why i think 5ht1a desensitiation theory is wrong.

[jaiho]

I don't buy the 5ht1a AR desensitiation theory due to my own personal experience, as well as many people having recovered with a completely knocked out 5ht1a AR.
People regain sex drives due to years of depression, and if we use the current theory here that 5ht1a is permanently knocked down, increasing overall serotonin, then that would mean millions of people would have neutered sex drives while on SSRIs, which simply isn't true. Infact, many people get more sex drive after starting a pure SSRI.

So, there is a minority among us with perhaps a genetic defect that causes underactivation of post synaptic 5ht1a, which facilitates mid brain & prefrontal cortex dopamine transmission, as well as increased activation of 5ht2c receptors, which further reduces dopamine transmission.

SSRIs can cause frontal lobe apathy in some people, which is where we need more activity for sexual function.

The harm to sexual function from SSRIs is generally due to underactive post synaptic 5ht1a, in combination with overactive 5ht2a+c receptors.

So what we need to do is increase 5ht1a post synaptic transmission, and antagonise 5ht2a & c.
And to remove the variable of depression, the addition of SRI & NRI.

So my recommended combo is, Trintellix + Nortriptyline.

Trintellix is an SSRI with 5ht1a agonist properties.
Nortriptyline is an NRI with potent 5ht2a & c antagonist properties.
With these two together you would get a huge increase in mid brain, and prefrontal cortex dopamine, as well as via NE pumps.

If you absolutely want to avoid SSRIs, then Buspar + Nortriptyline could be decent, in theory.

[jaiho]

And to add another thing, the genital numbness, and pure orgasmic anhedonia i had prior to my current combination (Prozac + Nortriptyline) proves my theory. As well as other anecdotes i've read about people who used Zoloft purely to increase their orgasmic pleasure.
Choosing the right drugs for your neurochemistry is critical for a positive outcome whether your PSSD is caused by depression or exacerbated by SSRI exposure.

[Foxx]

Yeah, always it could be.

I have some quetions also, why ours (I assume) body temperature is lower. According to some researches best way to estimate 5-HT1AR function is to measure its response to agonist, the bigger drop in temperature the more responsive 5-HT1AR is. However I've read also that mice "treated" with neurotoxin with affinity to serotonergic neurons have problems in cold environment with keeping their body temp at normal, so it's not clear.

Second is about 2A/2C antagonists which are really helpful. My fav obviously is Mianserin. It brought back dreaming at once, disinhibited dopamine, turned on balls. From my personal experience Mianserin>>Buspar

Third is about estrogen receptors and Clomid, which is awful, is it about serotonin which Clom increases or estrogen receptors..

Fourth is why people on SSRIs don't have sexual dysfunction from very day 1 of treatment, since SERT is occupied at well..90%, even after two weeks when everything is downregulated and stuff is desensitized they're doing fine.

Fifth is why maois are amazing for a couple of days only.

Well..I don't know for sure. What I know I have some problems with serotonin clearance, I'm allergic to even mild spikes in serotonin levels. LSD which increases serotonin was horrible, I have disastrous two weeks afterwards with anxiety and no-dick. In SERT knockout models mice have "lower levels" of serotonin, wiki site reported that tryptophan hydroxylase is downregulated(!), neurons firing rate is lower(!), however there is more (or less?) serotonin in the synaptic cleft and when given serotonergics it skyrockets. Overall sert, net and dat are "master proteins" more important in neurotransmitter homeostasis than receptors I've read, 5-HT1A is overrated, but only a little, kind of when having jaundice not your skin is faulty, but the liver. So we have to treat liver, however treated successfully skin alone could mean treated liver also

Imo SERT is the culprit. When on SSRIs your serotonin level is higher and that keeps "machine" kind of working. Serotonin alone is necessary for "activating" SERT, less serotonin means less SERT. When you're going cold turkey synaptic serotonin decreases which downregulates SERT further, however some of it is released. Kind of 5-HT1A is very weak and easily goes desensitized also. Because of SERT? Some studies states that this could be true.

It's a matter of discussion and thanks for this topic. However..

..one thing I know I will never go back to SSRIs, nor other prescription serotonergics. I don't care if they're going to bring back mood and stuff. Poison is still poison. Imo it's very possible that they're bring back to life in combos for a high price of being damaged further. Brintellix for example. It's a SSRI undercover advertised as a "modulator" my psy lied it's not a SSRI. Really? It improved my symptoms due to strong 5-HT1A agonism, but at the same time messed with my brain as any other SSRI.

Overall, no thanks. I know that serotonin reuptake inhibitors sucks in any form. Soon will be my first neurofeedback session after long break and this is only one vialable I hope way to turn on, or improve electrical functions of frontal lobe. Really looking forward into it. I hope it will be ok regarding depersonalization.

Are you doing better drug free? Are your baseline improving when off drugs? That's the most important questions. Also I am really afraid of polydrugging. Best way to go insane, next will be some small innocent benzo for lingering aniety, etc, etc..

Just no.

[Foxx]

I was damaged by Zoloft. Tried it a half year after stopping my treatment, at the second, third day I had explosive orgasm, true, but without proper erection and with numbness, afterwards there was aniety. This is a deception man. This is not healing by any means. Microdosing and tapering? Well.. that could be something, but regular dosing is a suicide.

https://www.youtube.com/watch?v=ARZ2Wv2BoFs

Smart guy.

[jaiho]

If you take Brintellix alone, you're still getting 5ht2a /c activated, which can make you feel worse.
It entirely depends on your neurochemistry. You might only need a certain SSRI to make you feel normal again, or an MAOI, or an SNRI.
I know certain SSRIs make me feel god damn awful. Numb, zombie like. Impossible to orgasm.
If we look at everything on paper, we still dont understand, or will never understand the functions behind this. It's mostly plausible that it's caused by depression, going by my own experience. I have literally felt, off meds, numb genitals, and as soon as i get on the right SSRI, all my feeling comes back, and not just physically, but emotionally too.

[Foxx]

Are you going to taper off that stuff?

[Coraggio]

Yeah, always it could be.

I have some quetions also, why ours (I assume) body temperature is lower. According to some researches best way to estimate 5-HT1AR function is to measure its response to agonist, the bigger drop in temperature the more responsive 5-HT1AR is. However I've read also that mice "treated" with neurotoxin with affinity to serotonergic neurons have problems in cold environment with keeping their body temp at normal, so it's not clear.

Second is about 2A/2C antagonists which are really helpful. My fav obviously is Mianserin. It brought back dreaming at once, disinhibited dopamine, turned on balls. From my personal experience Mianserin>>Buspar

Third is about estrogen receptors and Clomid, which is awful, is it about serotonin which Clom increases or estrogen receptors..

Fourth is why people on SSRIs don't have sexual dysfunction from very day 1 of treatment, since SERT is occupied at well..90%, even after two weeks when everything is downregulated and stuff is desensitized they're doing fine.

Fifth is why maois are amazing for a couple of days only.

Well..I don't know for sure. What I know I have some problems with serotonin clearance, I'm allergic to even mild spikes in serotonin levels. LSD which increases serotonin was horrible, I have disastrous two weeks afterwards with anxiety and no-dick. In SERT knockout models mice have "lower levels" of serotonin, wiki site reported that tryptophan hydroxylase is downregulated(!), neurons firing rate is lower(!), however there is more (or less?) serotonin in the synaptic cleft and when given serotonergics it skyrockets. Overall sert, net and dat are "master proteins" more important in neurotransmitter homeostasis than receptors I've read, 5-HT1A is overrated, but only a little, kind of when having jaundice not your skin is faulty, but the liver. So we have to treat liver, however treated successfully skin alone could mean treated liver also

Imo SERT is the culprit. When on SSRIs your serotonin level is higher and that keeps "machine" kind of working. Serotonin alone is necessary for "activating" SERT, less serotonin means less SERT. When you're going cold turkey synaptic serotonin decreases which downregulates SERT further, however some of it is released. Kind of 5-HT1A is very weak and easily goes desensitized also. Because of SERT? Some studies states that this could be true.

It's a matter of discussion and thanks for this topic. However..

..one thing I know I will never go back to SSRIs, nor other prescription serotonergics. I don't care if they're going to bring back mood and stuff. Poison is still poison. Imo it's very possible that they're bring back to life in combos for a high price of being damaged further. Brintellix for example. It's a SSRI undercover advertised as a "modulator" my psy lied it's not a SSRI. Really? It improved my symptoms due to strong 5-HT1A agonism, but at the same time messed with my brain as any other SSRI.

Overall, no thanks. I know that serotonin reuptake inhibitors sucks in any form. Soon will be my first neurofeedback session after long break and this is only one vialable I hope way to turn on, or improve electrical functions of frontal lobe. Really looking forward into it. I hope it will be ok regarding depersonalization.

Are you doing better drug free? Are your baseline improving when off drugs? That's the most important questions. Also I am really afraid of polydrugging. Best way to go insane, next will be some small innocent benzo for lingering aniety, etc, etc..

Just no.

I don't think 5ht-1AR is wrong. I think it' s only a little part of the problem. We have SERT and thryptophan hydroxylase down-regulated. That means we have less serotonin synthesis and prolonged serotonin on the synaptic cleft. In addition we have every 5-ht receptor desensitized. So we have poor activation of firing negative feedback ( 5-ht1AR and 5ht1BR ) and poor activation post synaptic side but with higher amount of serotonin in the synapsis. The net effect I think could be a disreguleted firing quality: less serotonin is released but continuously and remains more time in the synaptic cleft becouse less amount of SERT. If we think a synapsis firing as a binary system we don't have a fine release of serotonin anymore. Maybe this leads to impossibility 5-ht resensitation or SERT upregulation. This is only my idea.

Curiously: my older brother took SSRI+ benzos at higher doses and for a longer period than me. I ' ve took SSRI only a smaller doses. He doesn' t have PSSD. I can only think benzos played a protective role for him.

[LEON86]

how to take these two meds? dosage and for how long time?

[jaiho]

Are you going to taper off that stuff?

Nope. it recovered my sex drive & physical pleasure. If i go off the drugs, i have numb genitals and no pleasure and im anhedonic

[jaiho]

how to take these two meds? dosage and for how long time?

First you find the SSRI compatible with you. I use prozac, 20mg, add Nortriptyline 10mg for 1 week, go up to 25mg and stay there.
Prozac triples the Nortriptyline blood level, which the ideal theraputic range is 75-100mg. So with prozac, you only need 25mg generally.

With Zoloft or Luvox, you start at 25mg then build up to 75mg.

Zoloft is the best first choice if you've never used it.