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Rapid onset of PSSD suggests 5ht1a theory wrong??

Unread postPosted: Sat Nov 24, 2018 11:30 am
by Emu
More of a question/observation than a hypothesis and I'll provide a much fuller account of my experiences below in case anyone's interested, but essentially my point is this: if 5ht1a receptor downregulation, a process which is believed to take several weeks, is both the principle mediator of the effects of SSRIs as well as the most likely trigger for PSSD, how come my sexual dysfunction started almost immediately on taking Citalopram? Following reports on here moreover that some people had benefited from SJW, a drug which is also believed to function like an SSRI, on trying it at a low dose for a few days a couple of months ago, the modest improvements I'd gradually been accumulating in the 15 months since stopping Citalopram were pretty much extinguished in 2-3 days!

Other than a suspicion that the amygdala may in fact play a part in the aetiology of PSSD, I'm as puzzled by this frustrating condition as anyone else. I'd be very interested therefore to hear from any champions of the 5ht1a theory who might be able to account for my experience or dare I say, propose a solution!

...

So some background...

My name's Alex, I'm now 30 and I was prescribed Citalopram to help me deal with a very stressful time in my life and while I can't say I noted any marked anti-depressive effect, as an anxiolytic I did however find it to be extremely effective. Given that I was single at the time and the sexual dysfunction (as well as flatulence!) I was experiencing were listed as common side effects in the data sheet, I naturally expected everything to return to normal as soon as I stopped taking the drug and persisted in the end for about 2 months.

On taking my first tablet I remember very quickly feeling disorientated, developing a mild tinnitus in both ears and a dry mouth and being unable to stop yawning. By evening the latter three signs had thankfully all disappeared but when I came to masturbate as I used to do at least daily in those days, though still able to achieve erection, I was however disconcerted to find myself unable to cum and eventually gave up trying. By the next day, achieving even a limp erection had become a challenge, but given that my libido and urge to masturbate had also vanished it seemed like something I could live with temporarily (what you don't want, you don't miss!) and so I remained more or less asexual and impotent for the next couple of months.

On stopping Citalopram I would describe my symptoms as follows:
- In the first 3 months... little or no libido, no natural inclination to masturbate and when I tried for curiosity's sake I could muster only weak erections and had extreme difficulty making myself cum - the ejaculations were in case without sensation or force. The useful anxiolytic effects were still present but the flatulence had at least disappeared.
- Approx. 12-15 months later... significant return in the impulse to masturbate such that I will now willingly masturbate for its own sake once a week or more and can ejaculate consistently and quickly through manual stimulation. Erections however are still weak, ejaculation is anhedonic and I'm yet to wake up with morning wood, something which I think occurred pretty much every day prior to starting Citalopram. Anxiolytic effects are probably also still present but more difficult to assess objectively, especially given the time elapsed now.

I've experimented with a variety of proposed treatments without success: maca, horny goat weed, ginko+ginseng, choline, inositol, arginine, yohimbine, ashwagandha, mucuna pruriens, vitamin D and zinc supplementation, loratidine, mirtazapine, cyproheptadine, melatonin and St John's Wort. I tried all of them in isolation over two-week periods with the exception of cyproheptadine (the sedative effects were profound) and SJW (as mentioned above, significantly worsened my symptoms though thankfully for only 1-2 weeks once discontinued).

These days, other than worrying about my dead libido and lamenting my stupidity in taking Citalopram when I really didn't need it, I remain otherwise very fit and healthy. I've never had any hormonal assays performed but given that I'm naturally quite lean and muscular, I've always assumed my testosterone levels are unlikely to be low... though perhaps I'm wrong??

I'm really tempted at this point to launch into a long, pitiful jeremiad about just how crap living with PSSD is but I'm pretty sure everyone here knows that already :D

Re: Rapid onset of PSSD suggests 5ht1a theory wrong??

Unread postPosted: Sat Nov 24, 2018 4:44 pm
by Snake
How theory based only on internet knowledge could be right?

Re: Rapid onset of PSSD suggests 5ht1a theory wrong??

Unread postPosted: Sun Jan 06, 2019 6:20 am
by taarn
For a starter not all SSRIs are the same.
But SSRIs work by raising serotonin levels in your brain by inhibiting SERT. That's an acute effect. Then chronic high levels of serotonin will desensitize your presynaptic 5-ht1a receptors, then since they are not inhibited anymore DRA serotonergic neurons will flood your brain with serotonin, that's when the effect of SSRIs really kick in.

When you take your first pill of SSRI then it elevates levels of 5-HT (serotonin). By taking it continuously you will achieve a steady concentration of the substance that will block SERT in your brain in a specific ratio and specifically elevated levels of 5-HT which will desensitize 5-HT1A over time. But not to forget that 5-HT binds to several receptors and does a lot of things but what is important in this context is that it's mostly anti-sexual, hence causing decreased genital sensitivity, anorgasmia, ED, etc.. MDMA works by a different mechanism but also floods your brain with 5-HT and you'll be having a hard time having sex under the influence of MDMA.

But people have different DNA (not to mention the possible genetic changes) and also have different history of drug use etc.. Drugs are also different and there are just too many variables.
I think 5-HT1A desensitization plays an important role in PSSD but we don't know yet why those receptors and in what extent remain desensitized. Also we don't know too much about the possible long lasting neuroendocrine/endocrine changes.

Re: Rapid onset of PSSD suggests 5ht1a theory wrong??

Unread postPosted: Sun Jan 06, 2019 10:20 am
by lw77
I'm reading one of the articles indicated by Ghost as his bibliography in one of his YouTube videos.

here's the link http://citeseerx.ist.psu.edu/viewdoc/do ... 1&type=pdf

briefly the decreased levels of G-proteins during treatement are present, what i'm asking to you is, if is there some evidence that G-protein's level remaines decreased after treatment.

These are the conclusion of the article:
"There is a tendency for hypothalamic Gi1 ang Gi3 proteins to start returning toward control levels after 22 days of fluoxetine.
Wheter this is a secondary rebound phenomenon that would lead to complete return to control levels upon longer exposure to fluoxetine remains to be examined"
They are sayin' that they don't know if G proteins will return to normal level, am i right?

Re: Rapid onset of PSSD suggests 5ht1a theory wrong??

Unread postPosted: Sun Jan 06, 2019 9:03 pm
by been_too_long
zadig777 wrote:u should forget about 5ht1a throry right away
i suggest u look at properciahelp.com
there u will conclude that many drugs cause same side effects permanently like finasterade,acutane,arimidex, testosterone etc...
so yea,its a wrong theory


We cant forget jack yet other than these theories on things like gut microbes and stuff like pelvic floor issues. Those do not explain a lot of the symptoms. Yet any thing around the bodies chemistry is still on the table. It has to be something that has changed gene expression.. which and what caused it is the question.

In same vein we also can NOT conclude the propercia is related to PSSD in cause. Tout all you want that they share some symptoms. How many pages do you want me to post describing medical conditions with near identical symptoms yet no relation in cause. That is one the problems when comes to medical diagnosis. In absence of a clear cut test that says yes or no (in reality there is few that simple) a medical diagnosis is made just like diagnosing a computer issue... rule out all other causes. Start with everything that could possible explain the symptoms and weed them out one at a time. Until the guys at propercia.com come up with a cure and it works on us... we are dealing with two separate conditions.
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Im in the boat that only two doses did me in. While I get where the OP is coming from it is still not conclusive. Considering the rarity of PSSD can only be explained by something being different in our DNA, we cant know that thing that usually take long term exposure cant hit us right away. Lets say it is a serotonin overdose damaging a receptor (not suggesting it is.. just easy example.) That would take a bit of time to happen in a normal person. But what if we already have high serotonin or a receptor on the brink of being damaged. The SSRI could be just enough to push us over the limit. Drugs can effect gene expression.. that's a fact. What we cant say is a fact is how fast it can happen. Yes it should take long exposure.. but if we are different...

Re: Rapid onset of PSSD suggests 5ht1a theory wrong??

Unread postPosted: Mon Jan 07, 2019 11:38 am
by taarn
The thing is that we have shitloads of variables. We have different genes, people's brain chemistry is also different and we have a different history of previous drug/medicine usage. Unfortunately I have experience with some drugs, mainly stimulants and benzos. For example after taking a single dose of MDMA I had numb genital area for weeks and I never touched an SSRI before. My friends didn't have any problem at all.. Do I have fewer or less sensitive dopamine receptors or did MDMA altered something within my serotonergic system? Or is it the combination? Or something totally different? It's hard to even think in the right direction.

But you can imagine I already had a good chance to develop PSSD so a few pills of mirtazapine was able to fuck me up pretty decently which is supposed to be a lot more benign than SSRIs. I've only read about a few cases it causing long lasting (or maybe permanent) sexual dysfunction. Instead of blocking SERT It works by a different mechanism. It antagonizes alpha2 adrenoreceptors indirectly leading to elevated 5-HT. It blocks some thought to be problematic receptors like 5-HT2C and it directs serotonin mostly to 5-HT1A so it is supposed to have less severe side effects and also has a faster onset. Why is mirtazapine more benign? Is it because of antagonizing the 5-HT2 receptors or is it because it doesn't affect SERT? However I think SERT has to do something with long lasting PSSD.
An interesting read: Regulation of serotonin-2C receptor G-protein coupling by RNA editing. (https://www.ncbi.nlm.nih.gov/pubmed/9153397)
I've also read that researchers were able to reverse PSSD by antagonizing 5-HT2C.

There is also connection between your CNS, neuroendocrie/endocrine system which all have their impact on sexual functioning. I think we can imagine sexual functioning as a multivariable function of these interconnected systems. Our lifestyle, nutrition intake, taking different medicines all have their impact directly and indirectly. I believe that there should be one or more common factors in our genetics that makes us more predisposed to PSSD.
So please do not make these vague statements like PSSD is the same as post finasteride syndrome because we event can't be sure in that different SSRIs and antidepressants are not causing a different kind of sexual dysfunction.