Psycho-Babble Medication Thread 383680

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Re: A possible explaination. » linkadge

Posted by owensmar on August 29, 2004, at 17:18:01

In reply to A possible explaination., posted by linkadge on August 29, 2004, at 16:33:58

> What you are saying is very true. Dopamine itself is not the magic pleasure chemical. What we do know is that activation of the D3 receptors (which are loaded in the nucleus accumbens which is supposedly one of the pleasure centers in the brain) seems to improve anhedonia fairly reliably.


Please tell me how to activate the D-3 receptors. Do low doses of the dopamine antagonists (as in the previous post) do this? Or do you need a dopamine agonist instead?

Anhedonia is such a severe problem for me. I feel that my life is wasting away while I sit on the couch, unable to find pleasure or reward in anything at all.

I am on Effexor xr 37.5 mg day (low dose because of side effects & medication sensitivity).

The only time I feel pleasure or motivation to engage in any activty is when I have taken hydrocodone. That drug seems to turn on the reward center in my brain and makes even unpleasurable tasks (doing my taxes) fun. (I severely limit my use of this drug, though, figuring it probably makes the problem worse in the long run.)

If I could experience pleasure in normal, everyday life, well, then, I'd actually have a life - instead of an existence.

Hopefully awaiting the answer to all my problems,

Marsha

> But boosting dopamine in other areas of the brain can cause apathy, dark moods, paranoia, guilt, jealousy, anger, grandiosity, and other strange states of the human condition.
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> Anyhow, one theory that I heard is that neuroleptics *can* increase pleasure by blocking some of the bad dopamine regions and allowing more dopamine to reach pleasure centers (ie d3 receptors)
>
> I have found this too. If I take ritalin or coffee then I am oftentimes anhedonic, but neuroleptics seem to improve anhedonia. Stimulants plus neuroleptics can enhance the anti-anhedonic effect (but the combination is way too funky for me !!!)
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> Linkadge
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Re: A possible explaination. » linkadge

Posted by Maximus on August 29, 2004, at 17:23:30

In reply to A possible explaination., posted by linkadge on August 29, 2004, at 16:33:58

That is a very good explanation and résumé indeed. Thanks a million!

We seem to share a lot of symptoms together.

Anyway i don't remember exactly what you're taking as medication. But if you're still taking a SSRI + an atypical antipsychotic and you still need energy (antidepressive response), then Lamictal might be another golden key for your problems. It doesn't touch the usual neuro-transmitters.

Good luck!

 

Re: A possible explaination. » owensmar

Posted by Maximus on August 29, 2004, at 17:35:38

In reply to Re: A possible explaination. » linkadge, posted by owensmar on August 29, 2004, at 17:18:01

> Please tell me how to activate the D-3 receptors. Do low doses of the dopamine antagonists (as in the previous post) do this? Or do you need a dopamine agonist instead?

Hi there,

I can partially answer to you. Pramipexole (Mirapex) is a D3 receptor agonist. It has been proven effective in treatment-resistant depression.

However it has also some drawbacks. Anger, rage and hyperactivity have also been reported as side effects.

Good luck!

 

Re: A possible explaination.

Posted by linkadge on August 29, 2004, at 18:05:54

In reply to Re: A possible explaination. » owensmar, posted by Maximus on August 29, 2004, at 17:35:38

"I can partially answer to you. Pramipexole (Mirapex) is a D3 receptor agonist. It has been proven effective in treatment-resistant depression. However it has also some drawbacks. Anger, rage and hyperactivity have also been reported as side effects."

Mirapex also activates the D2 receptor a little less potently than the D3. This *may* be more responsible for those side effects than the d3 receptor activation.

Personally I think a golden antidepressant combo would be this. Buspar and mirapex. Buspar would be the serotonin agonist at the 5-ht1a receptor and provide antidepressant activity here, as well, mirapex would hit the d3 receptors. As a bonus, the buspars d2 antagonism would block some of the mirapex's d2 receptor agonism, and perhaps some of these side effects.

Linkadge


 

Re: A possible explaination. » owensmar

Posted by linkadge on August 29, 2004, at 18:12:35

In reply to Re: A possible explaination. » linkadge, posted by owensmar on August 29, 2004, at 17:18:01

You could try a drug like mirapex, which would hit the d3 receptor directly, or try an atypical, which may indirectly hit this receptor. An even better combo might be an atypical plus mirapex.

Another thing to consider is trying exercising. I know it sounds like something you need motivation for to start but consider this: One study ( will try to find) showed that 45 min of aerobic exercise daily increased the expression and afinity for the d3 receptor. Ie the dopamine that dose get to it would be much more effective.

I think that exercise and mirapex would be a good combination.

Linkadge

 

Re: A possible explaination.

Posted by linkadge on August 29, 2004, at 18:34:18

In reply to Re: A possible explaination. » owensmar, posted by linkadge on August 29, 2004, at 18:12:35

I tend to think of the d3 activation as the "personal pleasure". I have a feeling that it makes pleasure seem very "personal" and "your own", and "complete/satisfying".

I think that actiavtion of other dopamine receptors *can* increase pleasure but they tend to give that feeling of "uncompleteness", or "wanting more". That feeling of being good, but its "not yours", or its "just out of reach".

This is of course pure speculation, but I have formulated some hunches based on the combo's I've tried. The AP's like seroquel/zyprexa 'low dose'
imroved anhedonia and make pleasure seem more complete and personal, while the stimulants seemed to make thinks more *interesting* but gave that aweful pressured feeling. Its hard to describe but its like "to much is given much is expected" Perhaps its just an extension of my mild psychosis :) but stimulants tend to make me feel more 'universally responsable' and 'guilty'.

The d2 receptor is highly involved in psychosis
I think that d2 activation can create that deep feeling of presence, almost making things 'super real'. I think it can boost feelings of significance, making your actions feel more significant and important. It can bring meaning to your life, but sometimes too much meaning or imagined created meaning. I think that d2 activation is too deep for me.

I think that d1 activation is more involved in feelings of creating logical order. It activates parts of the brain that seek structure order symmetry etc. I think that d1 activation brings pleasure from completion.

Again this is certainly not set in stone, but this is some of the ideas I have conjured from some of the reading I have done.

I found seroquel the best of the 3 AP's. It doesn't block the d1 receptor like zyprexa does and left me more motivated. Zyprexa didn't leave me apathetic, but just "unmotivated".


Linkadge


 

Re: A possible explaination. » linkadge

Posted by zeugma on August 29, 2004, at 18:59:34

In reply to Re: A possible explaination., posted by linkadge on August 29, 2004, at 18:34:18

The d2 receptor is highly involved in psychosis
I think that d2 activation can create that deep feeling of presence, almost making things 'super real'. I think it can boost feelings of significance, making your actions feel more significant and important. It can bring meaning to your life, but sometimes too much meaning or imagined created meaning. I think that d2 activation is too deep for me.

I think that d1 activation is more involved in feelings of creating logical order. It activates parts of the brain that seek structure order symmetry etc. I think that d1 activation brings pleasure from completion>>

This is fascinating. One of the symptoms of my ADHD that I found most destructive, and that even my therapist who is a professional specializing in the study of ADHD, found confounding: the dysphoria that would follow on completing *anything*. I literally would feel awful after finishing a task, not because it exhausted me, and not because I was anhedonic, because I could still derive pleasure from 'random' occurences. But completion, of anything, and I wanted to crawl into a hole and shut myself off from the world.

Since starting stimulants that work on DA receptors, I have begun to look forward to finishing things, because completion doesn't bring this dysphoria.

-z

 

Re: A possible explaination. » linkadge

Posted by owensmar on August 29, 2004, at 20:19:29

In reply to Re: A possible explaination., posted by linkadge on August 29, 2004, at 18:34:18

First off, thank you for your considered and in depth analysis. I so often feel no one can even understand what I am talking about, let alone make suggestions to improve it.

> I tend to think of the d3 activation as the "personal pleasure". I have a feeling that it makes pleasure seem very "personal" and "your own", and "complete/satisfying".

I gather from this that the atypicals are D1 and D2 antagonists, whereas Mirapex is a D3 agonist. Does this mean that the atypicals somehow downregulate the (too many?) dopamine receptors making what little dopamine you have more available/active?

> I think that actiavtion of other dopamine receptors *can* increase pleasure but they tend to give that feeling of "uncompleteness", or "wanting more". That feeling of being good, but its "not yours", or its "just out of reach".

Are you talking about the atypicals here?

What about amilsulpride?

> This is of course pure speculation, but I have formulated some hunches based on the combo's I've tried. The AP's like seroquel/zyprexa 'low dose'
> imroved anhedonia and make pleasure seem more complete and personal, while the stimulants seemed to make thinks more *interesting* but gave that aweful pressured feeling. Its hard to describe but its like "to much is given much is expected" Perhaps its just an extension of my mild psychosis :) but stimulants tend to make me feel more 'universally responsable' and 'guilty'.

Stimulants (ritalin, provigil, phentermine)make me feel wired and world weary at the same time. Like I've taken a barbiturate and drunk a pot of coffee at the same time. Is this what you mean? Physical energy but nothing worthwhile to do with it - no mental/emotional kick to go with the physical part.

> The d2 receptor is highly involved in psychosis
> I think that d2 activation can create that deep feeling of presence, almost making things 'super real'. I think it can boost feelings of significance, making your actions feel more significant and important. It can bring meaning to your life, but sometimes too much meaning or imagined created meaning. I think that d2 activation is too deep for me.

Do antagonists activate? It sounds like that's what you're saying. ARe you talking here again about the atypicals?


>
> I found seroquel the best of the 3 AP's. It doesn't block the d1 receptor like zyprexa does and left me more motivated. Zyprexa didn't leave me apathetic, but just "unmotivated".

Okay, Zyprexa blocks the d1 receptor, it's an antagonist. It blocks without stimulating - that's the definition of an antagonist, right? But Seroquel blocks the D-2 and D-3 receptors?

I don't understand. HOw is it that blocking (without stimulating) the receptors can increase dopamine activity? I understand how an agonist can increase activity; I don't understand how an antagonist does it.

I promise I am not unintelligent. I have only recently begun to research this stuff when I figured out that no p-doc was going to do it on my behalf.

Another thing for me to think about is that I have galactorrhea (breasts produce small amounts of fluid). I have read that this can be due to dopamine depleting agents (or to a pituitary tumor called a prolactinoma). However, since the galactorrhea started when I started on a/ds in 1986 I wonder whether the increased serotonergic and/or norepineprinergic (is that even a word) receptor activity has somehow caused the dopamine receptors to inactivate or go into hiding, as it were. That would explain my anhedonia - which actually seems to be worse on Effexor. I feel very little on Effexor, can't cry, don't feel grief, etc. as well as not feeling joy or pleasure.(Admittedly I would rather be anhedonic than weeping constantly and imagining possible suicide scenarios.) AT least I think so.

I am printing out all three of your posts (since I can't view them simultaneously and it's too much information fo rme to process at once)to try and understand better. I wonder if I dare take them with me to my appointment with my new P-doc on Thursday...

Thank you so much,

Marsha

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Re: A possible explaination. » linkadge

Posted by owensmar on August 29, 2004, at 20:30:48

In reply to Re: A possible explaination., posted by linkadge on August 29, 2004, at 18:34:18

And Linkadge, do you then then an ssri or snri is a bad choice for me? ssri's in general give me muscle tension resulting in chronic pain and also cause anxiety. I take Effexor because it doesn't have that side effect but it does seem to be terribly enervating as opposed to the ssri's. I was thinking of asking for a trial of Cymbalta on the theory that my low dose of Effexor might not be therapeutic but with Cymbalta's supposedly more clean se profile, I could take a therapeutic dose and the world would be lovely again.

The last time I remember feeling almost normal was when I was on imipramine in 1986-87. I even thought of asking for a trial of that, "dirty" as it is.

I am sorry to ask so many questions.

Marsha

 

Re: A possible explaination. » owensmar

Posted by King Vultan on August 29, 2004, at 22:50:20

In reply to Re: A possible explaination. » linkadge, posted by owensmar on August 29, 2004, at 20:19:29


>
> Another thing for me to think about is that I have galactorrhea (breasts produce small amounts of fluid). I have read that this can be due to dopamine depleting agents (or to a pituitary tumor called a prolactinoma). However, since the galactorrhea started when I started on a/ds in 1986 I wonder whether the increased serotonergic and/or norepineprinergic (is that even a word) receptor activity has somehow caused the dopamine receptors to inactivate or go into hiding, as it were. That would explain my anhedonia - which actually seems to be worse on Effexor. I feel very little on Effexor, can't cry, don't feel grief, etc. as well as not feeling joy or pleasure.(Admittedly I would rather be anhedonic than weeping constantly and imagining possible suicide scenarios.) AT least I think so.
>
>


Good try, but "noradrenergic" is the term that seems to be used to refer to norepineprinergic type activity. The term is derived from noradrenaline, which is another word for norepinephrine; likewise, adrenaline and epinephrine are the same thing, giving rise to the analogous term "adrenergic".

If you're on a low dose of Effexor, the effect is almost all serotonergic, which may tend to further deplete dopamine in the pleasure centers of the brain. I also noticed the emotional aloofness on Effexor you describe and would recommend trying something that has a more powerful effect on norepinephrine. This seems to be the neurotransmitter that is most involved with feeling deep emotion, spirituality, and empathy. Well, that's been my experience, anyway.

Todd

 

Re: A possible explaination.

Posted by linkadge on August 30, 2004, at 15:38:36

In reply to Re: A possible explaination. » linkadge, posted by owensmar on August 29, 2004, at 20:19:29

By blocking one dopamine receptor, you actually leave more dopamine to hit other receptors - or so I've been told.

So a d1 d2 antagonist, would probablty result in more d3 d4 activation etc.

Linkadge

 

Re: A possible explaination.

Posted by linkadge on August 30, 2004, at 15:42:57

In reply to Re: A possible explaination. » owensmar, posted by King Vultan on August 29, 2004, at 22:50:20

Well, like the tryciclics, effexor causes adaptive changes in the dopamine d2/d3 systemts. It actually increases their responsivness. This change takes a while and is generally why anhedonia is the last and often most difficult symtpom to ameliorate. You could try adding some wellbutrin, a stimulant or dopamine agonist to try and improve the anhedonia.


Linkadge

 

Re: A possible explaination.

Posted by owensmar on August 30, 2004, at 19:01:28

In reply to Re: A possible explaination., posted by linkadge on August 30, 2004, at 15:38:36

> By blocking one dopamine receptor, you actually leave more dopamine to hit other receptors - or so I've been told.
>
> So a d1 d2 antagonist, would probablty result in more d3 d4 activation etc.
>
> Linkadge

Aha! Figured that out last night after some puzzling. So it's just a question of doing it directly or indirectly. And whether one is better able to tolerate an atypical or a drug like mirapex!

Thank you.

Marsha

 

Re: A possible explaination.

Posted by owensmar on August 30, 2004, at 19:03:41

In reply to Re: A possible explaination., posted by linkadge on August 30, 2004, at 15:42:57

> Well, like the tryciclics, effexor causes adaptive changes in the dopamine d2/d3 systemts. It actually increases their responsivness. This change takes a while and is generally why anhedonia is the last and often most difficult symtpom to ameliorate. You could try adding some wellbutrin, a stimulant or dopamine agonist to try and improve the anhedonia.
>
Linkadge, if you don't mind my asking, how do you know all this stuff? Have you just had to educate yourself as a survival mechanism (as I'm doing) or are you in the sciences?

Marsha
> Linkadge

 

Re: Role of Dopamine in anhedonia?(chemist, linkadge) » Maximus

Posted by jerrympls on August 30, 2004, at 19:11:10

In reply to Role of Dopamine in anhedonia?(chemist, linkadge), posted by Maximus on August 29, 2004, at 13:19:50

> Hi there,
>
> I was wondering how dopamine plays in anhedonia.
>
> To make a long story short, when i take a dopamine agonist like Ritalin, i feel stoned, more detached.
>
> But actually i'm taking Seroquel, a dopamine antagonist, and i feel more alive, more empathetic. I would say that Seroquel awakens something, somewhere in the brain.
>
> Any theories?
>
> Thanks!

Weird - Seroquel blunted all my pleasure centers....stimulants do the opposite...
Jerry

 

Re: A possible explaination. » King Vultan

Posted by owensmar on August 31, 2004, at 11:04:18

In reply to Re: A possible explaination. » owensmar, posted by King Vultan on August 29, 2004, at 22:50:20

Yeah, that's kind of why I had hopes for Cymbalta. If it does turn out to have a really clean se profile then maybe I could take a therapeutic dose and the NE thing would kick in. And then maybe I could add a dopamine agonist or antagonist -- then I'd be hitting on all three.
Marsha

 

Re: A possible explaination. » owensmar

Posted by linkadge on August 31, 2004, at 17:05:14

In reply to Re: A possible explaination., posted by owensmar on August 30, 2004, at 19:03:41

I've just done a lot of reading from the site www.biopsychiarty.com/refs. This site is loaded with various research abstracts on various drugs.

Linkadge

 

To Linkadge, King Vultan

Posted by 4WD on September 4, 2004, at 21:32:09

In reply to Re: A possible explaination. » owensmar, posted by linkadge on August 31, 2004, at 17:05:14

I forgot to thank you for all the info on dopamine receptors and the various drugs that can affect them. I was able to go to my new Pdoc appointment with some idea of what I wanted to say and with the vocabulary to say it with. It would have taken me weeks to search all this out on the net.

Thanks again,

Marsha

 

Re: Role of Dopamine in anhedonia?(chemist, linkadge)

Posted by sailor on October 1, 2004, at 12:02:27

In reply to Re: Role of Dopamine in anhedonia?(chemist, linkadge), posted by zuzu80 on August 29, 2004, at 14:24:14

ZUZU 80--I am very interested in beginning a trial of amisulpride. After hours of webcrawling, I am unable to find a source. I see that it was once marketed as Solian, but now seems to be out of production by that lab and since picked up by Sterwin Medecines. But the Sterwin website makes no mention of it (?). I'm at an apparent dead end for now. If you would e-mail me at brionkerlin@yahoo.com I would be grateful. Regards, Sailor

 

Re: A possible explaination. » linkadge

Posted by iris2 on October 1, 2004, at 17:32:30

In reply to Re: A possible explaination., posted by linkadge on August 29, 2004, at 18:05:54

Do you think Mirapex could be substituted for Amisulpride? Kind of a strange way to put it.

Would they potentially have the same effect?

irene

 

Re: A possible explaination.

Posted by linkadge on October 2, 2004, at 8:31:24

In reply to Re: A possible explaination. » linkadge, posted by iris2 on October 1, 2004, at 17:32:30

In this case *no*. Amisulpride potently blocks the d2 (but more importantly blocks the d3) receptors. Mirapex on the other hand is a potent d2/d3 agonist.

Mirapex would probably be much better at treating anhedonia (at least theoretically)

The only time atypicals can be good at treating anhendonia is when they are potent d2 blockers but *don't* block the d3 receptor. In this case the blocked dopamine makes its way to the d1/d3 receptors which can help anhedonia.


The only other factor to consider is where the drugs block the receptors. My above assesment is assuming that the drugs block all dopamine receptors throughout the body. Some antipsychotic are preferetial to say lower brainstem dopamine receptors and leave the ones in the nucleus accumbens (pleasure centres) open. So in practice the only way is trial and error. But there is a better chance that mirapex would activate the NAA (neucleus accumbens) and give that reward.


Linkadge

 

Re: A possible explaination. » linkadge

Posted by jerrympls on October 2, 2004, at 11:12:09

In reply to Re: A possible explaination., posted by linkadge on October 2, 2004, at 8:31:24

> In this case *no*. Amisulpride potently blocks the d2 (but more importantly blocks the d3) receptors. Mirapex on the other hand is a potent d2/d3 agonist.
>
> Mirapex would probably be much better at treating anhedonia (at least theoretically)
>
> The only time atypicals can be good at treating anhendonia is when they are potent d2 blockers but *don't* block the d3 receptor. In this case the blocked dopamine makes its way to the d1/d3 receptors which can help anhedonia.
>
>
> The only other factor to consider is where the drugs block the receptors. My above assesment is assuming that the drugs block all dopamine receptors throughout the body. Some antipsychotic are preferetial to say lower brainstem dopamine receptors and leave the ones in the nucleus accumbens (pleasure centres) open. So in practice the only way is trial and error. But there is a better chance that mirapex would activate the NAA (neucleus accumbens) and give that reward.
>
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> Linkadge
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I've been suffering from anhedonia a chronic dysthymia for years. I've been trying to convince doctor after doctor that it's my dopamine/reward centers that are out of whack. Well, about 10 days ago I was diagnosed with Restless Legs Syndrome (RLS) and was put on .125mg of Mirapex with directions to double the dose after a week or so. This past Tuesday I doubled the dose and felt greater relief from the RLS, but I also noticed that I've been more interested in actually *doing* things - talking to friends, cleaning my apt (!), listening to music, working on some computer web projects, etc. All stuff I *had* enjoyed before anhedonia set in years ago. Today's the 3rd day I've felt an increase in motivation, etc., and it's feels good. I can only hope it continues to last!!

 

Re: A possible explaination. » linkadge

Posted by iris2 on October 2, 2004, at 14:32:05

In reply to Re: A possible explaination., posted by linkadge on October 2, 2004, at 8:31:24

This is difficult as that is a major symptom yet I find I do feel better on Amisulpride. I do not think I whold take them together?

irene

 

Re: A possible explaination. » iris2

Posted by iris2 on October 2, 2004, at 22:53:12

In reply to Re: A possible explaination. » linkadge, posted by iris2 on October 2, 2004, at 14:32:05

Linkage,

Based upon what you have suggested I am thinking I should stop taking the Amisulpride and try Mirapex. But the Amisulpride is helping with the depression but nothing for the anhedonia.

Perhaps since I have so much trouble finding any med I can tolerate I should stay on the Amisulpride and add Strattera?

I was going to add Cymbalta but I am not sure I will be able to take it because of bladder disease. I am also having high prolactin from the Amisulpride. My periods stopped and I had it tested.

Too much for my small mind to wrap itself around. I need help.

This is a plea!

irene

 

Low dose Geodon for dopamine

Posted by MoparFan91 on April 8, 2005, at 17:36:18

In reply to Re: A possible explaination. » iris2, posted by iris2 on October 2, 2004, at 22:53:12

I'm currently taking 20mg of Geodon per day (10mg 2xday). Since taking it, I seem to have more motivation, better focus, and more concentration. I also seem to have more interest in things, and I feel more fulfillment from accomplishments as well. I'm more confident as well, and I seek out more things. However, I also take things somewhat harder, and I get mad a little more easily.

The Geodon at that dose feels more like a very mild version of speed. I feel more alert in the mornings and less foggy during the day. It's also easier to get going in the morning.

Like other antipsychotics like amisulpride, does low dose Geodon preferentially block the presynaptic dopamine receptors indirectly causing an increase in dopamine transmission?

My doctor told me that Geodon acts more like a dopamine agonist at very low doses.

When I was at higher doses of Geodon (over 40mg/day), I had the opposite effects. I had effects such as ADHD symptoms, can't focus worth crap, apathy, zombified state, EPS, loss of memory. I think I got these effects because the higher doses block all dopamine receptors.


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