Neurochemical/endocrine deficits behind blunted/flattened affect and ways to treat it?

[Meso]

Blunted affect has been one of the most stubborn symptoms for me to treat. It's also the most debilitating symptom since life has absolutely no taste or meaning when you are completely detached from it as a walking zombie.

NMDA receptor function hypothesis:
From the glutamatergic theory of schizophrenia, NMDAr hypoactivity seems to be implicated, this results in low frontal cortex activation (hypofrontality) and corticolimbic circuit disruption with possible thalamic involvement.

Patients see improvements in negative symptoms (inc. blunted affect) from NMDA-glycine partial agonists such as Sarcosine (full agonists would cause downregulation, I presume).

I tried high doses of glycine and aspartic acid, but they weren't effective. That said, I experience much worse 'flattened' affect when I take Ginkgo Biloba for a week, which may be due to glycine subunit downregulation that it induces.

High doses DXM (dextromethorphan) used to restore my emotions (partially) despite being a NMDA antagonist, but I got tolerant to that effect. It's interesting to note that serotonin releasers and agonists (alpha-methyltryptamine, ayahuasca, Peganum harmala) failed to restore my emotions.
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Estrogen:
Another thing that used to make me hyper-emotional before antidepressant intake was Clomiphene (Clomid). I felt like a girl on her period, I kid you not. Crying over soap operas and superhero movies was embarrassing. But I digress. After getting PSSD, I tried Clomid, but I didn't experience any emotional boost, my reaction to it is completely lost.

My theory? if progesterone is high, it interferes with estrogen receptor function, despite normal or supraphysiological level of estradiol.
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Dopaminergic windows:
I was prescribed Methylphenidate for a while, and I experienced a partial response window. I became very sociable and many emotions were improved, but not all of them.

I also tried a very high dose Venlafaxine (my poison) before. Around the 600 mg mark, where it becomes a weak DRI. I felt jealously and infatuation for the first time in years, but of course it was short lived and I went down back again to my normal dose back then.

Nicotine, which is also heavily used by schizophrenic patients to combat negative symptoms, also restored many emotions while being on Venlafaxine. However, I lost response to it after quitting Venlafaxine and getting PSSD.

Tonic dopaminergics (MAO-B inhibitors and dopamine agonists) were ineffective.
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GABAergic windows:
Baclofen was perhaps the most potent agent to combat blunted affect for me. It made me even more emotional than my pre-antidepressant level, similar to Clomiphene before SRI intake. It also improved anhedonia and libido a ton.

I eventually became tolerant to it and taking it now just makes me too sick. I read recently that Baclofen affects GnRH and LH mRNA expression, but my reaction was more acute. Perhaps its ability to increase cortisol and striatal dopamine level?

Another window happened with Gabapentin (and Levetiracetam on a different occasion), both of which restored my emotions greatly for a single day.
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Serotonergic windows:
Trazodone and Mirtazapine were able to restore my emotions, but only for a single day each, as well.

SJW restores my emotions (partially) when dosed, but this happens randomly, and within a couple of hours I get even worse blunted affect and anhedonia. Chronic intake makes my emotions extremely blunted and anhedonic.
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Random window:
I dosed glutamine + creatine + caffeine and got a window of full emotionality while I was still on Venlafaxine. It was beautiful, I listened to music all day and felt mesmerized by it. It was gone after I had to dose Venlafaxine. I managed to get a second window on this combination on a different day, but after that it never happened again.
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Buttomline:
This symptom is driving me crazy. I tried so many things for it in vain. I've managed to achieve partial recovery from PSSD with improvements of 50-100% across all other symptoms, but this particular one? I can't even get a 10% relief for more than a day. Any help?

[mrstaircase]

I'm currently cruising on creatine (DHT), boron (lowers SHBG), nicotine (3a-hsd inhibitor) vaping, caffeine and schisandra (Ca(2+) channel, cortisol modulator). Feels way too good though so I'm kind of expecting to go down soon. You could give nicotine a try if you want to inhibit 3a-hsd, I don't find it addictive in the pure form (gum or vaping) but your experience may vary

[raven100]

Lol zadig maybe give your protocol a test run before you start selling it as the answer

[been_too_long]

im giving it a run its not helping cause i dont respond to drugs
those who respond to drugs will benefit from it im pretty shure

I don't respond to drugs.... that is quite blanket statement don't you think? Im going to skip over the fact it is biologically impossible to not respond to certain drugs. I wont even point out that if you don't respond to drugs... SSRI is a drug.... you wouldn't have PSSD. I mean a positive or a negative is still a response...

Ill probably get censored for saying it and at this point I really do not care. I was born with a tough leathery ass no one here can chew thru. Your theories flip flop worse than a meth smoking fish out of water. You have suggested things that could literally kill people. You do not have the knowledge, experience nor credibility to be designing some treatment plan that doesn't even have pseudo-science to back it up. I would again remind you that your not a doctor and need to stop telling people what (and what not) to take, but it has flown over your head too many times to be worth the effort.

And for the record.... if a "protocol" or whatever we are calling it today, does not work on the vast majority of us... it is not a treatment, much less a cure for PSSD. One or two people claiming improvement doesn't come close to meeting NNT. Maybe you should familiarize yourself with the term.

[Snake]

im giving it a run its not helping cause i dont respond to drugs
those who respond to drugs will benefit from it im pretty shure

I don't respond to drugs.... that is quite blanket statement don't you think? Im going to skip over the fact it is biologically impossible to not respond to certain drugs. I wont even point out that if you don't respond to drugs... SSRI is a drug.... you wouldn't have PSSD. I mean a positive or a negative is still a response...

Ill probably get censored for saying it and at this point I really do not care. I was born with a tough leathery ass no one here can chew thru. Your theories flip flop worse than a meth smoking fish out of water. You have suggested things that could literally kill people. You do not have the knowledge, experience nor credibility to be designing some treatment plan that doesn't even have pseudo-science to back it up. I would again remind you that your not a doctor and need to stop telling people what (and what not) to take, but it has flown over your head too many times to be worth the effort.

And for the record.... if a "protocol" or whatever we are calling it today, does not work on the vast majority of us... it is not a treatment, much less a cure for PSSD. One or two people claiming improvement doesn't come close to meeting NNT. Maybe you should familiarize yourself with the term.

The truth has been spoken...

[jjr81]

I don't respond to drugs since my PSSD "crash" either. Viagra and Cialis don't work, marijuana doesn't get me high, alcohol doesn't get me drunk, etc. So it is biologically possible not to respond to drugs if the pathways are blocked. Or if the receptors are dead. I also don't get tired, hungry, or feel any emotions. None of this shit seems like it should be possible. Yet here we are.

[lw77]

Guys we are here to help us, this forum must serve as a meeting point, an exchange of information and support. It is useless to clash and insult.
Let's use our energies for useful efforts.

[sovietxrobot]

hi, I see a lot of similarities to my own story here. venlafaxine was poison for me as well, and I definitely felt some hormonal effects- weight gain, night sweats, joint pain, weakness, etc. I also had a totally flat affect, inability to initiate, anhedonia, and severe brain fog. I have had a lot of success with dopamine agonists. Wellbutrin restored some concentration and interest, but it was mucuna pruriens/dopa mucuna that really cured me. research has shown it to be at least as effective as levodopa in treating Parkinson's disease, so I have been taking 1g a day and its fantastic. I'm interested in all my hobbies again, concentration and initiation are back and sometimes even better than before. its definitely helped with my PSSD as well.

[TalkingAnt]

sovietxrobot,

Great to hear you are doing better. Could you let us know the brands and dosages of what you are currently taking, and for how long? Thanks!

[been_too_long]

Guys we are here to help us, this forum must serve as a meeting point, an exchange of information and support. It is useless to clash and insult.
Let's use our energies for useful efforts.

Ok let me hit a few bullet points here.

I didn't speak my true feelings and call him a idiot. That would be a insult. I said anyone that follows would be the idiot. So.. no insult except to hypothetical people.

This is not a "clash" of personality nor a "clash" in theories. This is directed at facts. He HAS proposed use of drugs that CAN kill. For no other reasons than I think so. So yeah, that's dangerous. He has told people on numerous occasions to stop taking meds prescribed by their doctors. He is qualified to do so? Does he have any medical knowledge past reading WebMD to be countering what a doctor prescribes. So yeah, that's dangerous. I do not feel guilty about warning others.

His protocol... <shrugs> I don't know how if it has any potential because see no reason to delve into it.. that funny little lack of credibility and the fact there is no real science to suggest it. Claiming "Im sure" it will work means jack shit in science. Until it has been tried and worked... tried by another and worked.. tried by yet another.... it is nothing. A treatment that can not be reproduced, is NOT a treatment. We don't even have one success.

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People saying no drug will work on them is shakey at best. Your telling me that no matter how much cocaine they take, their heart and breathing does not increase? I call bull on that. A person can claim "I don't get stoned" or "I don't get drunk." Hard to argue that since its based on a persons perception. But... I can guarantee not a person here that says that, has gone to a medical professional while under the influence and had the proper test done to evaluate reflexes or mental faculties. How many drunks have said they are not impaired; then go out and kill someone in a wreck? Once again, all about perception. For the record "I can drink any amount of alcohol and not get drunk" is not a fact till you are laying in a ER on deaths door due to alcohol poisoning. Get to that point and still be able to pass a battery of sobriety tests.. Ill admit to being dead wrong.

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I have been called out a few times for being overly skeptical. There is a funny little thing about that... its seems Ive been right. Lets take two examples... antifungal thread- I was called out a few times in it. Result- OP updated and stated nobody should try it. Fecal transplant... once again called out. Result- its been several months; can I see the show of hands of all the people that tried it much less was cured?????? I mean, people acted like it was the holy grail for us. Why didn't all you people try it?

Just because you don't like the way I state things, does not make the statements incorrect. Im overly blunt, don't understand the concept of sugar coating, and do not hesitate to hurt peoples feeling. That doesn't make me wrong. An asshole perhaps but not wrong. I can live with being called that. Have done so all my life.

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These forums have been here for how many years? How many years with the attitude of screw all them bullshit doctors.. screw real science... I will figure it out my way? If it is working then why do these forums still exist???????????????????????????

There is a lot of people that scream for a study into PSSD. Hey, at least that's a bit of science. Problem is at this point its pretty much impossible. Not even getting into the cost; but where do they start? We cant even agree on hallmark symptoms. Ive seen everything on this forum from PSSD causes hemorrhoids, bush eyebrows, headaches after workout, list goes on and on.. You think we can walk in front of a panel of experts with 1000 different symptoms and get anything but shrugs and head shaking? Hell, Ive see it declared the drugs that are not even SSRIs can cause PSSD. Naw... that's not confusing when presented.

For the record; according to my inbox, Im not the only one that feels this way. There is multiple other people that agree. Im just the only asshole that will publically state it.

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Look, my ego can take the hit of being wrong. Id actually love to be wrong about everything I feel and say. Id love to open the page one day and find out someone has stumbled upon the magic bullet we are so desperately after. It hasn't happened in all these years.... someone fucking prove me wrong. Until than, my money is still on science finding the answer.