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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 34. This is the beginning of the thread.
Posted by SLS on April 9, 2009, at 8:10:25
Yes, I have heard for years that SSRIs cause dopamine depletion, and that this might be responsible for the induction of apathy/amotivation/anhedonia or a loss of therapeutic effect ("poop-out"). However, where is there scientific evidence to support this notion? I would say that chronic SSRI usage might produce a change in the activity of neural pathways afferent to dopaminergic structures and circuits. However, to think that neurons actually run out of neurotransmitter seems unlikely to me. They probably are just not being stimulated to release the dopamine that they keep in storage.
What do you think? Is there any scientific evidence that demonstrates that an SSRI can produce dopamine depletion downstream?
- Scott
Posted by shasling on April 9, 2009, at 8:44:15
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
I had a ton of abstracts which involed very small studies of groups of students.
What they found was amazing,it sure wasnt a simple sero deficiency.Instead when comparing depressed to non depressed particapants there were TONS of differental values.
Some i remeber were major excitatory amino acid to inhibtory ones all showed deficencys in those of depressed patients.
Alpha comming waves were all off.Major nutrients were all over.
Brain grey matter was off.
and the list went on and on and on showing the obvious when your brain isnt working properly one can only guess the deficanys that will arise from that,this is why i personaly dont value selective drugs over drugs such as maois which basicaly have a huge therputic window.
Posted by garnet71 on April 9, 2009, at 9:19:00
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
I'd be very intersted to know too. But just because there is no scientific evidence doesn't mean something does not exist. (just stating the obvious/what everyone already knows) Everything (ex-causations) proved by science over the past 50 years didn't really 'exist' before then? What about evidence from clinical practice? We all see how the methodology of many studies are flawed, funded by drug companies (and negative studies hidden in relation to # of positive ones), or maybe it is not possible yet to set up a study to determine certain things. I think sometimes in medicine, science doesn't necessarily translate to efficiacy in practice. And theory, even with scientific evidence, often doesn't translate to reality in many disciplines. I'd personally like to see someone totally reinvent the concept of "theory"--create new models using IT, math, though some of that is already being attempted, but to totally reinvent the process...
Within a mere 2 days after quitting an SSRI (and I've done it about 6-8 times), I have a significant, noticable improvement in my mood/motivation/libido/cognition/enjoyment of activities, music, etc. A temporary hypomania at first...SSRIs do somehow supress my dopamine function.
But dopamine, though better than when on SSRIs, has yet to come back to my previous levels. Whether it translates to long term or not--I'd really like to know. It's sort of scary to think in terms of depending on articifial means to have dopamine in my brain - for the rest of my life.
Curious as to other reasons (aside from SSRIs) that people who've previously had adequate dopamine levels all their life would suddenly have dopamine mysteriously disappear from their brains. So--are there studies of people with sudden onset of LOW dopamine/dysfunction who have never taken SSRIs? That's where I would look first personally (if I had the mental devotion to look into it). Not that it is as simple as 'producing' low/high dopamine
Posted by garnet71 on April 9, 2009, at 9:22:54
In reply to Re: Dopamine depletion: A myth? » SLS, posted by garnet71 on April 9, 2009, at 9:19:00
But what incentive would one have to study such a thing?
If SSRI usage was to actually cause low dopamine, that would mean more drug usage after they are quit being taken = $.
(from behavioral economics - people/organizations only respond to incentives.)
Posted by garnet71 on April 9, 2009, at 9:33:12
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
Another thing I noticed - wouldn't the selection of the sample subjects (in general) normally taint studies to being with?
People are being paid to participate in a lot of studies, so wouldn't that siphon study subjects out of the population with certain common attributes?
I mean, even as a non-scientist, whenever I read about a study, there's always something that immeditately jumps out at me that I recognize could taint it. I can't not notice. Whether it really matters in the end, of course I don't know, but there are always noticable things...
Sorry to get off in a tangent, Scott...I wasn't even going to check this forum today. Ok, I'm done for now. lol
Posted by Relapse on April 9, 2009, at 11:01:12
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
Scott,
Ya know this is very non-scientific, but as Bush said I don't want to use the Googler. I was on ssri's for over 10 years and about a year ago, quit. I took an early retirement, so my stress level went way down. Man, when the meds cleared out of my system, I felt better than I had in years. On AD's I felt very emotionally boxed in. I told anyone who would listen, I would never take the drugs again. It was a pretty good run, it seemed like the rich emotion of life filled me again. Then I started having some symptoms and I told myself not to worry. I had the worst crash of my life in terms of intensity and duration. I should have know, since I have had many past events. I just thought without the stress and all.. I am doing better on the meds (including Zoloft) now. No mystery I feel emotionally boxed in again. Dopamine depletion? From a user standpoint, I would believe it. However, Zoloft is the drug that seems to get me a few rungs up the latter of mental health. Perhaps in the future, I can get my pdoc to look at some alternative meds to ssris. I have not tried any of the older drugs. I think like so many docs these days they are very reluctant to use them. Be well - Dave
Posted by myco on April 9, 2009, at 11:17:57
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
The evidence in studies ive looked at is contradictory for the most part. I do believe that AD use can reduce the firing rate of DA neurons - there seems to be enough consistant evidence to show this. So I agree with you that they moderate a change in neural activity.
> Yes, I have heard for years that SSRIs cause dopamine depletion, and that this might be responsible for the induction of apathy/amotivation/anhedonia or a loss of therapeutic effect ("poop-out"). However, where is there scientific evidence to support this notion? I would say that chronic SSRI usage might produce a change in the activity of neural pathways afferent to dopaminergic structures and circuits. However, to think that neurons actually run out of neurotransmitter seems unlikely to me. They probably are just not being stimulated to release the dopamine that they keep in storage.
>
> What do you think? Is there any scientific evidence that demonstrates that an SSRI can produce dopamine depletion downstream?
>
>
> - Scott
>
Posted by Phillipa on April 9, 2009, at 12:11:50
In reply to Re: Dopamine depletion: A myth? » SLS, posted by myco on April 9, 2009, at 11:17:57
If SSRI's and Snri's reve you up even on benzos what does that mean? Does it mean the hormones and thyroid have a higher impact on mental health than first thought? Phillipa
Posted by desolationrower on April 9, 2009, at 14:33:04
In reply to Re: Dopamine depletion: A myth?, posted by Phillipa on April 9, 2009, at 12:11:50
well, this seems like a theory thought up by people who think they can understand the brain (i don't mean, 'idiots', i mean, overconfident and not realizing the complexity). i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter. not that the idea of 'depletion' is completely crazy, theres some evidence that NA can be depleted in certain circumstances naturally, and i think mdma use depletes serotonin, but where does this theory come from? i haven't seen anything that says for instance that tyrosine hydroxylase is downregulated by ssris. if there is something going on it is probably a complex web keeping the equilibrium off like hypcortisolemia, downregulated 5ht2, or something like that. but looking at known effects of ssris seems like the place to start, not brotelligence about dopamine.
-d/r
Posted by bleauberry on April 9, 2009, at 16:11:00
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
I don't know if I could find it again, but one day surfing on pubmed I came across a study on rats where they showed that longterm ssri's caused the excess serotonin to be taken up by dopamine neurons. Theoretically an effort by genetic coding to deal with the artificially increased serotonin. If that is true, it would go a long way to explain poopout and ssri apathy syndrome. Serotonin getting involved in the dopamine circuits could do weird things like that, I imagine.
There must be some crosstalk between circuits. For example, Stahl wrote that Milnacipran will increase dopamine in the frontal cortex by blocking NE reuptake, because dopamine reuptake sites in the frontal cortex are lacking and the dopamine is normally taken up into the NE sites in that area.
I'm not sure about the dopamine depletion theory. I think serotonin taking a ride through the dopamine circuits where it doesn't belong makes more sense.
Posted by garnet71 on April 9, 2009, at 18:39:14
In reply to Re: Dopamine depletion: A myth?, posted by desolationrower on April 9, 2009, at 14:33:04
"i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter"
Hey crabby, er..genious, uh antibrotelligence..
not everyone can stay up all night AND read medical journals
and
not everyone can stay up all night OR read medical journals
Personally, I LIKE talking about "goofy" theories and "feeling" neurotransmitters that I can't even spell or pronounce. So - quit trying to ruin it for us all!
Posted by myco on April 9, 2009, at 18:47:38
In reply to Re: Dopamine depletion: A myth? » desolationrower, posted by garnet71 on April 9, 2009, at 18:39:14
ooo there you go again with the logic....youre just gettin me all ex-thhhited ova'ere
*tickles ya bum*
:oP
----------
> "i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter"
>
> Hey crabby, er..genious, uh antibrotelligence..
>
> not everyone can stay up all night AND read medical journals
>
> and
>
> not everyone can stay up all night OR read medical journals
>
> Personally, I LIKE talking about "goofy" theories and "feeling" neurotransmitters that I can't even spell or pronounce. So - quit trying to ruin it for us all!
Posted by Garnet71 on April 9, 2009, at 18:52:09
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by myco on April 9, 2009, at 18:47:38
Myco, seriously...
I WOULD KICK YOUR *SS
if you ever tried anything like that
Posted by myco on April 9, 2009, at 19:00:59
In reply to Re: Dopamine depletion: A myth? » myco, posted by Garnet71 on April 9, 2009, at 18:52:09
LOL ahhh.. trouble seeing through jokes huh hun. s'ok, we all have our days...you dont know me hun...dont judge :o)
> Myco, seriously...
>
> I WOULD KICK YOUR *SS
>
> if you ever tried anything like that
Posted by Garnet71 on April 9, 2009, at 20:09:25
In reply to Re: Dopamine depletion: A myth? » Garnet71, posted by myco on April 9, 2009, at 19:00:59
Myco, not judging...just my initial reaction. I'm not mad at you.
Don't worry about it...No hard feelings, ok?
:)
Posted by myco on April 9, 2009, at 20:50:30
In reply to Re: Dopamine depletion: A myth?, posted by Garnet71 on April 9, 2009, at 20:09:25
of course not... just know i'm not a bad guy ok.
*hugs
> Myco, not judging...just my initial reaction. I'm not mad at you.
>
> Don't worry about it...No hard feelings, ok?
>
> :)
Posted by Phillipa on April 9, 2009, at 21:25:35
In reply to Re: Dopamine depletion: A myth? » Garnet71, posted by myco on April 9, 2009, at 20:50:30
Myco well doesn't everyone know that already? Greatest person I know. Love Phillipa
Posted by yxibow on April 10, 2009, at 2:14:59
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
> Yes, I have heard for years that SSRIs cause dopamine depletion, and that this might be responsible for the induction of apathy/amotivation/anhedonia or a loss of therapeutic effect ("poop-out"). However, where is there scientific evidence to support this notion? I would say that chronic SSRI usage might produce a change in the activity of neural pathways afferent to dopaminergic structures and circuits. However, to think that neurons actually run out of neurotransmitter seems unlikely to me. They probably are just not being stimulated to release the dopamine that they keep in storage.
>
> What do you think? Is there any scientific evidence that demonstrates that an SSRI can produce dopamine depletion downstream?
>
>
> - Scott
>
I'm not sure about long term effects but I know, at least by evidence based psychiatry that a large dose of Luvox appeared to 'downregulate' dopamine. To this day with my orphan disorder the source of D2 accentuation is unknown, but before I started on Seroquel I did try a test with high dose Luvox. It helped a bit with the bright lights and the milieu of other symptoms.(See Luvox posting)
So if that's an example of depleting in the present sense, then I guess that fits in that picture.
There is one exception to current SSRIs -- Zoloft actually has a very minor action at D2, possibly blockading like an AP, but its unclear.
-- Jay
Posted by myco on April 10, 2009, at 13:25:44
In reply to Re: Dopamine depletion: A myth?, posted by desolationrower on April 9, 2009, at 14:33:04
I can feel the effect to some extent....when I tool tyrosine and "listened" closely to my body and feelings I could feel stages coming on...from head dizzyness, enlightenment, sleepyness, then energy and irritation....pretty much in order. I am on nardil but this was evident in terms of feel. So can you argue that this is the "feel of neuros"? I dunno...but knowing the theory of what these neuros are supposed to do to you...I can actually correlate that to some extent. Those that are on so many meds...I doubt can pick out what is doing what with any real confidence....but mabye my own experience is placcbo..who knows. But something is there...its not goofy at all. Just misunderstood....isnt that in the nature of modern understanding of the brain anyway?
m
------
> well, this seems like a theory thought up by people who think they can understand the brain (i don't mean, 'idiots', i mean, overconfident and not realizing the complexity). i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter.
Posted by garnet71 on April 11, 2009, at 10:21:20
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
Well here's another (non-technical) article I came across..I was looking at addiction stuff because I remember reading a similar article about low dopamine and addictions in the past that came from "addiction" studies.
http://floridadetox.com/graphics/images/AntidepressantsCanIncreaseDepressionDecreasingDopamine.pdf
Maybe there's more information in addiction research about this than we know, rather than in the neuro and pharma journals.
Posted by garnet71 on April 11, 2009, at 10:31:33
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
well here's some links to some full text research, though older, the links are embedded in text on the site. I don't know if its the right stuff you are looking for or if it would help answer your question, because i generally don't read this technical stuff or need a translator. (I have no clue)
http://www.nature.com/npp/journal/v20/n5/full/1395291a.html
Functional interactions between central serotonin (5-HT) and dopamine (DA) systems have been well documented. Electrophysiological, biochemical, and behavioral evidence suggests that the ascending serotonergic pathways from the medial and dorsal raphe modulate or control the function of the mesolimbic and mesostriatal dopamine systems (Joyce 1993; Zazpe et al. 1994; Kapur and Remington 1996). The modulating effect of serotonin on striatal dopamine release is, however, controversial. For example, there is evidence that serotonin may inhibit (de Belleroche and Bradford 1980; Ennis et al. 1981; Westfall and Tittermary 1982; Blandina et al. 1988) as well as stimulate DA release in the striatum (Benloucif et al. 1993; West and Galloway 1996; De Deurwaerdere et al. 1997). Similarly, local application of 5-HT or 5-HT agonists have been shown to reduce (de Belleroche and Gardiner 1982) and facilitate dopamine efflux in the nucleus accumbens (Guan and McBride 1989; Parson and Justice 1993). In respect to the 5-HT2 receptor agonist properties of psilocybin, it is of particular note that 3,4-methylenedioxymethamphetamine (MDMA), a potent 5-HT releasing agent, has been shown to increase impulse-mediated striatal dopamine release through 5-HT2 receptor activation (Schmidt et al. 1992; Palfreyman et al. 1993; Schmidt et al. 1994; Yamamoto et al. 1995; Gudelsky and Nash 1996). Thus, 5-HT2A receptors located on dopaminergic and/or GABAergic neurons within the striatum and nucleus accumbens might provide an anatomical substrate for a serotonin-mediated psilocybin-induced dopamine release (Palacios et al. 1991).
Posted by garnet71 on April 11, 2009, at 10:42:23
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
okay, one more.
http://www.mcmanweb.com/dopamine.html
it's more aggregate and contextual (my kind of article)
I'm still interested in this topic, let me know what you guys think
Posted by myco on April 11, 2009, at 11:33:47
In reply to Re: Dopamine depletion: A myth? » SLS, posted by garnet71 on April 11, 2009, at 10:21:20
I totally agree with you garnet...addiction research should play an integral role along side the biochem/physiol/psychopharm research. More angles reduce bias in thinking.
:o)
> Well here's another (non-technical) article I came across..I was looking at addiction stuff because I remember reading a similar article about low dopamine and addictions in the past that came from "addiction" studies.
>
> http://floridadetox.com/graphics/images/AntidepressantsCanIncreaseDepressionDecreasingDopamine.pdf
>
> Maybe there's more information in addiction research about this than we know, rather than in the neuro and pharma journals.
Posted by linkadge on April 12, 2009, at 7:24:27
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by myco on April 11, 2009, at 11:33:47
The documentation of SSRI induced apathy is fairy comprehesnive. SSRIs are associated with increased likelyhood of developing parkinsons and sympom worsening in parkinsons disease. In animal models the SSRI's have also been linked to neuroanatomical changes to brain structures involved in movement.
Linkadge
Posted by linkadge on April 12, 2009, at 7:26:27
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by myco on April 11, 2009, at 11:33:47
Some suggest the accumulation of serotonin in dopaminergic nerve terminals is part of the theraputic effect. Some suggest that it is detrimental to the theraputic effect.
Linkadge
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