Posted by undopaminergic on April 2, 2008, at 5:09:58
In reply to Re: Happy Ending :P - OCD/major depression/psychosis, posted by bleauberry on March 28, 2008, at 18:28:39
>
> The thing is, there was one case study done where a small group of depressed patients were given Memantine and not a single one of them got any benefit. So I think research and interest just isn't there.
>That's not quite true, because at least two other studies (one very recent) found potential benefit:
* An open-label, flexible-dose study of memantine in major depressive disorder.
http://www.ncbi.nlm.nih.gov/pubmed/17545748
* Double-Blind, Randomized Comparison of Memantine and Escitalopram for the Treatment of Major Depressive Disorder Comorbid With Alcohol Dependence.
http://www.ncbi.nlm.nih.gov/pubmed/18348597This may be the study you were referring to:
* A double-blind, placebo-controlled study of memantine in the treatment of major depression.
http://www.ncbi.nlm.nih.gov/pubmed/16390905
> I have often thought Memantine might have some unknown potential in psychiatry.
>You are not alone to think memantine (and many other "unproven" drugs) has potential. The problem is that it may be useful - perphaps tremendously so - only in certain patients, whereas it may be useless or even harmful for others. The standard approach of placebo controlled trials lumps a heterogenous group of people together under a diagnostic label such as "major depression", but the fact is that there are many subtypes of depression that differ in the underlying neurobiological etiology even though the overt symptoms may appear to be the same, and these subtypes require different approaches to treatment. Until this basic fact is acknowledged and accounted for, useful treatments (like memantine) will continue to be lost in the statistics.
> There is evidence that it prevents or reverses tolerance to opioids and stimulants. I sometimes wondered, if someone's own receptors are so tolerant of natural dopamine that the receptors don't work and leave the person depressed, maybe memantine could reverse that to normal? Purely hypothetical, but something I have pondered over the years.
>I've been thinking along those lines, too. It might be compared to diabetes type II, or tolerance to endogenous insulin: even though insuln levels may be elevated, a sufficient response can't be elicited because the receptors are desensitised. Analogously, even the high levels of dopamine produced by pharmacological interventions (stimulants, autoreceptor-antagonists, L-dopa, MAOIs, etc.) may fail to produce sufficiently strong neural signals due to some mechanism of tolerance or desensitation.
> I highly admire your prowess and determination. I mean, to come up with the idea of memantine, then to see a doc across the border in order to get it prescribed, and then to convince your home doctor to go along with it, well, that's pretty cool stuff. You can thank memantine all you want, but the real thanks go to yourself.
>The details may differ, but many - perhaps most - of us have been forced to develop and depend upon this kind of ambition and determination, because we don't have the assistance of resourceful doctors, friends, relatives, etc. For example, it may be necessary to order some medication from abroad because it's not approved locally, or because no doctor seems willing to write a prescription.
> One pilot study showed it was effective for post-heroin withdrawal depression and anhedonia. There is a syndrome after the acute withdrawal where patients enter a prolonged sustained withdrawal called "sustained anhedonia". Hmmm. Makes me wonder, how many other people here have that syndrome? I mean, maybe not caused from herion, but could be the same syndrome from some other reason. Seems to me I've seen it a lot. Anyway, memantine reversed it in a pilot study.
>Hypothetically, stimulation of kappa-opioid receptors by endogenous opioids may be the reason for such a syndrome.
I don't think it's just memantine, by the way, but perhaps NMDA-glutamatergic antagonists in general. There are very impressive reports on ketamine, for example. The glutamatergic release inhibition by lamotrigine and many other agents should also be considered in this context.
poster:undopaminergic
thread:820264
URL: http://www.dr-bob.org/babble/20080330/msgs/821118.html