![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 23 of 23. This is the beginning of the thread.
Posted by g_g_g_unit on May 12, 2009, at 2:51:25
i have a concern which was sparked by a meeting with my GP today, in which i informed him that i was trialing Memantine. he said that i did not seem to present the characteristics of glutamate overactivity (which would conventionally call for him to prescribe Neurontin); if anything, given my persistent anhedonia, faltering memory, etc. he thought it might be a case of the opposite. i realise memantine's status as a partial antagonist means that it only activitates in the face of potential exitotocity, but does that also mean itgoes some way towards restoring homoeostasis in an underactive glutamate system?
or would it be best combined with an extraneous stimulant (glycine, piracetam, etc.)?
Posted by SLS on May 12, 2009, at 6:28:18
In reply to memantine for anhedonia?, posted by g_g_g_unit on May 12, 2009, at 2:51:25
> i have a concern which was sparked by a meeting with my GP today, in which i informed him that i was trialing Memantine. he said that i did not seem to present the characteristics of glutamate overactivity
How does he determine this?
> (which would conventionally call for him to prescribe Neurontin);
Or, and especially, Lamictal.
> if anything, given my persistent anhedonia, faltering memory, etc. he thought it might be a case of the opposite.
Are you bipolar?
I am not sure that memantine by itself is helpful for anhedonia. I know that lamotrigine is. As I am now taking memantine for nearly 4 weeks, I believe that I am benefiting from it, but anhedonia is not among the symptoms that it is helping with. I have more energy and motivation, and some improvement in cognitive impairment.
I am trying to sell the idea to my doctor that a three-pronged attack against hyperglutamatergic activity would include:
1. lamotrigine: GLU release inhibition
2. memantine: GLU (NMDA) receptor antagonism
3. topiramate: GLU (AMPA/kainite) receptor antagonism.Each drug operates on glutamatergic neurotransmission through distinctly different mechanisms.
By the way, how does gabapentin act as an antiglutamatergic?
Thanks.
- Scott
Posted by g_g_g_unit on May 12, 2009, at 9:15:26
In reply to Re: memantine for anhedonia? » g_g_g_unit, posted by SLS on May 12, 2009, at 6:28:18
note: i am only repeating what i was told (and admittedly took with a grain of salt) so don't shoot the messenger. he also, i should add, has nothing to do with my memantine trial, which is being conducted by a psychiatrist who has very little experience with the drug either (at least outside of treating Alzheimer's), and is going ahead based on research OCD-related research i sent him when pushing to trial the drug
> How does he determine this?he said glutamate hyperactivity might be a state more common in PTSD or schizophrenia where one literally experiences overactive imprinting, i.e. floods of unpleasant images, etc
>
> > (which would conventionally call for him to prescribe Neurontin);
>
> Or, and especially, Lamictal.
>
> > if anything, given my persistent anhedonia, faltering memory, etc. he thought it might be a case of the opposite.
>
> Are you bipolar?not as far as i know.
>
> I am not sure that memantine by itself is helpful for anhedonia. I know that lamotrigine is. As I am now taking memantine for nearly 4 weeks, I believe that I am benefiting from it, but anhedonia is not among the symptoms that it is helping with. I have more energy and motivation, and some improvement in cognitive impairment.motivation i could certainly do with; ditto cognitive improvement. my plan was too combine memantine with some kind of stimulant (since i feel like DA might also be an issue) - either DLPA/N-acetyl-tyrosine and/or a 'racetam and maybe even a small dose of st john's wort - though once he determined glutamate hyperactivity might not be an issue (a theory which i have a feeling you're going to hopefully discount), i suddenly become confused.
i realise that attributing essentialist characteristics to certain neurotransmitters is way too simplistic in terms of diagnosis, but does glutamate hyperactivity/underactivity generally present itself in clusters of recurring symptoms? what made you pursue the glutamate angle?
>
> I am trying to sell the idea to my doctor that a three-pronged attack against hyperglutamatergic activity would include:
>
> 1. lamotrigine: GLU release inhibition
> 2. memantine: GLU (NMDA) receptor antagonism
> 3. topiramate: GLU (AMPA/kainite) receptor antagonism.
>
> Each drug operates on glutamatergic neurotransmission through distinctly different mechanisms.
>
> By the way, how does gabapentin act as an antiglutamatergic?i have no idea.
>
> Thanks.
>
>
> - Scott
Posted by SLS on May 12, 2009, at 21:19:01
In reply to Re: memantine for anhedonia?, posted by g_g_g_unit on May 12, 2009, at 9:15:26
> what made you pursue the glutamate angle?
- Lamotrigine helps me.
- Topamax helps me.
- Provigil hurts me.
- Glutamate inhibition in the thalamus results in an increase in dopaminergic activity in the nucleus accumbens (the reward/feel-good center).As I see it here, I guess it is possible for memantine to improve anhedonia.
What dosage of memantine are you using now, and how high are you willing to go with it?
Currently:
Parnate 80mg
nortriptyline 150mg
Lamictal 200mg
Abilify 20mg
memantine 20mg.
- Scott
Posted by g_g_g_unit on May 12, 2009, at 22:48:17
In reply to Re: memantine for anhedonia?, posted by SLS on May 12, 2009, at 21:19:01
i began taking 5mg three days ago.
so far: day 1 + 2 no noticeable effect aside from a worsening of short-term memory (i.e. might make a mental note to look at so-and-so website, then forget seconds later), as well as (more troubling)these slight, uncontrollable head twitches which seem to arise most frequently during conversation. it's hard to tell if i actually am twitching, or if it's just a feeling, but either way certain movements don't feel smooth or continuous. the memory doesn't bother me as i read that memantine has an antagonistic effect on nicotine receptors, to which tolerance develops extremely quickly (2-3 days).
re: day 3, it may just be a placebo effect, but one sensation i get is the feeling that i'm somehow more 'present'; i've been listening to one of my favourite albums today, and it's almost like the sounds have begun to take on a more obvious texture - like i'm almost hearing them for the first time. sorry if that sounds more quasi-poetic than anything, but it makes sense, given that, in my depressive/OC ruminative states, i spend so much time dwelling on my own thoughts etc. that i often lose grasp of the reality of things.
i'm willing to at least achieve my target therapeutic dose of 20mg, and, pending that fails, move up to 30mg.
Posted by Sigismund on May 13, 2009, at 16:03:44
In reply to memantine for anhedonia?, posted by g_g_g_unit on May 12, 2009, at 2:51:25
>or would it be best combined with an extraneous stimulant (glycine, piracetam, etc.)?
I'm guessing you mean glutamine rather than glycine?
You sleep OK on memantine?
It's very long acting.
Maybe higher doses do not interfere with sleep any more than lower doses?
Posted by g_g_g_unit on May 13, 2009, at 17:18:04
In reply to Re: memantine for anhedonia? » g_g_g_unit, posted by Sigismund on May 13, 2009, at 16:03:44
> I'm guessing you mean glutamine rather than glycine?sorry, yeah glutamine
>
> You sleep OK on memantine?so far so good, though i'm using bacopa as a sleeping/memory aid
>
> It's very long acting.
>
> Maybe higher doses do not interfere with sleep any more than lower doses?did you find that memantine caused insomnia for you?
Posted by Sigismund on May 13, 2009, at 18:59:09
In reply to Re: memantine for anhedonia?, posted by g_g_g_unit on May 13, 2009, at 17:18:04
Just about anything causes insomnia for me. Bacopa, rhodiola and deprenyl did. I rather liked bacopa though. Mostly the things I like make insomnia worse. Lately I have had some success combining a gramme of tryptophan with 3 of glycine for if I wake in the night. I only ever took 1 memantine tablet. I have more just waiting around. Now that the wretched agomelatine I ordered and paid for has disappeared into a bureaucratic black hole, I have the opportunity to experiment.
Posted by g_g_g_unit on May 13, 2009, at 21:16:35
In reply to Re: memantine for anhedonia? » g_g_g_unit, posted by Sigismund on May 13, 2009, at 18:59:09
i'd definitely be interested in hearing your experience. from my understanding, memantine seems to operate according to a bell-curve, so that one needs to achieve an optimum level of NDMA inhbition without further impairing memory, learning, etc. i guess i just a bit thrown by my GP's comment, since neither i nor my pdoc actually considered whether i might be over/underactive, though after uncovering the symptoms of the latter (i.e. negative schizophrenic) i'm pretty sure i don't fit the mold; i can emote, think, etc. relatively well. the problems i'm having are more to do with a diminished sense of rward, less ability to react spontaneously (i.e. during converations with strangers), difficulty focusing my attention, so i'm guessing it's more a DA or NE issue
Posted by Sigismund on May 14, 2009, at 0:56:46
In reply to Re: memantine for anhedonia?, posted by g_g_g_unit on May 13, 2009, at 21:16:35
>i can emote, think, etc. relatively well.
I dunno anything about negative schizphrenic symptoms, but you sound OK on that score.
>the problems i'm having are more to do with a diminished sense of reward, less ability to react spontaneously (i.e. during converations with strangers), difficulty focusing my attentionYes, well. I can't even help myself with any of that. That was why I started using opiates. I could act spontaneously at last. You know, you're driving along and there's a watermelon stall and you want one. But how do you know how to make the decision to stop and buy one?
>so i'm guessing it's more a DA or NE issueMaybe. I have no idea.
Posted by g_g_g_unit on May 14, 2009, at 3:01:56
In reply to Re: memantine for anhedonia?, posted by Sigismund on May 14, 2009, at 0:56:46
what opiates are you taking? i guess memantine could be ideal since it also supposedly prevents opiate tolerance.
i recall you mentioning you were taking hydergine? are you still on it at the moment? i'm really interested in trying it, but a little scared off by the fibrosis reports
Posted by Sigismund on May 14, 2009, at 4:30:04
In reply to Re: memantine for anhedonia?, posted by g_g_g_unit on May 14, 2009, at 3:01:56
>what opiates are you taking? i guess memantine could be ideal since it also supposedly prevents opiate tolerance.
Yes, that's something to think about. There are (frankly to me) unbelievable stories about giving up methadone with memantine. The 'I forgot to take my dose' sort of thing. But I'm not taking any opiates at the moment.
>i recall you mentioning you were taking hydergine? are you still on it at the moment?Not right now. I take 400mg SAMe in the morning and hope for the best.
>i'm really interested in trying it, but a little scared off by the fibrosis reportsI had not heard about that. Nothing to do with ergot derivatives and heart valves?
Posted by g_g_g_unit on May 14, 2009, at 4:52:48
In reply to Re: memantine for anhedonia?, posted by Sigismund on May 14, 2009, at 4:30:04
>
> >i'm really interested in trying it, but a little scared off by the fibrosis reports
>
> I had not heard about that. Nothing to do with ergot derivatives and heart valves?looks like it: http://www.imminst.org/forum/index.php?showtopic=19023
what made you stop? insomnia? were the cognitive benefits easily observable?
Posted by Sigismund on May 14, 2009, at 16:07:32
In reply to Re: memantine for anhedonia?, posted by g_g_g_unit on May 14, 2009, at 4:52:48
Insomnia was not a problem with Hydergine because I took 4.5 or 9mg under the tongue first thing.
Generally it has just tended to have a positive effect on my mental state.
But not always, which is why I stopped.
I have it around and will use it again probably.
Posted by Amelia_in_StPaul on May 19, 2009, at 12:16:14
In reply to Re: memantine for anhedonia?, posted by g_g_g_unit on May 12, 2009, at 9:15:26
Hey there, can I butt in? I have OCD and PTSD--images do literally imprint on my memory (as do sounds, thoughts). I am not schizophrenic, but I do have these other conditions (and speaking as someone whose sister has schizophrenia, you definitely do not have negative symptoms). So I'm trying to follow your line of discussion. Does this mean Memantine (Namenda) might work, as well as Lamictal and Neurontonin? And that Provigil probably wouldn't? I am seeing a new pdoc thurs and want to have an idea of what to ask for. Many thanks, Amelia
> note: i am only repeating what i was told (and admittedly took with a grain of salt) so don't shoot the messenger. he also, i should add, has nothing to do with my memantine trial, which is being conducted by a psychiatrist who has very little experience with the drug either (at least outside of treating Alzheimer's), and is going ahead based on research OCD-related research i sent him when pushing to trial the drug
>
>
> > How does he determine this?
>
> he said glutamate hyperactivity might be a state more common in PTSD or schizophrenia where one literally experiences overactive imprinting, i.e. floods of unpleasant images, etc
>
> >
> > > (which would conventionally call for him to prescribe Neurontin);
> >
> > Or, and especially, Lamictal.
> >
> > > if anything, given my persistent anhedonia, faltering memory, etc. he thought it might be a case of the opposite.
> >
> > Are you bipolar?
>
> not as far as i know.
> >
> > I am not sure that memantine by itself is helpful for anhedonia. I know that lamotrigine is. As I am now taking memantine for nearly 4 weeks, I believe that I am benefiting from it, but anhedonia is not among the symptoms that it is helping with. I have more energy and motivation, and some improvement in cognitive impairment.
>
> motivation i could certainly do with; ditto cognitive improvement. my plan was too combine memantine with some kind of stimulant (since i feel like DA might also be an issue) - either DLPA/N-acetyl-tyrosine and/or a 'racetam and maybe even a small dose of st john's wort - though once he determined glutamate hyperactivity might not be an issue (a theory which i have a feeling you're going to hopefully discount), i suddenly become confused.
>
> i realise that attributing essentialist characteristics to certain neurotransmitters is way too simplistic in terms of diagnosis, but does glutamate hyperactivity/underactivity generally present itself in clusters of recurring symptoms? what made you pursue the glutamate angle?
>
> >
> > I am trying to sell the idea to my doctor that a three-pronged attack against hyperglutamatergic activity would include:
> >
> > 1. lamotrigine: GLU release inhibition
> > 2. memantine: GLU (NMDA) receptor antagonism
> > 3. topiramate: GLU (AMPA/kainite) receptor antagonism.
> >
> > Each drug operates on glutamatergic neurotransmission through distinctly different mechanisms.
> >
> > By the way, how does gabapentin act as an antiglutamatergic?
>
> i have no idea.
>
> >
> > Thanks.
> >
> >
> > - Scott
>
>
>
Posted by g_g_g_unit on May 19, 2009, at 19:58:13
In reply to Please, quick explanation? » g_g_g_unit, posted by Amelia_in_StPaul on May 19, 2009, at 12:16:14
well, from my understanding, Memantine is a partial NDMA antagonist, which means it helps to put a cap on any excessive glutamate activity, and thus help prevent neurotoxicity from glutamate overexcitation. what i'm curious about though is whether it's possible to just diagnose glutamate over or underactivity at a glance like that (my psychiatrist admits that he can't).
it's true in the past that i would often 'overimprint' - i.e. be able to recall the smallest, most inane details from stuff, commit entire essays to memory during college etc. it's literally like my brain was going too quickly. but after coming off anti-depressants, i experienced the opposite problem; my brain felt completely empty, i was incapable of expressing emotion, etc. so does that mean SSRI's - or withdrawal, at least - will downregulate glutamate?
my worry was in introducing Memantine when i felt like that, because i was wondering how it would act in someone who theoretically had low glutamate activity? after coming off Nardil, i definitely feel a lot more emotionally present, though still mentally fatiged. however, the more i'm off anti-depressants, the more i can feel brain activity, as well as my OCD, making a return, so i guess my natural state must be one of glutamate overactivation. then again my memory sucks, and i can't really hold on to new stuff that i learn. so i don't really know. the picture's probably way more complicated that i realise. but i'm guessing that Memantine will hopeuflly make me better sooner than worse. i'm on my 3rd day @ 10mg, and aside from a feeling of slight confusion/memory loss (which i believe to be transient) i'm already reaping some benefits (though not neecessarily in the OCD department at this tage).
at a guess it sounds like you might be someone who would benefact similarly. are you taking anything else at the moment?
> Hey there, can I butt in? I have OCD and PTSD--images do literally imprint on my memory (as do sounds, thoughts). I am not schizophrenic, but I do have these other conditions (and speaking as someone whose sister has schizophrenia, you definitely do not have negative symptoms). So I'm trying to follow your line of discussion. Does this mean Memantine (Namenda) might work, as well as Lamictal and Neurontonin? And that Provigil probably wouldn't? I am seeing a new pdoc thurs and want to have an idea of what to ask for. Many thanks, Amelia
Posted by desolationrower on May 20, 2009, at 18:42:13
In reply to Re: Please, quick explanation?, posted by g_g_g_unit on May 19, 2009, at 19:58:13
actually nmda overactivity is more likely to be excitotoxcic and thus destroy the relevant synapse
its not a partial agonist, its a low-affinity voltage-dependent uncompetitive nmda antagonist with fast-off kinetics. if you want a better explanation, look at this document:: http://www.isnvalladolid.org/pdfs/LiptonMemantineNRDD_SL.pdf
it has nice pictures and everything. memantine.com is an unusually useful site for a pharm manufactuerer. probably because its 'merz' some german company.
btw, nmda antaonism is probably how magnesium and zinc improve antidepressant response. they aren't as strong as memantine, but most people are deficient, and they help things like blood pressure too.
-d/r
Posted by g_g_g_unit on May 20, 2009, at 22:29:57
In reply to Re: Please, quick explanation?, posted by desolationrower on May 20, 2009, at 18:42:13
> its not a partial agonist, its a low-affinity voltage-dependent uncompetitive nmda antagonist with fast-off kinetics. if you want a better explanation, look at this document:: http://www.isnvalladolid.org/pdfs/LiptonMemantineNRDD_SL.pdf
>
> it has nice pictures and everything. memantine.com is an unusually useful site for a pharm manufactuerer. probably because its 'merz' some german company.
>
> btw, nmda antaonism is probably how magnesium and zinc improve antidepressant response. they aren't as strong as memantine, but most people are deficient, and they help things like blood pressure too.
>
> -d/ri don't think i called an agonist did i? anyway, i think i found out the answer to my question: low glutamate activity may just as likely be the result of downregulation - following chronic glutamate overactivity - as a phenomenon in and of itself. in which case the introduction of memantine would be useful, since by putting a cap on glutamate excess, it would allow the receptors to begin to upregulate, thus restoring normal glutamate activity.
d/r are you taking the drug at the moment? i've been taking it for 10 days, 3 days @ 10mg. so far, so mixed. main problem is the impact it's having on my short-term memory, which is in fact making my attention span worse, though i believe it shows its full benefits re: cognition only following chronic use at a therapeutic dose?
Posted by desolationrower on May 21, 2009, at 4:36:28
In reply to Re: Please, quick explanation?, posted by g_g_g_unit on May 20, 2009, at 22:29:57
> i don't think i called an agonist did i? anyway, i think i found out the answer to my question: low glutamate activity may just as likely be the result of downregulation - following chronic glutamate overactivity - as a phenomenon in and of itself. in which case the introduction of memantine would be useful, since by putting a cap on glutamate excess, it would allow the receptors to begin to upregulate, thus restoring normal glutamate activity.
>
> d/r are you taking the drug at the moment? i've been taking it for 10 days, 3 days @ 10mg. so far, so mixed. main problem is the impact it's having on my short-term memory, which is in fact making my attention span worse, though i believe it shows its full benefits re: cognition only following chronic use at a therapeutic dose?
>
>did you read the study i posted? theres some more out there, its more complicated than just receptor up/down regulation.
i went to 20mg and stopped, i didn't notice a strong benefit and since i lost my job needed to save all the $ i could
if you're noticing fogginess i'd say wait that out before you increase the dose again.
-d/r
-d/r
Posted by g_g_g_unit on May 21, 2009, at 6:05:55
In reply to Re: Please, quick explanation?, posted by desolationrower on May 21, 2009, at 4:36:28
certain facets of my cognition have improved, but yeah short-term memory's a pain. interesting to see it's impact on ocd as well, because with a suffering working memory i am more likely to engage in ruminations/compulsions, given that the neutralizing effect those actions have ends up rather short lived. i'll try and get through that study you posted to get a better understanding of the drug's mechanism. browsing through mindandmuscle's archives, i came across one poster who theorized that the initial fogginess might be accounted for by the drug's antagonist effect on nACHr - an effect which the brain grows desensitized to extremely quickly (hence the necessity for longer time periods to see the drug's full effect, as well as why the drug performed poorly in single-dose trials on healthy subjects).
i guess i am just a bit worried because i am sick of trying to figure out what's wrong with my brain; memantine was meant to be my final shot at at least achieving baseline (i.e. being able to hold down a job i enjoy). i also just feel kinda down in general, which can no doubt be pegged to only having being off Nardil for about 2 weeks.
Posted by g_g_g_unit on May 22, 2009, at 0:46:47
In reply to Re: Please, quick explanation?, posted by g_g_g_unit on May 21, 2009, at 6:05:55
just putting these questions out there - no urgency, so feel free to respond at will - but one problem i'm noticing on memantine is an increase in addictive behaviours (surfing the net, spending money, etc.) which had all but come to a halt during my depression. obviously on some level i take this as a good sign, but does that kind of response to an increase in dopamine(at least that's what i'm assuming is at stake) mean that there's also some kind of SE/DA imbalance at hand?
Posted by desolationrower on May 22, 2009, at 15:29:03
In reply to Re: Please, quick explanation?, posted by g_g_g_unit on May 22, 2009, at 0:46:47
I'm not sure how it does this. but its a common finding for effective antidepressant treatments.
-d/r
Posted by g_g_g_unit on May 25, 2009, at 10:07:08
In reply to Re: Please, quick explanation?, posted by desolationrower on May 22, 2009, at 15:29:03
well, i have been trying to find dosing guidelines and it's proving really difficult (mainly because my pdoc doesn't know anything about the drug, and most pharmacists are hesitant about advising regarding off-label; i even rang the company directly and couldn't get much out of them).
when i said the drug was increasing addictive behaviours, there wasn't much pleasure or euphoria behind it; it was more like a hard-edged stimulation that was in its own way inhibiting concentration because my mind felt like it was working too quickly (i.e. non-selectively imprinting detail etc.). i couldn't work out whether (as a sign of too much D2) that meant i should lower or raise the dose; i was wondering if the drug's D2 action is maybe more predominant at lower doses and then the NMDA effect kind of overtakes and begins to modulate it at higher doses? but then i realised that due to the 60(?) hour half-life i probably also haven't achieved a steady blood plasma level. was it you d/r who in another thread reported that the drug has an early amphetamine effect which soon fades?
anyway, i am wondering now whether i should try splitting the 10mg between morning and night and see if i can get some benefit from that, once the more stimulating effect (hopefully) fades. otherwise if higher doses prove to be more calming, it would probably be worth pushing to 20mg, and sitting it out until i had a steady blood plasma level. it's just that now that i'm beginning to finally see some benefits (the drug has completely vanquished the brain fog that's plagued me for the past year, and which had left me pretty much unemployed) i'm starting to get impatient, though i know i shouldn't rush it. this is just such a huge breakthrough for me that i don't wanna mess it up ..
This is the end of the thread.
Psycho-Babble Neurotransmitters | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.