Memantine is a moderate-affinity, uncompetitive NMDA receptor antagonist indicated for moderate-to-severe Alzheimer's disease. It is the only approved Alzheimer's drug with a non-cholinergic mechanism and is often used in combination with donepezil. It provides modest improvements in cognition, daily function, and behavioral symptoms.
Severe renal impairment without dose adjustment6,7
The bottom line
Evidence rating moderate. Most-documented uses: slows cognitive and functional decline in moderate-to-severe ad, synergistic benefit when combined with cholinesterase inhibitors, may improve behavioral symptoms (agitation, aggression). 10 sources indexed (2018–2025), with 1 interaction record on file.
The science
How it works, mechanistically.
Core mechanism
Blocks pathologically activated NMDA receptors by binding to the ion channel in a voltage-dependent manner, reducing excessive glutamatergic excitotoxicity that contributes to neuronal damage in Alzheimer's disease. At therapeutic concentrations, it preferentially blocks tonically active (extrasynaptic) NMDA receptors while preserving physiologic phasic synaptic transmission necessary for learning and memory.
Class
NMDA Antagonist / Alzheimer's
Dosing
Dosing & protocol.
Common range
5 mg once daily initially, increased by 5 mg/week to target of 10 mg twice daily (immediate-release) or 28 mg once daily (extended-release) (as prescribed by your physician)
Recommended form
Extended-release capsule (Namenda XR 28 mg) for once-daily dosing; immediate-release tablets or oral solution also available
Well absorbed with ~100% bioavailability; food does not affect absorption. Dose adjustment needed for severe renal impairment (CrCl 5-29 mL/min: max 5 mg BID).
A controlled human study found that combining memantine with alcohol increased dissociation, confusion, stimulation, and impaired balance without changing alcohol pharmacokinetics. Because memantine is commonly used in people with cognitive impairment or fall risk, alcohol can make confusion, dizziness, judgment impairment, and injury risk more clinically important.
Recommendation: Avoid or minimize alcohol while taking memantine, especially during titration, in older adults, or when dementia symptoms, dizziness, or fall risk are present. Do not drive or do safety-sensitive tasks after drinking. Seek medical advice for new severe confusion, agitation, falls, fainting, or unsafe behavior.
Zhang W, Zhang Y, Yu E. Effectiveness and Safety of Memantine Add-on Treatment for Refractory Obsessive-Compulsive Disorder: A Meta-Analysis. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2025
Choi WS, Wang SM, Woo YS et al.. Therapeutic Efficacy and Safety of Memantine for Children and Adults With ADHD With a Focus on Glutamate-Dopamine Regulation: A Systematic Review. The Journal of clinical psychiatry. 2024
Nair A, Dudhedia U, Thakre M et al.. Efficacy of memantine premedication in alleviating postoperative pain- A systematic review and meta-analysis. Saudi journal of anaesthesia. 2024
Turalde CWR, Espiritu AI, Anlacan VMM. Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials. Frontiers in neurology. 2020
Zheng W, Li XH, Yang XH et al.. Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials. Psychological medicine. 2018
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