FDA Approves Allopregnanolone As A Fast-acting, Long-lasting Antidepressant

haidut

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As many of forum users know, one of the real mechanisms of action of the SSRI drugs is not the increased serotonin but the increase in brain allopregnanolone these drugs cause. As such, there has been (secret) interest from Big Pharma for years in both allpregnanolone and its synthetic derivatives as antidepressant drugs. I posted not long ago on the fact that FDA was looking at approving allopregnanolone as antidepressant.
Allopregnanolone May Soon Be Approved As A Fast-acting Antidepressant

Well, now it appears that FDA has made up its mind and has approved allopregnanolone (Brexanolone) as a fast-acting antidepressant for post-partum depression. The fact that works so rapidly (within 24 hours) makes it that much more attractive as depression treatment, especially in suicidal cases. Even more stunningly, the relief from depression lasted at least 30 days after the single infusion of the steroid. This synthetic steroid now has the potential to dwarf the sales of SSRI drugs that are falling (slowly) our of favor, take up to 4 weeks to produce effects, actually increase risk of suicide, and do not work on 40%-60% of the patients taking them.
While the approval is specifically for post-partum depression, this allows any doctor to prescribe it semi-off-label for depression due to any cause. This is both good and bad news. The good news is that pharma companies and FDA are finally starting to change science in a positive direction. The bad news is that now allopregnanolone is a prescription drug and its precursors like 5a-DHP, progesterone and even pregnenolone may become target for FDA to withdraw from market as effective precursors to the now-prescription drug allopregnanolone. All 3 have been shown to reliably increase allopregnanolone levels in the brain and the last two have decent evidence from human studies too.

https://www.nbcnews.com/health/womens-health/fda-approves-first-drug-postpartum-depression-n984521
"...But on Tuesday, the Food and Drug Administration approved the first drug specifically developed for postpartum depression, called brexanolone, or Zulresso. Brexanolone is novel because it has a synthetic form of the hormone allopregnanolone, a progesterone derivative, in it. The hormone increases throughout a woman’s pregnancy and then plummets after she gives birth, a possible contributor to postpartum depression."

"...In double-blind, placebo-controlled trials, many women with moderate to severe postpartum depression saw a marked improvement of their symptoms within just 24 hours of receiving the drug. That improvement was still present 30 days after the infusion, the length of the trial. “This is for postpartum depression, but it is a step in understanding how we treat depression more broadly,” said Dr. Samantha Meltzer-Brody, director of the perinatal psychiatry program at the University of North Carolina at Chapel Hill and the academic principal investigator in the brexanolone trials. “We have had the same treatments for depression for 30 years. There’s an enormous need for new, novel ways to treat depression, and to treat it quickly.”
 

johnwester130

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Isn't taking it directly incredibly dangerous ?

Peat wrote that prozac increases allopregnenolone too.
 

Cameron

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Would pregnenolone still be a safer way to increase allopregnenolone since it's more up stream of a steroid ? What about allopregnenolone supplementation and suppresion of natural allopregnenolone
 

ken

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I don't know if pregnenalone is safer, but certainly cheaper and more convenient. 34000 per treatment, sixty hours on an Iv for the new treatment. And I think only a five point improvement over a placebo. Maybe the placebo was sugar and saline.
 
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Kartoffel

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Isn't taking it directly incredibly dangerous ?

Peat wrote that prozac increases allopregnenolone too.

Several dangerous anti-depresants increase allopregnenolone as a "side effect". That's why they they sometimes work for a short period of time before the negative long-term effects set in.

I don't know if pregnenalone is safer, but certainly cheaper and more convenient. 34000 per treatment, sixty hours on an Iv for the new treatment. And I think only a five point improvement over a placebo. Maybe the placebo was sugar and saline.

Wow, just saw that. Think about how many bags of pregnenolone powder you could buy for that. I hope people read the studies showing that simply taking pregnenolone will make their allop. go up by several times before they spend their life savings on infusions.
 

Mauritio

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Would pregnenolone still be a safer way to increase allopregnenolone since it's more up stream of a steroid ? What about allopregnenolone supplementation and suppresion of natural allopregnenolone
I think he spoke against direct allopregnenolone supplementation in the 5adhp thread . It had something to do with allopreg's conversion into other metabolites and also a legality issue.
5adhp seems to be a quite safe way to raise allopregnenolone.
 

Jonas Miles

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Long-time lurker, first time poster. I have read some of these threads and have tried haidut's dhp product. I think that I have post-finasteride which is part of where my interest comes from, and I've certainly seen some speculation on whether Brexanolone as allopreg could help people with PFS.

A question I have now is related to the off-label prescribing issue. I understand that physicians can prescribe for just about any reason, so while even though this drug was approved for post-partum depression it's theoretically possible for a doctor to prescribe for PFS or anything else. But does that impact the likelihood that insurance would cover it, or is there actually a chance that a man could get insurance to cover Brexanolone for PFS when it's only approved for post-partum depression in women?

Kind of a crazy situation for a PFS-sufferer when it seems like whether Brex would actually help is totally speculative.
 

bk_

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I think he spoke against direct allopregnenolone supplementation in the 5adhp thread . It had something to do with allopreg's conversion into other metabolites and also a legality issue.
5adhp seems to be a quite safe way to raise allopregnenolone.

By “he” you mean Ray Peat? Do you have a quote on what he said about allopreg or 5aDHP?
 

Sativa

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Easy OTC ways for increasing natural production of Allopregnanolone: Agmatine & Palmitoylethanolamide
(They have countless other biological properties, which are complementary to longevity an quality of life etc)
Agmatine stimulates the endogenous synthesis of allopregnanolone via activation of the PPAR-α receptor & PGC1α (paper attached)
Palmitoylethanolamide is also a potent PPAR-α activator.
Palmitoylethanolamide (PEA) is synthesized from the same class of membrane phospholipids, the N-acylphosphatidylethanolamines, that are precursors for Anandamide. PEA is primarily catabolized by NAAA enzyme but is also a substrate for FAAH. PEA is an agonist at the peroxisome proliferator-activated receptor α (PPARα) but has no activity at the CB1R.

Palmitoylethanolamide is actually (normally) co-released alongside other endogenous cannabinoids, but sometimes this can malfunction. Palmitoylethanolamide is potent at reducing mast cell/histamine & general allergy related dynamics:
Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization,
PEA reportedly inhibits the release of pro-inflammatory mediators from activated mast cells [23,24] and reduces the recruitment and activation of mast cells at sites of nerve injury, events associated with anti-allodynic and anti-hyperalgesic effects in a model of neuropathic pain
 
J

jb116

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I'm always torn by these acknowledgments of good substances by the system. On one hand, its shows some sliver of rational thought and the right direction. On the other, the more and more good things are in the limelight, the more chance we lose access to them through their control of said substance or even its banning or some corrupted form. I'm always torn.
 

Sativa

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lol, i guess either exploit the ''system" as it presents itself, or indulge the theme of disempowered victim...BUT anyway, from an empowered perspective, agmatine is just the decarboxylated form of common OTC amino acid Arginine. PEA is OTC available world-wide. There's countless other PPAR-alpha activators, ofc.
 
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J

jb116

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lol, i guess either exploit the ''system" as it presents itself, or indulge the theme of disempowered victim...BUT anyway, from an empowered perspective, agmatine is just the decarboxylates form of common OTC amino acid Arginine. PEA is OTC available world-wide. There's countless other PPAR-alpha activators, ofc.
On paper that's well and good, but that also assumes the perpetrator is ignorant enough to be exploited. They aren't.
 

Sativa

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No idea what you mean.
Anyway, plenty of options & choices for those who look.
 
J

jb116

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I know, that's part of the issue. Options can be taken away or manipulated.
 

Sativa

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I know, that's part of the issue. Options can be taken away or manipulated.
Perhaps. Such thinking style is foreign to me since nothing actually happens 'to' me, as this would be quite a disempowering mentality for me to choose.
 
J

jb116

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Perhaps. Such thinking style is foreign to me since nothing actually happens 'to' me, as this would be quite a disempowering mentality for me to choose.
That is contingent on your values. If one values the truth then one can certainly reflect on the quality of that truth IE empowering or disempowering, but ultimately go on to excavate this truth and find Solutions to better one's life. I think often people mistake beneficial or empowering for "truth."
 

Blossom

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Easy OTC ways for increasing natural production of Allopregnanolone: Agmatine & Palmitoylethanolamide
(They have countless other biological properties, which are complementary to longevity an quality of life etc)

Palmitoylethanolamide is also a potent PPAR-α activator.
Palmitoylethanolamide (PEA) is synthesized from the same class of membrane phospholipids, the N-acylphosphatidylethanolamines, that are precursors for Anandamide. PEA is primarily catabolized by NAAA enzyme but is also a substrate for FAAH. PEA is an agonist at the peroxisome proliferator-activated receptor α (PPARα) but has no activity at the CB1R.

Palmitoylethanolamide is actually (normally) co-released alongside other endogenous cannabinoids, but sometimes this can malfunction. Palmitoylethanolamide is potent at reducing mast cell/histamine & general allergy related dynamics:
There was a similar thread from 2018 with some good discussion. I bought PEA at that time because my mom was ill on hospice and I was experiencing some issues related to the stress of that experience. I tried it again today thanks to your post serving as a reminder! It helped me finally get some nice restorative sleep that had been alluding me since going back to night shift work.
Allopregnanolone May Soon Be Approved As A Fast-acting Antidepressant
 
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