Attempting to cure/reverse my own PSSD

[AnhedonicApe]

I'll consider it as response to my question.
Yes, I read about cytokines in depression. That's why about 3 years ago I checked some of them (the only panel available): IL-1 beta, IL-6, IL-8, IL-10, IL-12, TNF-alfa - all OK. On one hand, I was also on clomipramine 40 mg (I read some ADs could influence cytokines), on the other hand, this drug didn't make any difference in my exhaustion and malaise.
I just wish I could check other cytokines too, but didn't find any more commercial test, yet.

Another thing that can cause fatigue and malaise is thyroid resistance (high reverse T3) or hypothyroidism.

I'm starting to feel better today. Libido is increasing noticeably and I'm craving women somewhat. But I'm also feeling anxiety and GAD. My mood has improved significantly, but I just have an unexplained fear of the future (GAD). It seems like today is the first day of clinically relevant downregulation of presynaptic 5HT1A. Malaise is also down a bit, but overall I'm still feeling out of it. I expect my symptoms to become better and better over the next couple of weeks.

Seriously great to hear you are getting out of the pit. I understand ur feeling about GAD, i have the same stuff waiting for me on the other side. I always try to remember that living with emptiness is worthless in every possible way, where living with anxiety has good moments. Good luck next week!

[Snake]

Mesolimbo!

I would like to ask few things about vortioxetine:

1) Why some people on the forum tried it and it didn't help them at all?
2) What to expect from it after those few hard first weeks?
3) Should it give me my sexual functions back?
4) Is it ADs connected with some symptoms like difficulty with reaching orgasm while taking it?
5) What about tolerance? Can we take it for months/years with sustaining the same effects?
6) For example, should I take take it alone or combined with another drug/drugs?

[Meso]

1) Why some people on the forum tried it and it didn't help them at all?

Different types of PSSD. My type of PSSD is presynaptic 5HT1A supersensitivity. If a person tries 50 mg baclofen and feels much better, then his problem is also presynaptic 5HT1A.

2) What to expect from it after those few hard first weeks?

Baclofen-like effect without tolerance or crash. On top of this, presynaptic 5HT1A receptors are anti-erections, so it would improve erectile function (through downregulation). Vortioxetine is also pro-glutamatergic, so no need for nootropics and cholinergics.

3) Should it give me my sexual functions back?

All except for orgasmic intensity. For that one would need pro-oxytocin stuff like fenugreek, 3g vitamin C, and magnesium. I don't mind orgasmic intensity, though.

4) Is it ADs connected with some symptoms like difficulty with reaching orgasm while taking it?

No, it's the least associated with sexual side effects (on par with Bupropion). I reached orgasm on it without a problem and it's improving my erectile function and libido at this low dose (5 mg only). No loss of genital sensitivity so far.

5) What about tolerance? Can we take it for months/years with sustaining the same effects?

Yes, it isn't like Baclofen. It increases tonic activity of postsynaptic 5HT1A. If there's any sign of tolerance, I'll add SJW (Saint John's Wort upregulates postsynaptic 5HT1A receptors).

6) For example, should I take take it alone or combined with another drug/drugs?

I currently take it with a low dose Baclofen and Memantine to downregulate GR. After a few months, I'll remain on Vortioxetine + 1 other drug, probably Metformin. This is my plan.

I suggest that you wait a bit for my adaptation to Vortioxetine before trying it yourself. Wait for a a week or two, bro.

[Jaxx]

1) Why some people on the forum tried it and it didn't help them at all?

Different types of PSSD. My type of PSSD is presynaptic 5HT1A supersensitivity. If a person tries 50 mg baclofen and feels much better, then his problem is also presynaptic 5HT1A.

anything else that would give this clue? Only few have tried baclofen so-far, would a positive reaction to SJW for instance mean something for pre-synaptic activity?
Is postsynaptic desenzitation always connected to presynaptic sensitivity?

[Meso]

anything else that would give this clue? Only few have tried baclofen so-far, would a positive reaction to SJW for instance mean something for pre-synaptic activity?
Is postsynaptic desenzitation always connected to presynaptic sensitivity?

SJW also upregulates 5HT2, so yes it's pro-oxytocin as well and would point towards a positive reaction to postsynaptic 5HT1A receptors activation.

Presynaptic 5HT1A are autoreceptors, so abnormal sensitivity of them would mean postsynaptic 5HT1A receptors aren't getting activated and are muted/inhibited.

Another thing that would give a clue is MDMA, but that's a bad idea since it would downregulate postsynaptic 5HT1A since it releases serotonin too much. Baclofen is like a mild MDMA, or MDMA-lite, and it can still cause desensitization and tolerance without Memantine/Fasoracetam.

[Meso]

Update:

Today I'm feeling a TON better, very close to how I felt before PSSD. I woke up extremely horny to the point of seeking unplanned sex with my partner. My anhedonia is completely gone and I'm having musical earworms again. I feel alive as blunted affect is also greatly reduced.

That said, I'm still not adapted, since I still experience physical and mental fatigue (albeit a lot less than 2 days ago). I feel moderate to severe GAD and worrying excessively about the future for no reason, which is a sign of high 5HT1A activation. Still need to adapt further to Vortioxetine. I believe in 2 weeks time I'll be done.

Overall, I feel even better than my 6-drugs symptomatic relief despite of partial adaptation. Now I'm certain that my type of PSSD is presynaptic 5HT1A supersensitivity/increased density.

This wouldn't be possible without the other 3 drugs. It's not just Vortioxetine, but also BDNF/TrkB boost from Metformin, GR downregulation from Baclofen, and glutamate release from Memantine.

[Jaxx]

Update:

Today I'm feeling a TON better, very close to how I felt before PSSD. I woke up extremely horny to the point of seeking unplanned sex with my partner. My anhedonia is completely gone and I'm having musical earworms again. I feel alive as blunted affect is also greatly reduced.

That said, I'm still not adapted, since I still experience physical and mental fatigue (albeit a lot less than 2 days ago). I feel moderate to severe GAD and worrying excessively about the future for no reason, which is a sign of high 5HT1A activation. Still need to adapt further to Vortioxetine. I believe in 2 weeks time I'll be done.

Overall, I feel even better than my 6-drugs symptomatic relief despite of partial adaptation. Now I'm certain that my type of PSSD is presynaptic 5HT1A supersensitivity/increased density.

This wouldn't be possible without the other 3 drugs. It's not just Vortioxetine, but also BDNF/TrkB boost from Metformin, GR downregulation from Baclofen, and glutamate release from Memantine.

Thats some pretty awesome news! To what extent is this situation different than your previous relief?

[Meso]

Thats some pretty awesome news! To what extent is this situation different than your previous relief?

Back then, I would get anhedonia and blunted affect relief as long as I'm under the effect of Baclofen, and when it's out of my system I would crash. Now on Vortioxetine, the benefits seem to be integrated into my baseline, without feeling like I'm under the effect of something, or "on" something, so to speak. Therefore, I only dose Baclofen once, for its ability to release ACTH, and not particularly for its ability to ameliorate anhedonia/blunted affect as much. The situation is better.

[kali]

Awsome !! you'r our hope Mesolimbo.......

Appreciate your help.... you are helping so many guys.

[Jaxx]

Million dollar question, you expect presynaptic sensitivity to normalize or always go back to pre-ssri baseline when/if coming off?