![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 2 to 26 of 26. Go back in thread:
Posted by beardedlady on March 21, 2002, at 12:57:55
In reply to types of depression feelings, posted by JohnX2 on March 21, 2002, at 6:41:10
I think your depression feelings are typical: lack of interest in things you used to like to do, no motivation, impaired concentration. Sadness is the teary stuff.
A month ago, something somewhat bad happened to me, and I cried all the time. I told my pdoc I was so depressed I couldn't stand it, and then I said, "No, wait a minute. I'm not depressed. I'm sad. I'm very deeply sad."
I think there's a huge difference between the two, with sadness--the normal transient emotion--being the more emotional. Depression is such a constant state. Even when exciting, great, happy things happen, you're really unable to be joyous about them.
Maybe it's different for others, but that's been my experience.
beardy : )>
Posted by Penny on March 21, 2002, at 13:46:29
In reply to types of depression feelings, posted by JohnX2 on March 21, 2002, at 6:41:10
I would have to agree that my depression seldom feels like sadness. My grandfather died in November of last year and I was already going through a major depression, but then the sadness piled on top of it. But it was a teary sadness and, strangely enough, the depression seemed to lift somewhat (or the sadness took its place).
But the depression is in full force right now. I feel very empty. Lonely. Hopeless. Apathetic. Despondent. I don't cry a whole lot. Actually, I show a great deal more emotion when I have a major attack of anxiety. Then I might end up in a rage or in tears. But the depression...just sort of like a weight that I constantly carry on my shoulders. It seldom keeps me from doing the things I must, but it often keeps me from doing the things I want. And it's been going on for too long.
Penny
Posted by Janelle on March 21, 2002, at 15:28:37
In reply to types of depression feelings, posted by JohnX2 on March 21, 2002, at 6:41:10
Hi JohnX2 (what's the X2 for anyway?!!)
Yay - finally a chance to *help* you and respond to an issue that you raise - you are so helpful to me, that it is a pleasure to be able to answer a post that you put up!
First, I would ECHO exactly what beardedlady and Penny have both posted and stated so well.
As for my take on what you've said, when I get extremely depressed I also feel extremely empty and lose all ability to feel pleasure. I also think about death (suicide, though I'm too *chicken* to ever carry it out). I also get those bad feelings of worthlessness. HOWEVER, I do cry, sometimes it's major sobbing that I can't stop.
The feeling of SADNESS you describe, I've experienced those also and compared to DEPRESSION, sadness is a delight. I hate to use this word, but I would consider SADNESS to be *normal* and also healthy. Everyone experiences it, and it's usually in reaction to circumstances, e.g. death of a loved one, loss of a job, meaning it is ENVIRONMENTALLY induced.
Sometimes prolonged sadness (e.g., grief) can lead to depression (this happened to a relative of mine) - however, this kind of depression is ENVIRONMENTALLY induced and either responds to short term medication (this was the case for my relative) or lifts in a resonable amount of time.
Sadness and environmentally-induced depression aside, this leaves BIOCHEMICAL depression, which can also have a genetic component (runs in families). This is the most difficult depression to treat.
To answer your question, I think it varies from person to person in terms of the level of emotion depressed people feel and whether they get teary eyed or not. Since my depression comes with anxiety, I personally *do* get emotional and teary eyed.
Therefore, I would say that certain depressions/dx's (e.g. agitated depression, anxious depression) ARE prone to these symptoms, while other depressions are not - these depressions are like what you described - void of emotion, void of tears, basically void in general.
Best wishes
-Janelle
Posted by fachad on March 21, 2002, at 19:53:29
In reply to types of depression feelings, posted by JohnX2 on March 21, 2002, at 6:41:10
John,
I think that there are two factors that influence how much "sadness" vs. "emptiness" a person feels.
First, there is the acute depression vs. chronic depression issue.
I think that those lucky folk who go through life basically fine, then *wham* a Major Depression hits them, then it remits (with or without meds) and they are fine again and live happily ever after, tend to feel very severe SADNESS while they are depressed. Their episode(s) of depression are acute and severe.
This is in contrast to us unlucky folk whose depression is more constant and chronic. If you are depressed all the time, or for a long time, your psyche goes into some kind of self-protective analgesia.
Your nervous system is just not built to handle that much severe misery for so long, so it just kind of "shuts down" the irritating stimulus of painful sadness. That's where the numbness and emptiness come from.
The second factor that relates to the "sadness vs. emptiness" issue is post-medication brain changes. This is different from, but related to, the chronicity issue.
Most psych meds, and especially SSRIs, have an emotional anesthetizing effect. They are like Novocain for your painful neurons. That can be a good thing if you are suffering from severe sadness. But many people, myself included, who have taken them for a long time report blunted affect, apathy, numbness, etc. Those symptoms tend to persist, to a greater or lesser degree, even after the meds are stopped.
So either chronic depression or long-term exposure to psych meds, or more dramatically both, can shift a person from experiencing depression as sadness to experiencing it as numbness.
Just my take on it, anyway.
>
> When I get extremely depressed I just feel extremely empty and lose all ability to feel pleasure. Maybe if it is really bad I have obsessive thoughts about death. I also have really bad feelings of worthlessness. But I never cry or feel very emotional. I feel a void.
>
> Mild depression for me is of the atypical variety.
> Lack of motivation, interest, etc.
>
> Occasionally, but very seldom, I may feel "SAD". But this is something totally different that I hardly ever experience. Here I feel emotional and maybe a bit teary but I am not depressed. In fact, post "SAD" I usually feel good.
>
> Is this common for people. Or do most people who are depressed feel emotional and get teary eyed, etc? Are certain depressions/dx's prone to some symptoms over others?
>
> Just wondering.
>
> John
Posted by GB on March 21, 2002, at 21:56:26
In reply to types of depression feelings, posted by JohnX2 on March 21, 2002, at 6:41:10
Hey John,
I know I am out of depression when I can *CRY*. When depressed, like you, I am empty. You know what they say, the opposite of love is not hate, it is indifference! That is depression(indifference).
GB
Posted by pedr on March 22, 2002, at 8:43:21
In reply to Re: types of depression feelings » JohnX2, posted by Janelle on March 21, 2002, at 15:28:37
Janelle,
it's interesting to me that you say that sadness is a healthy emotion. Reason being that I'm doing REBT at the moment and it stresses the important difference between healthy emotions and unhealthy emotions:
sadness v.s. depression
annoyance/frustration v.s. anger
jealousy v.s. healthy desire
and so on.The main mechanism of REBT is to change your beliefs. The net result of doing this is that the unhealthy emotion you are experiencing [depression for me] changes to it's healthy version. I'm still in the mire of depression but I'm slowly beginning to see REBT's power when understood and employed properly.
That's all!
pete.
Posted by pedr on March 22, 2002, at 8:58:50
In reply to types of depression feelings, posted by JohnX2 on March 21, 2002, at 6:41:10
Hi John,
very interesting question. My depression manifests itself in several different ways:
- the sensation of being full causes me to feel intense self loathing. I've tried for many an hour to work this one out but am stumped. I very rarely eat a large meal as a result. When I do eat just too much [usually by accident] I then loath myself because I know it causes me to loath myself. Good grief.- what I call "biological depression". This is the undescribably vile feeling I get in my stomach, chest and heart with no associated thinking. There is nothing I can think/do/say/recall that shifts this bastard when it sets up camp. It's the most upsetting and demoralising of all my forms of depression and quickly makes me not want to be around. Thankfully of late it is less frequent.
- thinking based depression. This is where I can clearly see the link between a causal thought e.g. "I am worthless because I can't drink" or "I can't bear this work, it's so depressing" and the subsequent emotion. This is the type of depressed feeling that I stand a chance of combating with the REBT I do. I'm slowly making inroads into this... v e r y s l o w l y....
- social anxiety. This is where I have obsessive thoughts that people are thinking I'm a complete c*nt and so on. I've tried a million things to challenge this but it's resolute. It mainly makes me dread going on the tube and being on my own in public.
So there you go, a quick cross-section of my rather odd bonce.
Adios,
pete.
Posted by Elayne on March 22, 2002, at 10:12:11
In reply to depression feelings - sadness vs. emptiness » JohnX2, posted by fachad on March 21, 2002, at 19:53:29
To John,
My experience of depression is similar to yours.
To Fachad --
I was intrigued by your remark that this numbness or affective blunting is a commonly reported brain change that persists after meds are stopped. Is this something you've ever seen studied or is it something you've observed and experienced personally?
I personally have also experienced a change in anger (much less intense) and anxiety (not so phobic and shy) that has persisted even when off meds.
I don't miss the rage and fear. I do miss the ability to cry.
Anyone else notice changes in these areas post-meds?
Elayne
Posted by fachad on March 22, 2002, at 11:41:43
In reply to Re: sadness v emptiness and post-med brain changes » fachad, posted by Elayne on March 22, 2002, at 10:12:11
Elayne asked: "Is this something you've ever seen studied or is it something you've observed and experienced personally?"
Both. I was experiencing it personally, but it had developed so gradually that I did not notice it. The first place I saw it documented was actually here at the old "Psychopharmacology Tips" section of Dr. Bob's site back in 1995.
Here's the link to the discussion on SSRI induced Apathy:
http://www.dr-bob.org/tips/split/SSRIs-and-apathy.html
Anyway, after seeing the description, I was immediately able to see that that was what had happened to me.
My pdoc gave me methylphenidate and it reversed the apathy / lethargy. The reversal of the apathy also persisted after I stopped taking methylphenidate, so I know it was not just symptomatic treatment.
Since seeing the discussion here on “tips” so many years ago, I have now seen a few references in the literature to this problem. It seems to be an issue that the professional psychiatric community would rather not confront directly. It is not mentioned very frequently and not much space or detail is given to the discussion.
I cannot help but think that as more people are exposed to high dose SSRIs over long periods of time this complaint will become more and more prevalent, and will have to be addressed more seriously and systematically.
> To John,
>
> My experience of depression is similar to yours.
>
> To Fachad --
>
> I was intrigued by your remark that this numbness or affective blunting is a commonly reported brain change that persists after meds are stopped. Is this something you've ever seen studied or is it something you've observed and experienced personally?
>
> I personally have also experienced a change in anger (much less intense) and anxiety (not so phobic and shy) that has persisted even when off meds.
>
> I don't miss the rage and fear. I do miss the ability to cry.
>
> Anyone else notice changes in these areas post-meds?
>
> Elayne
Posted by Elayne on March 22, 2002, at 12:08:10
In reply to Re: sadness v emptiness and post-med brain changes » Elayne, posted by fachad on March 22, 2002, at 11:41:43
thanks for the link. Interesting stuff.
I have seen a number of references to SSRI-induced apathy, but haven't seen anything that acknowledges the persistence of this apathy even after the meds are stopped.
(In fact, not too long ago -- sorry I don't have the exact citation -- there was an anecdote about a psychiatrist who had started himself on Prozac when he went on vacation. He was doing well but decided it would be better to discontinue the drug when he caught himself thinking, as he listened to his patients, "Who cares?")
So I think that privately the psychiatric community has recognized the phenomenon of SSRI-induced apathy for many years. I believe you're right, that as more people have been treated for longer periods of time, the issue's going to be more obvious.
But what I haven't seen is discussion of permanent (or at least long-term) neurological changes that are manifested behaviorally as apathy and persist even in the absence of the drug -- the so-called "frontal lobe syndrome."
I find all this very troubling.
Elayne
Posted by BarbaraCat on March 24, 2002, at 0:52:06
In reply to Re: types of depression feelings » JohnX2, posted by Janelle on March 21, 2002, at 15:28:37
I agree with Janelle's post wholeheartedly about the environmental vs. biological. I used to call the worst of my symptoms 'depression', but I always cry hysterically and feel super sensitive and attuned to horrible negative world events and get frequent panic attacks. High stress will usually be the catalyst, but it's in my bio code. I've come to realize that I have a high anxiety component to the depression. 'Depression' has become such a catch-all term for the many varieties of neuro dysfunction. The anxiety kind needs to be given a different name cause it's so different from the anergic kind.
I also get the typical depression episodes where everything feels like moving through sludge and I lay the couch and feel dreary and empty. About the only emotion I can come up with is beating myself up about what a slug and failure I am. It's definitely different from the sobbing/axiety type. I'll tell you what, though, I'll take the slug kind over the wailing terrified kind any day.
Posted by BarbaraCat on March 24, 2002, at 1:07:53
In reply to depression feelings - sadness vs. emptiness » JohnX2, posted by fachad on March 21, 2002, at 19:53:29
You might want to give SAM-e a try. It helps with the blunting. I liked your insights on this topic, especially your 'novocaine for the brain' theory, and the protective emotional blunting statement.
I wonder what thoughts you'd have about someone (me) who has both kinds - the blunted dreary AND the severe major type - two very different symptomologies, but feeling very tied in to each other (the same illness but opposite poles). I don't have chronic dysphoria and have 6-7 month breaks of OK-ness (if I'm lucky) then 1-3 months of one or the other and sometimes both together of the sad vs. empty types. I've gone through just about every one of the newer AD's and my pdocs have all said that my profile is difficult to pin down.
Regards, Barbara
Posted by BarbaraCat on March 24, 2002, at 1:15:35
In reply to Re: sadness v emptiness and post-med brain changes » fachad, posted by Elayne on March 22, 2002, at 12:08:10
Elayne,
Talk some more about 'frontal lobe syndrome'. Is this an actual phenomenon that's being reported or researched? I worry about long term physical changes in receptor density and would be interested in any info where this is being addressed.Barbara
Posted by fachad on March 24, 2002, at 3:41:38
In reply to Re: depression feelings - sadness vs. emptiness » fachad, posted by BarbaraCat on March 24, 2002, at 1:07:53
BarbaraCat wrote: "I wonder what thoughts you'd have about someone (me) who has both kinds - the blunted dreary AND the severe major type - two very different symptomologies, ..."
Well, after I took Ritalin and a HUGE component of my depression resolved, I realized that there were actually (at least) two components to my depressive symptomologies.
First, there was the obvious "affective depression". That was the emotional sadness, etc. That "affective depression" responded very well to SSRIs.
Second, there was what I call "somatic depression", which consisted of lethargy, anergic, apathetic, physical dysphora, and general feeling of bodily yuckiness. This is what responds to psycho stimulants like Ritalin or Dexedrine.
The strange thing for me is that while SSRIs treat the affective depression, they worsen the somatic depression.
And for me, affective depression comes and goes, but the somatic depression is chronic.
So if the affective depression is really bad, I can take an SSRI until it is resolved, and then quit the SSRI.
But the somatic depression has always been there, way back when I was a teenager, and even as a pre-teen. (I'm in my mid-thirties now) And a course of SSRI treatment always makes it worse.
So pstims are my main treatment modality. I don't have to adjust dosage except after a course of SSRI's has increased the severity of the somatic depression. Ritalin definitely helps with the “blunting”.
For me, this whole distinction between affective and somatic depressions became evident when Ritalin was added. Medication response has been used before to define illness, so it wasn’t unprecedented in principle. I'd just never heard of that distinction in depressive symptoms before. But is sure has been an accurate and useful model for me.
> You might want to give SAM-e a try. It helps with the blunting. I liked your insights on this topic, especially your 'novocaine for the brain' theory, and the protective emotional blunting statement.
>
> I wonder what thoughts you'd have about someone (me) who has both kinds - the blunted dreary AND the severe major type - two very different symptomologies, but feeling very tied in to each other (the same illness but opposite poles). I don't have chronic dysphoria and have 6-7 month breaks of OK-ness (if I'm lucky) then 1-3 months of one or the other and sometimes both together of the sad vs. empty types. I've gone through just about every one of the newer AD's and my pdocs have all said that my profile is difficult to pin down.
> Regards, Barbara
Posted by JohnX2 on March 24, 2002, at 5:45:56
In reply to Frontal lobe syndrome » Elayne, posted by BarbaraCat on March 24, 2002, at 1:15:35
What is this frontal lobe syndrome?I saw this interesting pharmaceutical which they found by accident substantially reduces "emotional lability". So they are doing clinical trials for emotional lability in ALS patients. I was wondering if the same medication may be useful for emotional lability in psychiatry.
http://www.avanir.com/product/product.php?ID=3
http://www.mdausa.org/research/ct-alsdetro.html"The basic mechanisms underlying emotional control are unknown. Lesions in a variety of areas of the brain, including the frontal and temporal lobes, have been associated with the occurrence of pathological laughing and crying. Conceptually, it may be useful to think of pseudobulbar affect as an example of a disconnection syndrome which interrupts the normal integration of cortical and brain stem functions. This is a double-blind, controlled, randomized, national, multicenter clinical study. Patients who are eligible for the clinical trial will be in the study for one month. "
I initially was looking at it and thought it might help in the areas of medication tolerance development. I also saw possible applications in PTSD/BPD/atypical anxyiolytic/indirect CRF antagonist.
The guy who came up with this med idea was using it initially to treat addicts and also other fringe disorders like tinnitus and chronic cough.
John
> Elayne,
> Talk some more about 'frontal lobe syndrome'. Is this an actual phenomenon that's being reported or researched? I worry about long term physical changes in receptor density and would be interested in any info where this is being addressed.
>
> Barbara
Posted by Elayne on March 24, 2002, at 7:54:53
In reply to Frontal lobe syndrome » Elayne, posted by BarbaraCat on March 24, 2002, at 1:15:35
> Elayne,
> Talk some more about 'frontal lobe syndrome'. Is this an actual phenomenon that's being reported or researched? I worry about long term physical changes in receptor density and would be interested in any info where this is being addressed.
>
> BarbaraBarbara,
I was actually referring to the link in Fachad's post of 3/22 above:http://www.dr-bob.org/tips/split/SSRIs-and-
apathy.htmlBut I have seen this term used by others as well. Garland describes a "reversible frontal lobe (amotivational) syndrome ...characterized by apathy, indifference, loss of initiative and/or disinhibition" associated with SSRI use. Although she is talking about adolescents, the description is generalizable I think. (Brown University Child and Adolescent Psychopharmacology Update 3(10):1, 6-8, 2001).
Stephen Stahl, in Essential Psychopharmacology of Depression and Bipolar Disorder (2000), refers to SSRI-induced apathy as one of several undesirable side-effects that "...can be understood as undesirable actions of serotonin in undesirable pathways at undesirable receptor subtypes. This appears to be 'the cost of doing business,' as it is not possible for a systematically administered SSRI to act only at the desirable receptors in the desirable places." In this case he theorizes, "...stimulation of serotonin 2A receptors in mesocortical pleasure centers may reduce dopamine activity there and cause apathy...or decreased libido." (p.99)Notice that Garland is describing a REVERSIBLE phenomenon. And Stahl is talking hypothetically.
It's my impression that "frontal lobe syndrome" is a term used by neurologists to describe similar symptom clusters in people with known organic brain problems (e.g.,lesions, tumors, trauma). I think psychiatrists have borrowed the term and use it descriptively, even metaphorically, in trying to understand what they see. (I am no neuroscientist and would welcome correction or elaboration on this point).
I guess we all worry about long-term physical changes. I hope my posting didn't make you worry even more. I think knowledge in this area is really primitive in some ways.
For me, the issue comes back to a balance of risk and benefits and the ability to tolerate a lot of ambiguity.
Elayne
Posted by christophrejmc on March 24, 2002, at 12:08:18
In reply to Re: Frontal lobe syndrome » BarbaraCat, posted by JohnX2 on March 24, 2002, at 5:45:56
What is your take on NMDA antagonist neurotoxicity ("Olney's Lesions")? I could only find a few articles on MedLine, but I haven't looked too hard. Have you seen any reports of this with NMDA antagonist use? I believe it has been shown to happen with memantine/dextromethorphan/etc. As far as I know, it's only theoretically possible in humans, but it is kind of scary.
-chris
Posted by BarbaraCat on March 24, 2002, at 14:29:20
In reply to Multiple Layers of Depressive Symptoms » BarbaraCat, posted by fachad on March 24, 2002, at 3:41:38
Thanks, Fachad. I've heard of affective and somatic forms of depression before, but never made the connection as well as through reading your description. Here are some ideas to ponder. Do you think that this cycling between the affective and somatic forms is typical of 'depressive disorders'? When you go through the affective stage, acommpanied by tearfullness, are you also in the grip of an anxiety state?
I'm going to conjecture here, so hopefully you can stay with me and offer some comments. The opposite poles of somatic/affective seems to suggest that different neurochemicals come into play on an intermittant fluctuating basis. The anergic dysphoric phase suggests a lack of dopamine and/or NE. Theories state that there's a inverse relationship between serotonin and dopamine, so at the dysphoric times there is a disproportionate higher ratio of serotonin to the other more activating neurochems. That's probably why you'd feel much worse on an SSRI. Boosting the serotonin even more is going to create a minor serotonin syndrome, creating the body yucks worse inertia and generally awful feelings.
On the other hand, the affective stage suggests a lack of serotonin, thereby making dopamine more prominent, causing more lability and anxiety if one is so inclined. Of course, there's more involved here than just the three major players, but this flux in neurochemicals seems curious. Could it be affected and maintained by the meds we're taking? Perhaps SSRI's should be taken on a cyclical rather than constant basis to prevent the flat line effect which suggests that ooops! dopamine on the decline - better either cut back on the serotonin booster or take a pstim to prevent the see-sawing. Or, if dysphoric, just taking a pstim and then modifying as needed with an SSRI, as you are doing. I fortunately do not have chronic dysphoria, as you seem to, so my preference would be to take nothing until needed. Unfortunately, because my extremely severe episodes are mixed or all one or the other, I never know which way it's going to go and wouldn't have a clue as to how to tweak the med combo.
This fluctuating brain chemical bath idea has really grabbed my interest. If garden variety depression also typically has both affective and somatic elements, how different really is it than the bipolar disorders which may just be a matter of degrees. So perhaps this fluctuation property in itself needs to be looked at more closely. Are the mood stabilizers a big piece of the puzzle and perhaps even necessary if one is to 'get better'? Perhaps looking closer at balancing electro-chemical potential, resetting a magnetic/electrical switch (ECT, rTMS) makes more sense than manipulating chemicals which are always going to have a lag time in catching up to symptoms, and may even be contributing to and maintaining the whole dysfunction. I'm looking forward to the day when we all have a little portable brain zapper at home to align those little suckers as needed. - Barbara
Posted by JohnX2 on March 24, 2002, at 17:22:54
In reply to Re: NMDA antagonist neurotoxicity » JohnX2, posted by christophrejmc on March 24, 2002, at 12:08:18
I've seen reports of it happening with the more competitive antagonists. I haven't seen anything indicating that Memantine would cause an olney's lesion? Could you direct me to some info on that?
That medicine (memantine) has been in Germany for like 10 yrs+ and I don't think there has been case reports of Olney lesions from it.DXM (dextromethorphan) on the other hand is quite toxic at strong doses. That medication with dxm in it better monitor the blood levels very closely. I would be leary about the neurotoxicity, yes.
John
> What is your take on NMDA antagonist neurotoxicity ("Olney's Lesions")? I could only find a few articles on MedLine, but I haven't looked too hard. Have you seen any reports of this with NMDA antagonist use? I believe it has been shown to happen with memantine/dextromethorphan/etc. As far as I know, it's only theoretically possible in humans, but it is kind of scary.
>
> -chris
Posted by JohnX2 on March 24, 2002, at 17:41:56
In reply to Re: NMDA antagonist neurotoxicity » christophrejmc, posted by JohnX2 on March 24, 2002, at 17:22:54
I've read some papers by Olney.
I get confused by the theories surrounding schizopherenia. He suggests that it is caused by hypofunctional NMDA receptors. Also, he believes that 5ht-2a antagonists will exacerbate hypofunctioning NMDA receptors. He suggests in one paper I read using a 5ht-2a agonist to protect against NMDA antagonist (hypofunctioning) neurotoxicity. If this is the case, why do antipsychotic medicines block the 5ht-2a receptor?The neurotoxicity comes from regions of the brain where the NMDA receptors stimulate GABA neurons which in turn protect other neurons.
John
>
> I've seen reports of it happening with the more competitive antagonists. I haven't seen anything indicating that Memantine would cause an olney's lesion? Could you direct me to some info on that?
> That medicine (memantine) has been in Germany for like 10 yrs+ and I don't think there has been case reports of Olney lesions from it.
>
> DXM (dextromethorphan) on the other hand is quite toxic at strong doses. That medication with dxm in it better monitor the blood levels very closely. I would be leary about the neurotoxicity, yes.
>
> John
>
> > What is your take on NMDA antagonist neurotoxicity ("Olney's Lesions")? I could only find a few articles on MedLine, but I haven't looked too hard. Have you seen any reports of this with NMDA antagonist use? I believe it has been shown to happen with memantine/dextromethorphan/etc. As far as I know, it's only theoretically possible in humans, but it is kind of scary.
> >
> > -chris
Posted by christophrejmc on March 24, 2002, at 20:01:25
In reply to Re: NMDA antagonist neurotoxicity--christopherjmc, posted by JohnX2 on March 24, 2002, at 17:41:56
> I've read some papers by Olney.
> I get confused by the theories surrounding schizopherenia. He suggests that it is caused by hypofunctional NMDA receptors. Also, he believes that 5ht-2a antagonists will exacerbate hypofunctioning NMDA receptors. He suggests in one paper I read using a 5ht-2a agonist to protect against NMDA antagonist (hypofunctioning) neurotoxicity.> The neurotoxicity comes from regions of the brain where the NMDA receptors stimulate GABA neurons which in turn protect other neurons.
Is this the PCP-based schizophrenia hypothesis? That's a bit interesting... I wonder if he goes through with it. Are there any (clean) 5HT-2a agonists on the market? I've also read that certain anticholinergics can protect against NMDA antagonist neurotoxicity... Some people say that the midazolam(?) given with ketamine can also prevent neurotoxicity... Would it be naive of me to think this would have something to do with GABA -- if so, that might explain why other drugs that antagonize NMDA while also affecting GABA in various ways, would not be a problem...
> That medicine (memantine) has been in Germany for like 10 yrs+ and I don't think there has been case reports of Olney lesions from it.
s/memantine/amantadine/g. I think it was amantadine that I heard causing neurotoxicity... but I'm not sure how factual that claim is. The biggest offenders, in order, seem to be phencyclidine, [some drug Olney was working on], dextromethorphan, and ketamine.
I'm not sure how serious all of the cases are, and it's unlikely that they would perform an autopsy just for that...
Hmm.. time to do some more reading.
Thanks
-chris
Posted by JohnX2 on March 24, 2002, at 21:55:38
In reply to Re: NMDA antagonist neurotoxicity » JohnX2, posted by christophrejmc on March 24, 2002, at 20:01:25
> > I've read some papers by Olney.
> > I get confused by the theories surrounding schizopherenia. He suggests that it is caused by hypofunctional NMDA receptors. Also, he believes that 5ht-2a antagonists will exacerbate hypofunctioning NMDA receptors. He suggests in one paper I read using a 5ht-2a agonist to protect against NMDA antagonist (hypofunctioning) neurotoxicity.
>
> > The neurotoxicity comes from regions of the brain where the NMDA receptors stimulate GABA neurons which in turn protect other neurons.
>
> Is this the PCP-based schizophrenia hypothesis? That's a bit interesting... I wonder if he goes through with it. Are there any (clean) 5HT-2a agonists on the market? I've also read that certain anticholinergics can protect against NMDA antagonist neurotoxicity... Some people say that the midazolam(?) given with ketamine can also prevent neurotoxicity... Would it be naive of me to think this would have something to do with GABA -- if so, that might explain why other drugs that antagonize NMDA while also affecting GABA in various ways, would not be a problem...
>Yes, this was the PCP theory. The Gaba safeguard holds true.
> > That medicine (memantine) has been in Germany for like 10 yrs+ and I don't think there has been case reports of Olney lesions from it.
>
> s/memantine/amantadine/g. I think it was amantadine that I heard causing neurotoxicity... but I'm not sure how factual that claim is. The biggest offenders, in order, seem to be phencyclidine, [some drug Olney was working on], dextromethorphan, and ketamine.
>I believe memantine is quite safe. It is fairly non-competitive and just caps toxic hyper- glutamate transmission. Seems the others may be toxic at high doses. DXM is a non-competetive antagonist and is generally fairly safe else they wouldn't put it in cough syrup. It will be interesting to see how the Neurodex product with DXM makes it through FDA approval given the potential for toxicity.
There are a few patents by Olney discussing his thoughts on safe gaurding nmda hypofunctioning at www.upsto.gov
Patent 5,902,815 (use of 5-ht2a agonist)
Patent 5,605,911 (use of alpha-2 agonist)The alpha-2 agonist works on an acetylcholine pathway.
It seems a lot of people aren't in harmony on this pcp based theory of schizophrenia.
I don't know of 5ht-2a agonists in the market do you?
BTW, how is the Selegiline trial going?
Regards,
John> I'm not sure how serious all of the cases are, and it's unlikely that they would perform an autopsy just for that...
>
> Hmm.. time to do some more reading.
>
> Thanks
> -chris
Posted by christophrejmc on March 25, 2002, at 23:34:30
In reply to Re: NMDA antagonist neurotoxicity » christophrejmc, posted by JohnX2 on March 24, 2002, at 21:55:38
> It seems a lot of people aren't in harmony on this pcp based theory of schizophrenia.
Fer sure. It is interesting that the NMDA-antagonists induce both positive and negative symtpoms (or do the other psychotomimetic drugs do this as well?)... Perhaps this will lead to a novel treatment for the oft ignored negative/cognitive symptoms of schizophrenia.
There seems to be a dearth of information regarding neuroleptic-resistant schizophrenia. My psychiatrist (who spent a while practicing in one of our many long-gone (damn republicans!... sorry) psychiatric hospitals) told me that the hallucinations are often quite unresponsive to neuroleptic treatment.> BTW, how is the Selegiline trial going?
Slowly. I'm at 30mg now and am getting some mild, but annoying cardiovascular side effects. It's effects on mood are strange... slight elevation but with no blunted affect (I'm a chronic apathetic partial responder).
Are you still thinking about adding Li to your current regime? SLS's posts have me interested in trying low-dose Li. I didn't have any side effects for the one(!) day I was on it before.
Cheers,
Chris
Posted by BarbaraCat on March 26, 2002, at 1:00:58
In reply to Re: NMDA theory of schizophrenia, etc. » JohnX2, posted by christophrejmc on March 25, 2002, at 23:34:30
Chris,
I have responded to a small dose (300 mg) of Lithium like a textbook's dream. All AD's have pooped out and I've been on all of them. Finally agreed to augment with Lithium and the Remeron that had died kicked in like gangbusters within the first week. This was in the midst of a suicidal depression.I've gained weight, both from the Remeron and the Li, but now I'm getting a life again and am starting to resume exercising. Don't know what your dx is but just wanted to inform you of one grateful Lithium customer. - BCat
Posted by JohnX2 on March 26, 2002, at 2:58:01
In reply to Re: NMDA theory of schizophrenia, etc. » JohnX2, posted by christophrejmc on March 25, 2002, at 23:34:30
> > It seems a lot of people aren't in harmony on this pcp based theory of schizophrenia.
>
> Fer sure. It is interesting that the NMDA-antagonists induce both positive and negative symtpoms (or do the other psychotomimetic drugs do this as well?)... Perhaps this will lead to a novel treatment for the oft ignored negative/cognitive symptoms of schizophrenia.
>
> There seems to be a dearth of information regarding neuroleptic-resistant schizophrenia. My psychiatrist (who spent a while practicing in one of our many long-gone (damn republicans!... sorry) psychiatric hospitals) told me that the hallucinations are often quite unresponsive to neuroleptic treatment.
>
> > BTW, how is the Selegiline trial going?
>
> Slowly. I'm at 30mg now and am getting some mild, but annoying cardiovascular side effects. It's effects on mood are strange... slight elevation but with no blunted affect (I'm a chronic apathetic partial responder).
>
> Are you still thinking about adding Li to your current regime? SLS's posts have me interested in trying low-dose Li. I didn't have any side effects for the one(!) day I was on it before.
>
Yes, I am probably going to do the Li trial this week. I am too unstable and out of mood stabilizer options. I could try to push my Lamictal dose, but this has caused problems in the past. The Li trial is quick as most people feel an effect rapidly, so I may as well give it a go + I feel I likely need a low dose.I would like to try Acamprosate or Memantine as atypical mood stabilizers and to help with a dystonia, but it may be a hard sell with my pdoc. I'm more into these natural compounds like Acamprosate (a taurine derivative) or neuroprotective meds (Memantine). I once tried taking a low dose dxm concurrent with Wellbutrin and I was able to get a sustained Wellbutrin response without tinnitus or headache or poopout, but I aborted the crazy experiment as the dxm half life was too short and required crazy dosing plus it could be toxic (although I wasn't hallucinating or anything). You need for a CYP2d6 inhibitor as in the Neurodex med to make this dxm a feasable medicine. It was amusing, but a silly thing to do. I also get poop out on amphetamines, so I thought the nmda antagonist medicines may be interesting for me to try (memantine being a safe one, acamprosate too).
Take care.
John
> Cheers,
> Chris
This is the end of the thread.
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