Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

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Jaxx
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by Jaxx »

Great to see another publication about PSSD. However, i do understand the point made that research on the effects of SSRI's is not exactly the same as finding markers for PSSD in humans and we understand what PSSD is and why it happens.
Let's hope it will evolve to this type of research one day.
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guacamo
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by guacamo »

ryjoseph97 wrote: Sat Jul 24, 2021 9:29 am Does the lack of change in plasma levels suggest that traditional blood work won't reveal any changes in neurosteroid levels?
Very likely yes, but neurosteroids role in PSSD is most likely neglible or atleast does not play a major way, look at the fact that it induced post-treatment changes in rats and if you extrapolate this study to humans, then everyone who ever took SSRIs would develop PSSD, which is obviously not true, it is very simple logic, that's why i am a bit pessimistic on this study. There are many studies done on SSRIs that found long term changes in the brain and these did not cause PSSD, this study is nothing new. Future studies should consider what treatment cured PSSD in some and then try to interconnect familiar mechanism between them and from that point try to organize new research. It should be rather obvious that future focus has to be put on serotonergic system, because serotonergic substances almost always affect PSSD by either inducing windows or crash, it is not a rocket science. SSRIs, Inositol, ashwagandha, st john wort, mirtazapine, trazodone, lithium, mushrooms, cannabis, they all do affect IP3 receptor on ER, there is also 5-HT1A, which most of these supplements in some way act on this receptor, these are promising topics for future research. If there would be a procedure that could make rodents develop PSSD, it also would make things way simpler.
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by Meso »

guacamo wrote: Sat Jul 24, 2021 3:43 pm Very likely yes, but neurosteroids role in PSSD is most likely neglible or atleast does not play a major way, look at the fact that it induced post-treatment changes in rats and if you extrapolate this study to humans, then everyone who ever took SSRIs would develop PSSD, which is obviously not true, it is very simple logic, that's why i am a bit pessimistic on this study. There are many studies done on SSRIs that found long term changes in the brain and these did not cause PSSD, this study is nothing new. Future studies should consider what treatment cured PSSD in some and then try to interconnect familiar mechanism between them and from that point try to organize new research. It should be rather obvious that future focus has to be put on serotonergic system, because serotonergic substances almost always affect PSSD by either inducing windows or crash, it is not a rocket science. SSRIs, Inositol, ashwagandha, st john wort, mirtazapine, trazodone, lithium, mushrooms, cannabis, they all do affect IP3 receptor on ER, there is also 5-HT1A, which most of these supplements in some way act on this receptor, these are promising topics for future research. If there would be a procedure that could make rodents develop PSSD, it also would make things way simpler.
I agree with you. I've always voiced my concern over this study and how it doesn't cover other SSRIs that don't interact with neurosteroids yet still trigger PSSD. It's looking at a single aspect that might be involved in some cases only while ignoring other important ones.

However, like Jaxx has said, it's great to see another publication about PSSD so let's hope it will evolve to more promising types of research one day. There's no need to be harsh with criticism.
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anacleta
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by anacleta »

a colleague from Melcangi gave me this link to the full text, which can be shared and is valid until 14 September 2021
https://authors.elsevier.com/c/1dTfu15hUdTGgL
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guacamo
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by guacamo »

It's impressive, despite my initial disdain I must say it was well orchestrated study done by competent individual. I am looking forward for his research, hopefully next will be on serotonergic system or g protein signal transduction in regard of PSSD.
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by arahant »

guacamo wrote: Fri Jul 30, 2021 11:30 am It's impressive, despite my initial disdain I must say it was well orchestrated study done by competent individual. I am looking forward for his research, hopefully next will be on serotonergic system or g protein signal transduction in regard of PSSD.
That's why I recommended you read the whole study before any disdain. The study was conducted with scientific rigor, that's also why It got published in a journal.
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anacleta
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by anacleta »

Observations on the study (as an ignoramus on neurosteroids)

The sample of rats examined does not have PSSD.
If PSSD is an exception among people, it probably is among rats (assuming the rats get PSSD). No behavioural observation study was conducted on the rats before sacrificing them all. So we do not know whether they lost their sexual behaviour following paroxetine.

The persistent neurosteroid alterations are there.
Are they fairly homogeneous in all the rats, or are they very unevenly distributed? Is the response of rats very subjective as among people? What these alterations cause? Any symptoms? Perhaps ascribable to withdrawal syndromes? not known for now. Research needs to go further and further into detail.

However, I think it would be really interesting, and perhaps not so expensive, an experimental study with observation of animal behaviour, with the aim of finding, if there is one, an animal model of PSSD.

Select 40 healthy male rats and observe their sexual behaviour in a controlled environment, take note. Then administer an SSRI to 20 of these rats, in equal doses, for X days. Then stop the treatment and allow 30 days to pass treating rats equally. Now recreate the controlled context to observe the sexual behaviour of ALL the rats. You will see if the 20 SSRI-treated rats, or even just 1 or a few of them, have drastically reduced their sexual behaviour.
You will be able to compare the level of sexual behaviour of the previously SSRI-treated group to the untreated group. And the unfortunate rats that will not have recovered their sexual behaviour at all, they will be a valuable animal model of PSSD on which to look for alterations in neurosteroids, small fibres, receptors, alterations in gene expression...as well as on which to test treatments.
Last edited by anacleta on Mon Sep 06, 2021 11:22 am, edited 1 time in total.
Thomas
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by Thomas »

As an ignoramus on neurosteroids ((c) anacleta ;)), am I missing something? I find this really interesting...
1) Hormonal imbalance is the first explanation any doctor will think of for our symptoms but was discarded because plasma levels are usually normal.
2) This theory (is it a theory? I am not sure, though, as they don't explain underlying causes) seems consistent with lots of things, especially us failing while trying to fix serotonin/dopamin/whatever signalling
Escitalopram, 10mg/day, Jan-May 2019. Fluoxetine, May-Sept 2019. Mirtazapine 7,5mg/day, November 2019-January 2020. Escitalopram, 5mg/day, Feb-May 2020.
Symptoms: sexual & emotional numbness
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