Memantine

Memantine is used to treat moderate to severe Alzheimer's disease. It acts on the glutamatergic system by blocking NMDA receptors.

• Memantine is indicated for the treatment of patients with moderate to severe Alzheimer's (i.e. - the MMSE score must be < 20).^[1]
• There is also some evidence for use in mixed, vascular, Parkinsons's disease dementia, and dementia with Lewy bodies.

• Glutamate is the main excitatory neurotransmitter in the brain, and binds to the NMDA receptor in the brain.
  • Excessive glutamate release leads to excitotoxicity, which is thought to be a major mechanism of neurodegeneration in ischemia from stroke, trauma from traumatic brain injuries, and neurodegenerative disorders.
  • However, glutamatergic transmission also important for long-term potentiation, and this is a proposed cellular model for learning and memory
• Memantine is a non-competitive NMDA receptor antagonist that is thought to help prevent excitotoxicity (mediated by Ca2+)
• Memantine blocks NMDA receptors and so may reduce the negative effects of glutamate, namely the excitotoxicity pathway via NMDA receptor over-activation, which is thought to prevent cell death.
• Memantine may also be neuroprotective.

• Week 1: 5 mg PO qAM
• Week 2: 5 mg PO BID
• Week 3: 10 mg PO qAM and 5mg PO qHS
• Week 4: 10 mg PO BID

• Dose should be halved in patients with renal impairment.^[2]
  • CrCl < 50: no dose adjustment required, but close monitoring recommended
  • CrCl < 30: max 5 mg BID
  • CrCl < 15: avoid

• Use with caution in patients with severe hepatic or renal impairment

• Memantine is generally well tolerated. Most common side effects may include insomnia, diarrhea, urinary incontinence, constipation, hypertension, confusion, dizziness, or agitation.
• Memantine though not as effective, is much better tolerated than acetylcholinesterase inhibitors

• No major drug interactions.