Low Dose SSRI (Reinstatement)

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pete
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Low Dose SSRI (Reinstatement)

Unread post by pete »

Some experiment i want to share.
First i tried to go back on paxil - bad idea. That ended in serotonin syndrome very fast. (5mg for 10 days)
But i noticed that if i take such a single low dose of 2.5mg i will get enormous improvements of sexual function in the next 2 days.
Everything above that dose or even 2 days in a row made things worse.
So i decided to take 2.5mg just 2-3 times a week for some time. Later i switched to 1-2 times.
Here is what happened.

week 1:
weird little zaps all over the body (even in the eye, wtf) like fast changing feeling of hot and cold (hard to describe)
spantanous hard rock erection all day
higher libido

week 2:
feeling of hormonal change: whole muscles are deeply relaxed, but feeling aggressive.
sexual improvements subsiding
intensive dreaming

week 3:
feeling like chewing gum
first giant emotional, tsunami like wave hit me: i was crying for hours, learned again how enjoyable music can be, what horripilation is, that my pssd state is much more fucked than i thought, ....
next day another huge wave. the other day also and so on.
sexual function almost normal

week4:
things are fading away.
to do not more damage, i decided to stop. no more intake since then

week5:
pssd again

week6:
like week 3, but more stable

week7:
almost normal

week8:
getting slowly worse

week9:
pssd again, but baseline is still improved

I got the feeling it's all about these little zaps. what is this? acetylcholine? ion channels?
Maybe its like this: ion channel dysregulation -> hormanal imbalance -> 5-ht1a downregulation? just a thougth.

Just in case someone wants to try this, keep in mind paxil got lower halftime than most ssri.

Of course it sucks that it flipped back but also I'm pretty optimstic now, I don't believe there is much damage in my case. I think there is just something stucked in disadventegous homoestasis.

I will do another trail in the near future with just 1x per week over longer period.
Last edited by pete on Mon Aug 29, 2016 4:51 am, edited 1 time in total.
ssinus
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Re: low dose ssri

Unread post by ssinus »

Hello Pete, thanks for your update.
Could you describe in more details what it does with genital anesthesia/numbness - any improvement there ?
what about semen amount - fuller, watery ? more flaccid hang or ?

I'm thinking about the same, just to try the small dosage for 2-3 days. My first experiment with SSRI was with Sertraline for maybe 5 days no libido issues. Then I tried Paxil for 11 days and this fucked me up completely.
I took it for PE not depression. Now I have full blown PSSD.
But I think I would try either fluvoxamine (which as per few reports cured PSSD symptoms completely- not sure for how long though:/, and not sure if it is true) or sertraline which acts also on dopamine.
I believe this 5ht1a desensitization theory - it seems the problem is not 5ht1a down regulation but desensitization caused by uncoupling with G proteins since after acute ssri treatment as per the studies 5ht1a concentration was the same as prior the treatment but lacking G protein coupling. If statements that ssri reinstatement helped some people to cure PSSD are true then it has to be just some switch to be turned on by correct SSRI dosage (but acute treatment just for few days) - but at the end this is just my thought.
pete
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Re: low dose ssri

Unread post by pete »

Hi ssinus,
Sure, it improves all symptoms.
Numbness was gone and semen amount was more and less transparent.
ssinus wrote: I believe this 5ht1a desensitization theory - it seems the problem is not 5ht1a down regulation but desensitization caused by uncoupling with G proteins since after acute ssri treatment as per the studies 5ht1a concentration was the same as prior the treatment but lacking G protein coupling.
I don't see how another ssri intake could undo this.
fasttrack1982
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Re: low dose ssri

Unread post by fasttrack1982 »

I agree that in the short run, an SSRI could improve PSSD symptoms. Similar to the fact that antipsycotics which cause Tardive Dykinesia will also in some cases alleviate symptoms when taken in the short run. It is consistent with the idea that somehow the brain has become desensitived to serotonin, and that in the beggining adding more serotonin via SSRI will add benefit by activating more receptors, prior to it potentially causing further damage. It is tempting to try it.
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Ghost
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Re: low dose ssri

Unread post by Ghost »

pete wrote:Hi ssinus,
Sure, it improves all symptoms.
Numbness was gone and semen amount was more and less transparent.
ssinus wrote: I believe this 5ht1a desensitization theory - it seems the problem is not 5ht1a down regulation but desensitization caused by uncoupling with G proteins since after acute ssri treatment as per the studies 5ht1a concentration was the same as prior the treatment but lacking G protein coupling.
I don't see how another ssri intake could undo this.
It is G proteins. It's downstream of the 5HT1A receptor. Once I realized this, my entire view of PSSD changed. I think it's Go and Gi2, which are decreased 3 days after the start of SSRI. The problem isn't at the receptor binding site, it's between the receptor and the GIRK Channel. This is huge, because it greatly narrows the search. It's like taking a magnifying glass, and getting closer to the cause.

Also close to the cause: Cortisol. I think we have a positive reinforcement of the system. Postsynaptic 5HT binding releases cortisol. So if you have PSSD, you inherently have higher cortisol. Interestingly...Cortisol decreases 5HT1A autroreceptor ability to hyperpolarize the presynaptic membrane. So, could cortisol be the key to keeping us stuck in PSSD? It's possible that it is a large part.

Read:

http://www.ncbi.nlm.nih.gov/pubmed/8930214

and

Chronic fluoxetine induces opposite changes in G protein coupling
at pre and postsynaptic 5-HT1A receptors in rat brain:

M. Elena Castro, Alvaro Diaz, Elena del Olmo, Angel Pazos

http://www.academia.edu/6453502/Chronic ... _rat_brain
- Medical Student & Friendly poltergeist - Lexapro Sept '14. [Hx] [PSSD Lab] [r/PSSD] [Treatment Plan] - Add "Ghost" in replies so I see it :)
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Ghost
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Re: low dose ssri

Unread post by Ghost »

Even after a few weeks of SSRI, Cortisol levels were STILL doubled. We're closing in on PSSD cause I think. I'm hoping beyond hope that Cortisol is a large player, because it could be blocked, causing 5HT1A AR to resensitize, and normalizing the 5HT function pre-ssri. If it is Cortisol induced, then we'd be able to snap the positive feepback loop. Stress also decreases receptor activity due to adenyl cyclase uncoupling.
- Medical Student & Friendly poltergeist - Lexapro Sept '14. [Hx] [PSSD Lab] [r/PSSD] [Treatment Plan] - Add "Ghost" in replies so I see it :)
ssinus
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Re: low dose ssri

Unread post by ssinus »

I agree with this - right after I got PSSD I went to endocrinologist to check my hormone levels, he mentioned I have elevated cortisol but still in the normal range cause by stress. Also the worst part of the PSSD day is morning, when I wake up I have pretty good flaccid hang but within a couple of minutes I feel how anesthesia becomes worse - shrinkage etc. As far as I know the cortisol is highly elevated in the morning right after you wake up.
I discussed this cortisol thing on my 3rd different endocrinologist visit and she said that Im in range and if cortisol would be a problem I would have either cushing syndrome (elevated cortisol) or adrenal fatigue and neither of the is the cause of my problem. But the "normal" range is bullshit, everyone is different so any offset may cause some cascade reaction. I have tried to lower it by just using some vitamins, maybe it would be worth it to try some stronger player.

Do you have any study to share with us saying that by lowering cortisol you enable 5ht1a auto-receptors to re-sensitize ?
pete
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Re: low dose ssri

Unread post by pete »

Thanks Ghost. What do you think about low dosing ssri as possible cure? Does it make any sense?
DoIt
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Re: low dose ssri

Unread post by DoIt »

I think too that Cortisol plays a huge role. My PSSD got a lot worse after big stress last Spring... And I also notice worse symptoms in the morning and during the mid-afternoon and it gets better in the evening :/

But I feel ok for the first half hour after waking up...
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Ghost
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Re: low dose ssri

Unread post by Ghost »

ssinus wrote:I agree with this - right after I got PSSD I went to endocrinologist to check my hormone levels, he mentioned I have elevated cortisol but still in the normal range cause by stress. Also the worst part of the PSSD day is morning, when I wake up I have pretty good flaccid hang but within a couple of minutes I feel how anesthesia becomes worse - shrinkage etc. As far as I know the cortisol is highly elevated in the morning right after you wake up.
I discussed this cortisol thing on my 3rd different endocrinologist visit and she said that Im in range and if cortisol would be a problem I would have either cushing syndrome (elevated cortisol) or adrenal fatigue and neither of the is the cause of my problem. But the "normal" range is bullshit, everyone is different so any offset may cause some cascade reaction. I have tried to lower it by just using some vitamins, maybe it would be worth it to try some stronger player.

Do you have any study to share with us saying that by lowering cortisol you enable 5ht1a auto-receptors to re-sensitize ?
I'll look for the quote (Sadly it's in my physical PSSD-research records (which I don't have on me now) and not on my computer drive pdf stash- I'd try to google it maybe?). I'll attach the graphic that shows elevated cortisol release in hypothalamus as a result of Prozac. Note how it remains elevated

Stress-induced 5-HT,, receptor desensitization:
protective effects of Ginkgo biloba extract (EGb 761
): (Bolainos-Jimenez, 1996)

This study shows it's partially from stress (although I think that this is adenylyl cyclase mediated) :

Abstract:

Summary - The effects of sub-chronic cold stress on the functioning of hippocampal 5-HT,, receptors in old isolated rats and the
possible protective effects of Ginkgo biloba extract (EGb 761) were investigated. Cold exposure during five days, produced a
significant reduction of the inhibitory effect of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) on forskolin-stimulated
adenylyl cyclase activity. In contrast, neither the affinity nor the density of hippocampal [3Hl8-OH-DPAT binding sites were affected
indicating that the reduced sensitivity of 5-HTl, receptors induced by stress is probably due to a modification of their coupling
mechanisms to adenylyl cyclase. The stress-induced desensitization of 5-HTl, receptors was prevented by the administration of EGb
761 (50 mglkg per os/14 days). These results clearly indicate that 5-HTI, receptors are desensitized by stress and point out the
reduced capacity of old rats to cope with the adverse effects of a chronic stressor. EGb 761 appears to restore the age-related
decreased capacity to adapt to a chronic stressor.

This is from the study I posted last night:

"Our data demonstrate that fluoxetine-induced desensitization of 5-HT1A autoreceptors
occurs at G protein level."

Pete, There is something stuck in a positive feedback loop, and I'm still working on my theory of exactly what that is. I think I'll have a good answer to the question in a few weeks though.
- Medical Student & Friendly poltergeist - Lexapro Sept '14. [Hx] [PSSD Lab] [r/PSSD] [Treatment Plan] - Add "Ghost" in replies so I see it :)
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