Low Dose SSRI (Reinstatement)

[Skorpio]

Ok, since I see we are reviving this idea I will share a glimpse of what i think. First of, I don't want to be a smartass since we all are in the same boat but...
Basically, i thought that main problem is dopaminergic pathway mediated not only by 5-HT1A but by 5-HT2A, HT-2C, 5HT-4, 5-HT6, and 5-HT7. It goes from VTA to the limbic and cortic pathways mediated by many receptors.
See this: https://en.wikipedia.org/wiki/Serotonin#Receptors
5-HT6 98.41 Cognition (antagonists ↑); antidepressant effects (agonists & antagonists ↑); anxiogenic effects (antagonists ↑[25]). Gs signalling via activating adenylyl cyclase.
5-HT7 8.11 Cognition (antagonists ↑); antidepressant effects (antagonists ↑). Acts by Gs signalling via activating adenylyl cyclase.

5-HT4, 5-HT6 amd HT7 are upregulated INDIRECTLY, and they ALL affect monoamines, so there's another thing going. And I think it's linked to the phenomenon called Hormesis. I tested it with methylphenidate and it works - taking 50mg in the span of few hours and two 1mg doses stimulated me excessively for 3 days - bad idea if you ask me. However, here's the BEST part: SSRI's from ALL sources that i know, are LOWERING serotonin, not raising. And they lower it by 80-90%. And guess what ? Some article mentioned 5-HT2C in the first 3 weeks upregulated by 90%. Concidence ? I think not. Now, with methylphenidate, taking 1 mg probably lowered my dopamine levels which temporarily upregulated receptors. So, when you are on SSRI, you have lowered serotonin AND up-regulated receptors - brain has homeostasis. However, when you abruptly quit the medication, your serotonin levels are backing up to normal with oversensitized receptors. Many people have symptoms of overactivity of certain serotonin receptors when quiting -
nausesa and loss of apettite -> 5-HT2C,
muscle pain, nausea again - 5-HT3 ? from wiki
CNS: nausea and vomiting center in brain stem, anxiety,[24] seizure propensity [25]
PNS: neuronal excitation (in autonomic, nociceptive neurons), emesis[24]
headache at frontal lobe - 5HT-6 and 5-HT7 ? LSD and associated psychedelics are known for curing migranes, headaches and guess what ? Always when i took acid and it worked (that is, low level ssri in blood while taking it), it alleviated headache AND i had full emotions and usually (but not always) libido was back. So THIS is way i came vack to the medication - acid was the first thing i tried but it DID NOT cure me and i don't recommend taking this because for me it was hit or miss - more of a hit but i don't know whether it could fuck you up. However, it gave hope as i said, since there was nothing damaged.
Some, my 2 cents. Right now I have literally no anxiety (i took ssri for that), i can laugh, have virtually zero brain fog, sexual functions SEEMS to be well stabilizing, have occasional zaps. As is said, i will report changes
All the best

[Coraggio]

continuing...

ssri affect allopregnanolone production https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23979/
We don't know how, but maybe in some people SSRI are causing a disruption in this mechanism even after quitting it. Well, I guessed in my last post that maybe we're lacking allopregnenolone, but this is just a guess. Maybe it's too little, or too much allo...
So, going back to ssri and taking it correctly could help... I also suggest don't letting your brain without the medication (if you're taking it). Once you're taking ssri, u should wean off SLOWLY. btw, a ssri that has a long half-life would be the best (like fluoxetine), and taking it more than 1 time in the day makes sense, as Skorpio reported. My low libido didn't started after I quit SSRI, I can't remember exactly when it started, but I started to feel this after a few months in the medication. I must say I was taking fluvoxamine and it has a short half life.

This syndrome is probably connected to PFS sufferers, cause 5α-reductase mediates allopregnanolone synthesis. As we know, Proscar strongly inhibits 5α-reductase.

Yes, in fact we have already noted this connection with PFS. Melcangi is going to study brain neurosteroid levels in brain PSSD rats. And also serotonin and dopamine levels. Now I am trying to convince him to study also the gaba A receptor subunits.
PTSD, a persistant psychiatric syndrome with longlasting effects, shares with pssd one thing: allopregnenolone withdrawal/tolerance. Acute/prolonged extreme fear induces an allopregnanolone spike and this is shared by SSRI action too. Both Cronic allopregnanolone both acute sudden allopragnone withdrawal downregulates alpha4receptor subunit in gaba A receptors. I think that a prolonged SSRI treatment or an acute SSRI cold turkey withrawal can create this huge SHIFT in subunit receptor conpositions so this can lead to a different receptor affinity in many areas and so to a different brain networks.

Gaba A receptor are massively importantvin many different brain areas because Gaba has 33% of all brain synapses and gaba A is the most prevalent gaba receptor.

[jaiho]

Ok, since I see we are reviving this idea I will share a glimpse of what i think. First of, I don't want to be a smartass since we all are in the same boat but...
Basically, i thought that main problem is dopaminergic pathway mediated not only by 5-HT1A but by 5-HT2A, HT-2C, 5HT-4, 5-HT6, and 5-HT7. It goes from VTA to the limbic and cortic pathways mediated by many receptors.
See this: https://en.wikipedia.org/wiki/Serotonin#Receptors

Good post.
SSRIs feel like absolute shit in the first 3 weeks, likely because of what you've just stated, 5HT2C for example, is critically important for libido, and pleasurable feelings. It needs to be downregulated, but sometimes SSRIs keep dopamine inhibited for whatever reason. It's likely a mix between 5HT2C and DAT.
This is why when i added a strong 5HT2C antagonist to an SSRI, it most of the time restores the loss of dopamine. But its not the only part of the puzzle, The dopamine transporter has increased expression.

What's important though is knowing that most of the 5HT system facilitates dopamine release. It is an inhibitory neurotransmitter but only for 5HT2C, from what i've read.

A good combination might be a moderate dose of Prozac, since it has a level of 5HT2C antagonism. Adding bupropion would probably resolve the loss of DAT expression.
I still think SSRIs are useful for activating various 5HT receptors to increase dopamine release.

Check this paper out
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562467/

[Halan]

Ok, since I see we are reviving this idea I will share a glimpse of what i think. First of, I don't want to be a smartass since we all are in the same boat but...
Basically, i thought that main problem is dopaminergic pathway mediated not only by 5-HT1A but by 5-HT2A, HT-2C, 5HT-4, 5-HT6, and 5-HT7. It goes from VTA to the limbic and cortic pathways mediated by many receptors.
See this: https://en.wikipedia.org/wiki/Serotonin#Receptors
5-HT6 98.41 Cognition (antagonists ↑); antidepressant effects (agonists & antagonists ↑); anxiogenic effects (antagonists ↑[25]). Gs signalling via activating adenylyl cyclase.
5-HT7 8.11 Cognition (antagonists ↑); antidepressant effects (antagonists ↑). Acts by Gs signalling via activating adenylyl cyclase.

5-HT4, 5-HT6 amd HT7 are upregulated INDIRECTLY, and they ALL affect monoamines, so there's another thing going. And I think it's linked to the phenomenon called Hormesis. I tested it with methylphenidate and it works - taking 50mg in the span of few hours and two 1mg doses stimulated me excessively for 3 days - bad idea if you ask me. However, here's the BEST part: SSRI's from ALL sources that i know, are LOWERING serotonin, not raising. And they lower it by 80-90%. And guess what ? Some article mentioned 5-HT2C in the first 3 weeks upregulated by 90%. Concidence ? I think not. Now, with methylphenidate, taking 1 mg probably lowered my dopamine levels which temporarily upregulated receptors. So, when you are on SSRI, you have lowered serotonin AND up-regulated receptors - brain has homeostasis. However, when you abruptly quit the medication, your serotonin levels are backing up to normal with oversensitized receptors. Many people have symptoms of overactivity of certain serotonin receptors when quiting -
nausesa and loss of apettite -> 5-HT2C,
muscle pain, nausea again - 5-HT3 ? from wiki
CNS: nausea and vomiting center in brain stem, anxiety,[24] seizure propensity [25]
PNS: neuronal excitation (in autonomic, nociceptive neurons), emesis[24]
headache at frontal lobe - 5HT-6 and 5-HT7 ? LSD and associated psychedelics are known for curing migranes, headaches and guess what ? Always when i took acid and it worked (that is, low level ssri in blood while taking it), it alleviated headache AND i had full emotions and usually (but not always) libido was back. So THIS is way i came vack to the medication - acid was the first thing i tried but it DID NOT cure me and i don't recommend taking this because for me it was hit or miss - more of a hit but i don't know whether it could fuck you up. However, it gave hope as i said, since there was nothing damaged.
Some, my 2 cents. Right now I have literally no anxiety (i took ssri for that), i can laugh, have virtually zero brain fog, sexual functions SEEMS to be well stabilizing, have occasional zaps. As is said, i will report changes
All the best

Thanks for this response, Skorpio
You said before something about hitting right dose at right time. How do you take escitalopram? Are you taking other meds/supplements? Did you start with low doses?
I'm thinking about starting sertraline or fluoxetine. Sertraline also inhibits DAT

@Coraggio
That's good news! I didn't know about this study. When he's gonna start it?

@Jaiho
What do you think about sertraline? I'm kind undecided about which drug I'm gonna use, sertraline or fluoxetine

[Skorpio]

First of, try to take what you took before - mechanism of action can differ, even when it comes to citalopram vs escitalopram. See this https://ibb.co/g9CJu5
Basically, for me, it is NOT about lowe dose - it's about the dose around which brain can reapir itself. Gixxer took 37,5 of Venla and gueess what - he felt amazing. And then, he woke up and 10 am to 12 am feeling that this feeling dissapeared. In my opinion, his brain succesfully reinstated ssri and he should took another dose. Now, i'm not saying that this is his fault since I know how all of you feel.
2 things that I monitored day to day, hour by hour, minute-by-fucking-minute:
Set point - the dose at which brain works and start to hit waves, zaps etc.
Pharmacokinetics of given ssri, and it's active metabolite, if present
I took for example 1,25 mg esci, and beetwen 2 and 6 hours felt like shit, BEFORE and AFTER ok. So now take this: escitalopram have maximum concentration at about 3 hours mark. So, basically, if the sweet spot was at 1 mg, this explain why i felt like shit at 3 hours mark - you have to visualize that curve - at this time, the dose was to high, but once, the dose dropped, i felt ok again.
Now, there's another thing - i COULDN'T stabilize at one dose per day. I had to take multiple doses. And that fucking set opints where constantly changing - I could take multiple 1,25 a day, now woke up, and realized that i have to take 7,5, another day total of 2,5mg, another 20mg, another 50 mg - i'm not kidding! I have to take up to 40-45 mg o esci, cause if I didn't i had horrible headache. So then i started to take up to 5,5g OMEGA 3 (with vitamin E included), and could reduce. But, i took it and took it, and took it, for 2,5 months, so at some point i said "i'm jumping off". Last two dodes were: 5 mg, 5 mg and then 10mg at nights, but didn't have any zaps, or patterns, so next day i didn't take any. Today is day 6, have occasional zaps, have some waves, occasional headache, but most of the time feel amazing. Methylphenidate started to work.
One thing - it's not only about sexual function - i didn't realize how i was brainfogged and emotionally impaired until now.
And one LAST thing - I have ADHD and done in total 66 neurofeedback sessions, which includes about 15 HEG - HEG is VERY powerful for relieving anxiety and for overall well being. Now it seems that my brain has ingrained NF sessions and is constantly repairing itself - I have some weird feelings like someone mount screws in my brain, that happened when i started NF sessions Brain is amazing, and REALLY can recover itself. But you have to know what to do
Ok, this is enough for now. I will report as said, buy i'm so exhausted by the past 2,5 months, so I will not respond to every message - i want to chill for few weeks right now, from time to time i will discuss how it goes

Edit - i Started with 0,5 mg at night and tried to stabilize per SA forum, but couldnt. As for supplements - mostly ZMA , magnessium zinc and B6, and started with low amount of OMEGA 3 (550 to 1100mg per day). Omega seems to reduce zaps. That's all. Now i take sometimes speed and MPH since i think how well stimulants works shows how well brain function - weird, i know but few undestand ADDer

[jaiho]

@Jaiho
What do you think about sertraline? I'm kind undecided about which drug I'm gonna use, sertraline or fluoxetine

'

Sertraline was useless for me on its own. worked for about a month with nort.
I'd say fluoxetine since it has actions on 5ht2c.

[theloneranger86]

continuing...

ssri affect allopregnanolone production https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23979/
We don't know how, but maybe in some people SSRI are causing a disruption in this mechanism even after quitting it. Well, I guessed in my last post that maybe we're lacking allopregnenolone, but this is just a guess. Maybe it's too little, or too much allo...
So, going back to ssri and taking it correctly could help... I also suggest don't letting your brain without the medication (if you're taking it). Once you're taking ssri, u should wean off SLOWLY. btw, a ssri that has a long half-life would be the best (like fluoxetine), and taking it more than 1 time in the day makes sense, as Skorpio reported. My low libido didn't started after I quit SSRI, I can't remember exactly when it started, but I started to feel this after a few months in the medication. I must say I was taking fluvoxamine and it has a short half life.

This syndrome is probably connected to PFS sufferers, cause 5α-reductase mediates allopregnanolone synthesis. As we know, Proscar strongly inhibits 5α-reductase.

Yes, in fact we have already noted this connection with PFS. Melcangi is going to study brain neurosteroid levels in brain PSSD rats. And also serotonin and dopamine levels. Now I am trying to convince him to study also the gaba A receptor subunits.
PTSD, a persistant psychiatric syndrome with longlasting effects, shares with pssd one thing: allopregnenolone withdrawal/tolerance. Acute/prolonged extreme fear induces an allopregnanolone spike and this is shared by SSRI action too. Both Cronic allopregnanolone both acute sudden allopragnone withdrawal downregulates alpha4receptor subunit in gaba A receptors. I think that a prolonged SSRI treatment or an acute SSRI cold turkey withrawal can create this huge SHIFT in subunit receptor conpositions so this can lead to a different receptor affinity in many areas and so to a different brain networks.

Gaba A receptor are massively importantvin many different brain areas because Gaba has 33% of all brain synapses and gaba A is the most prevalent gaba receptor.

its been a while since we've been hearing about Melcangi and his experiments, I doubt anything ever came out of it.

[fred1234]

I wanted to post a little update after my trial with Venlafaxine. I upped the dose till half of 37,5. It made me very horny at the beginning but then the effect started to fade away. I stopped it without many problems and now it seems like pssd is not a problem anymore. I live in a nice relationship with a very satisfying sexuality. I wake up with morning erections every morning, have sexual thoughts, kind of everything is almost as it was before I started sertraline when I was 25. Now I am 33 so a little bit less lust might be normal due to the age. So for me the experiment was a success. Good luck to you!

[gianno121]

I wanted to post a little update after my trial with Venlafaxine. I upped the dose till half of 37,5. It made me very horny at the beginning but then the effect started to fade away. I stopped it without many problems and now it seems like pssd is not a problem anymore. I live in a nice relationship with a very satisfying sexuality. I wake up with morning erections every morning, have sexual thoughts, kind of everything is almost as it was before I started sertraline when I was 25. Now I am 33 so a little bit less lust might be normal due to the age. So for me the experiment was a success. Good luck to you!

Thanks for sharing! That sunds promising. For me low dose doesnt cure anything but maybe i should take a higher dose. But a few questions:

1. Do you still take venlafaxin now?
2. how much time did you take it again until pssd was getting better?
3. did you or do you experience penile atrophy (permanent penis shrinkage) or soft glans?

Thanks for sharing your experiences! Best greets

[gianno121]

I wanted to post a little update after my trial with Venlafaxine. I upped the dose till half of 37,5. It made me very horny at the beginning but then the effect started to fade away. I stopped it without many problems and now it seems like pssd is not a problem anymore. I live in a nice relationship with a very satisfying sexuality. I wake up with morning erections every morning, have sexual thoughts, kind of everything is almost as it was before I started sertraline when I was 25. Now I am 33 so a little bit less lust might be normal due to the age. So for me the experiment was a success. Good luck to you!

Thanks for sharing! That sunds promising. For me low dose doesnt cure anything but maybe i should take a higher dose. But a few questions:

1. Do you still take venlafaxin now?
2. how much time did you take it again until pssd was getting better?
3. did you or do you experience penile atrophy (permanent penis shrinkage) or soft glans?

Thanks for sharing your experiences! Best greets

Any new infos?