Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

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anacleta
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Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by anacleta »

Melcangi phase one study! for now the abstract

Highlights
•Brain neuroactive steroid levels are altered by paroxetine treatment.

•Brain neuroactive steroid levels are altered after one-month withdrawal.

•Paroxetine treatment and withdrawal did not affect steroid plasma levels.

•Brain expression of steroidogenic enzymes is affected by paroxetine treatment.

•Brain expression of steroidogenic enzymes is affected after one-month withdrawal.


Abstract
Selective serotonin reuptake inhibitors (SSRI) show high efficacy in treating depression, however during treatment side effects, like for instance sexual dysfunction, may appear, decreasing compliance. In some cases, this condition will last after drug discontinuation, leading to the so-called post-SSRI sexual dysfunction (PSSD). The etiology of PSSD is still unknown, however a role for neuroactive steroids may be hypothesized. Indeed, these molecules are key physiological regulators of the nervous system, and their alteration has been associated with several neuropathological conditions, including depression. Additionally, neuroactive steroids are also involved in the control of sexual function. Interestingly, sexual dysfunction induced by SSRI treatment has been also observed in animal models. On this basis, we have here evaluated whether a subchronic treatment with paroxetine for two weeks and/or its withdrawal (i.e., a month) may affect the levels of neuroactive steroids in brain areas (i.e., hippocampus, hypothalamus, and cerebral cortex) and/or in plasma and cerebrospinal fluid of male rats. Data obtained indicate that the SSRI treatment alters neuroactive steroid levels and the expression of key enzymes of the steroidogenesis in a brain tissue- and time-dependent manner. Indeed, these observations with the finding that plasma levels of neuroactive steroids are not affected suggest that the effect of paroxetine treatment is directly on neurosteroidogenesis. In particular, a negative impact on the expression of steroidogenic enzymes was observed at the withdrawal. Therefore, it is possible to hypothesize that altered neurosteroidogenesis may also occur in PSSD and consequently it may represent a possible pharmacological target for this disorder.


https://www.sciencedirect.com/science/a ... 3021002389
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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 was proven countless times that hormones are mostly normal in people with PSSD. This study proves to me one thing - that those who do the research on PSSD have no fucking idea how to bite it. I hope this study was not crowdfounded, because otherwise it was daylight robbery.
There are many theories on why PSSD occur, some more likely than the others, but all of them involve serotonin and have to involve serotonin as a major factor.
arahant
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by arahant »

guacamo wrote: Fri Jul 23, 2021 8:09 am It was proven countless times that hormones are mostly normal in people with PSSD. This study proves to me one thing - that those who do the research on PSSD have no fucking idea how to bite it. I hope this study was not crowdfounded, because otherwise it was daylight robbery.
There are many theories on why PSSD occur, some more likely than the others, but all of them involve serotonin and have to involve serotonin as a major factor.
If you stop being judgmental and arrogant regarding crowdfunding, basing yourself on forum brocience that led to nowhere, and care to read the whole study published at the peer-reviewed journal Psychoneuroendocrinology by scientists, you will realize that was found no statistical difference in PLASMA levels as you pointed and everyone knows, but that was not what happened on neurostetoids levels on the brain both on subchronic drug intake and after one-month withdrawal.
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guacamo
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by guacamo »

You can modify your hormone levels by taking exogenous hormones, protip it will do jack shit. It is no bro science, you can form your opinion based on my research and give this idea a like or not, if this idea will fail i will try to go another path , but i do not take money from anyone to go and spend it on whatever came to my mind.
All it proves to me is they do not know from where to start and how to start, they can do thousand papers about what SSRIs change in the brain because they change a ton of things, if they do it in such a manner, not a single one will touch the real subject.
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by Frog »

guacamo wrote: Fri Jul 23, 2021 4:37 pm You can modify your hormone levels by taking exogenous hormones, protip it will do jack shit. It is no bro science, you can form your opinion based on my research and give this idea a like or not, if this idea will fail i will try to go another path , but i do not take money from anyone to go and spend it on whatever came to my mind.
All it proves to me is they do not know from where to start and how to start, they can do thousand papers about what SSRIs change in the brain because they change a ton of things, if they do it in such a manner, not a single one will touch the real subject.
For me the important thing is that this research, by a high profile individual, will raise more awareness and bring credibility to the condition. It could also prove whether or not neurosteroids are involved. Either way it’s good news as it gives us a better idea of where to look next. One of my old teachers used to say to me that pseudoscience seeks to prove a hypothesis correct where as science seeks to prove it wrong. The absence of evidence is in itself evidence.
arahant
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by arahant »

guacamo wrote: Fri Jul 23, 2021 4:37 pm You can modify your hormone levels by taking exogenous hormones, protip it will do jack shit. It is no bro science, you can form your opinion based on my research and give this idea a like or not, if this idea will fail i will try to go another path , but i do not take money from anyone to go and spend it on whatever came to my mind.
All it proves to me is they do not know from where to start and how to start, they can do thousand papers about what SSRIs change in the brain because they change a ton of things, if they do it in such a manner, not a single one will touch the real subject.
what's your research? other collecting a bunch of PubMed papers and look for anecdotes in forums that confirm it.
"if this idea will fail i will try to go another path"
That's exactly the confirmation bias that populates every pseudoscience around, looking only for evidence that confirms it.

As Frog mentioned to his professor above, science starts with a negative hypothesis.

Melcangi's research started with a default/null hypothesis of no difference in neurosteroids on the brain and plasma and it was measured in a controlled experiment.
And it was not a "fail" as you mentioned, because they could not reject the hypothesis that differences in the brain (not in plasma levels) between both subchronic intake and one month after withdrawal, were statistically significant.

It looks like you are not aware of how basic bioscience works and its hierarchy. It always starts with preclinical in vitro/Vivo studies, for the simple reason that is easier to measure in animal models first than in humans.
Trying to verify hypotheses and move next to safer experiments designed to reach human trials, in small steps.
Every new treatment needs thousands of papers to reach the public.
Wellbutrin (2007 - 2018)
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Wellbutrin + Ritalin (2016 - 2018)
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guacamo
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by guacamo »

My point stand still, there are thousands better studies to start from, the sad part is there will never be enough funding to do a thousand studies to come to a point, so every cent has to be the money well spend. Still one study is better than no one. Perhaps you are right and im overly pessimistic, i am sorry for that. If you want to discuss with me philosophy of science i am open to this, a lot of theories started from the confirmation bias in one way or another.
It's about having an idea and throwing it at the wall of reality and observing if it crumbles or not. Hell, even development of the SSRIs was born in somewhat that way.
The idea "that pseudoscience seeks to prove a hypothesis correct where as science seeks to prove it wrong" is overly simplistic to me, sometimes science is doing both at the same time, other time does the former, another the latter.
Last edited by guacamo on Sat Jul 24, 2021 10:17 am, edited 8 times in total.
ryjoseph97
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by ryjoseph97 »

I just saw my doctor and told him I think I have PSSD. I also told him about this study and he asked me to send it to him. He said most of the literature he is aware of supports the notion that sexual disfunction from ssris is reversible. But he said he will look into it further, which is encouraging to me.

I think the recency of this study helps a lot - it lets doctors know that the jury is still out on PSSD. I think it is important to share this study with doctors when trying to explain our condition.
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Re: Melcangi, EFFECTS OF PAROXETINE TREATMENT AND ITS WITHDRAWAL ON NEUROSTEROIDOGENESIS

Unread post by ryjoseph97 »

Does the lack of change in plasma levels suggest that traditional blood work won't reveal any changes in neurosteroid levels?
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