Memantine vs Cholinesterase Inhibitors for AD question

[cyrushanleone]

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Hey, sorry if this sounds like a really stupid question but I thought this would be the ideal place to ask this question for clarification. So uptodate seems to say for mild to moderate Alzheimer's Disease (MMSE < 26) a trial of cholinesterase inhibitors should be initiated and memantine is only added on if it is moderate-advanced Alzheimer's (MMSE < 17). However, I was looking at some sources that claimed that Memantine might potentially be disease-modifying. If that is the case, would it not be reasonable to start someone off with a trial of memantine instead of a cholinesterase inhibitor? What is the reason we don't start someone off with memantine first? Memantine's side effect profile does not look concerning at all. Are they both equally efficacious in improving cognition?

 

[freelow_per7]

cyrushanleone, excuse the late response.
You are right that more recent studies show Memantine may be more beneficial than previously thought in treating earlier stages of cognitive impairment.
However, Donepezil's benefits of delaying disease progression in the milder stages is not up for debate.
I guess if someone presented with advanced Alzheimer's Dementia, it really wouldn't matter whether you started Aricept, Namenda, or the combination first.
However, my decision in clinic is easy. I don't go through all the trouble.
I still typically start patients on Donepezil. Why? because unless your patient has commercial insurance or is wealthy, 9/10 times they won't be willing to pay out of pocket for Namenda or Namzaric.

 

[neglect]

1. Memantine is on generic, so price now is less of an issue.
2. Everyone should know about Forrest Lab's forced switch. This was highly disruptive, screwed the patients that Forrest pretended to serve, and Namenda XR offers nothing new of value. The company also did no other R&D.
3. Memantine is an NMDA receptor medication. NMDA receptors have a strongly intuitive role in cognition as coincidence detectors (they feel both neurotransmitters outside the cell and the state of the cell: depolarized or not). While Memantine may block a bit of Ca++ from getting into the cell, this is NOT neuroprotective. It seems much more likely that Memantine modulates the NMDA to make the neuron more sensitive to proper communication. This seems to have a symptomatic benefit, but it is small, and @cyrushanleone, is only seen at moderate to severe disease. Forrest is such a bad actor that they marketed the drug off label, and many, @freelow_per7, may have taken the bait.
4. Again @freelow_per7, Aricept has no disease modifying effect. So when you say delays disease progression, this is actually highly controversial. Thal et al showed there was no change in MCI to AD with or without Aricept. This makes me very strongly think that it is not a DMT.
5. I like to start Namenda with a firm target in mind: better neuropsych control.

 

[freelow_per7]

Neglect, thanks for chiming in. I service a mostly geriatric and highly educated population (mostly Medicare). In clinical practice, a significant amount of my patients do in-fact appear to respond well to AChEIs if the diagnosis is made correctly and promptly. You are right, ultimately Aricept will not stop disease progression, but I have no doubt it may slow the progression of symptoms in a subset of patients. I have personally had patients d/c Aricept thinking it was ineffective only to have significant deterioration on d/c'ing. I try to explain to my patients that none of these medications are miracle pills. I state the facts and leave the decision up to the patient. I find that most people, given the alternate, are willing to grab on to a "modest" benefit.

I use Namenda as well for behavioral control in the severe stages of the disease. However, I am hesitant to start early on unless the patient could not tolerate AChEIs.