.2 An earlier analysis of 8 trials found the same for negative symptoms.3 In a network analysis of people whose illness had not responded to earlier treatment, clozapine combined with memantine did better than clozapine alone.4 The trials were small and differed from one another.2
Side effects
In the trials, fatigue, dizziness, headache, nausea and constipation were no more common than on placebo, and people did not stop more often.5,3
Alternatives
Other medicines aimed at the NMDA receptor include sodium benzoate (opens in a new tab) and D-serine and sarcosine (opens in a new tab). For negative symptoms, psychological and social treatments are part of standard care.
What we don’t know yet
- Whether the benefit holds in a large trial.
- How a medicine that blocks the NMDA receptor eases symptoms thought to come partly from a weak NMDA receptor.
