Attempting to cure/reverse my own PSSD

[Meso]

Short update:
I've been feeling extremely terrible due to Vortioxetine's adaptation phase. I feel ill with general malaise, which is called "leaden paralysis", and it's very hard just to walk around. I spend a lot of time to get out of bed and my body aches so much. There's a sense of excessive fatigue and drowsiness. Other symptoms I'm having are anhedonia and irritability. I don't have the motivation to talk to anyone or do anything. I also have zero libido, but morning and random erections are back again. Overall, symptoms are getting just a little better every day, so there's 5HT1A autoreceptor desensitization happening.

Presynaptic 5HT1A agonism would do that, since it would worsen symptoms of depression, so I was expecting this. I just wasn't expecting it to be this bad. It's near intolerable. This is the 9th day on Vortioxetine and clinically relevant desensitization of presynaptic 5HT1A takes up to 4 weeks or 6 weeks in worst cases.

I've changes my dosing a little:
- Vortioxetine (5 mg): No change here.
- Metformin (500 mg): To minimize elevation of SHBG and lowering of cortisol.
- Memantine (20 mg): Back to taking this, explained later.
- Baclofen (12.5 - 25 mg): 50 mg is a bit much with Memantine. 12.5 mg is better.
- Mesterolone (Ditched): After lowering Metformin, I don't think I need this one, and I'd rather not take more than 4 drugs. I'll test my SHBG after adaptation to Vortioxetine and add this back if need be.

I've re-added Memantine to augment Baclofen, and to bring into this cure attempt my theory regarding turning Memantine into Ketamine effect-wise with boosting BDNF and TrkB through Metformin. It may not work since there wouldn't be enough AMPA upregulation/activation as Memantine would increase NMDA antagonism-mediated glutamate disinhibition only mildly (compared to Ketamine's potent closed-channel NMDA antagonism), but here's hoping that Baclofen's rebound effect on glutamate would be enough. It's all trial and error.

[AnhedonicApe]

Hey man, very courageous of you to do this. Good luck

[Snake]

Hey man, very courageous of you to do this. Good luck

I believe that sooner oraz later he'll succeed, it's also possible for you.

[voyteck]

I feel ill with general malaise, which is called "leaden paralysis", and it's very hard just
to walk around. I spend a lot of time to get out of bed and my body aches so much. There's a sense of excessive fatigue and drowsiness. Other symptoms I'm having are anhedonia and irritability. I don't have the motivation to talk to anyone or do anything.

You're having so many symptoms common with my pre-ADs period (and some more regarding my state now).
But I am especially interested in this "Excessive fatigue and malaise. I feel "ill" - cause it's been the main reason I started ADs many years ago and became disabled person eventually. Should you - Mesolimbo or anyone else - have any hypothesis about what is involved (apart from general CFS), I'd be grateful for any tips. I don't want to hijack this thread, so you can post in my: http://www.pssdforum.com/viewtopic.php? ... 1&start=10.

[nebonym]

Short update:
I've been feeling extremely terrible due to Vortioxetine's adaptation phase. I feel ill with general malaise, which is called "leaden paralysis", and it's very hard just to walk around. I spend a lot of time to get out of bed and my body aches so much. There's a sense of excessive fatigue and drowsiness. Other symptoms I'm having are anhedonia and irritability. I don't have the motivation to talk to anyone or do anything. I also have zero libido, but morning and random erections are back again. Overall, symptoms are getting just a little better every day, so there's 5HT1A autoreceptor desensitization happening.

Wow, I didn't expect to find some else make a description of what sounds like the same weird feeling I have been having lately. So I tried a diet with minimal tryptophan content (less than 200mg/d) with great amounts of BCAA with every meal. After the third day this feeling of excessive fatigue, drowsiness and feeling heavy resulting in difficulty moving the arms and legs suddenly appeared. It scared me enough to hold back from the diet, but the "leaden paralysis", if that is what it is, still persists after a couple of days. Do you believe we could have the same symptoms and do you have an opinion whether going back to the diet would alleviate it better?

[TalkingAnt]

Hang in there Meso, we are all rooting for you!

[Meso]

I'm sorry, I won't be able to read other threads or visit the forum much until I get past the adaptation phase and feel better.

The fatigue, malaise and feeling ill are the effects of cytokines release such as IL-2, IL-6, TNFα, NF-κB, etc. It's the same response you get when you have the flu, because the body secretes these cytokines to attack the viruses. In depression, cytokines are significantly elevated triggering this leaden paralysis and malaise without having the flu or an autoimmune disease.

In my case, presynaptic 5HT1A supersensitivity (or abnormally increased density) would cause less activation of postsynaptic 5HT1A, resulting in less beta endorphin and cortisol release. This leads to aggravation of any autoimmune or inflammatory conditions, since endorphin and cortisol suppress the immunity.

With Vortioxetine, I get an even less activation of postsynaptic receptors during the adaptation period, significantly increasing my autoimmunity and cytokine release. I happen to have a low grade rheumatoid arthritis to begin with.

[Jaxx]

i have no experience with vortioxetine myself, but im surprised it hits you this hard, but you already expected it would. Hang in there!

[voyteck]

The fatigue, malaise and feeling ill are the effects of cytokines release such as IL-2, IL-6, TNFα, NF-κB, etc. It's the same response you get when you have the flu, because the body secretes these cytokines to attack the viruses. In depression, cytokines are significantly elevated triggering this leaden paralysis and malaise without having the flu or an autoimmune disease.

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.

[Meso]

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.