5 minutes ago, Alfred1977 said:

How often do you take Paroxetine per day? Paroxetine inhibits its own metabolism, so it gets more unstable on lower doses (but I guess you know that).

I do know..such a fun drug. I just take it once a day. Honestly I have thought about dosing twice a day but right now I am trying to keep it simple. I struggle with sleep as it is and when I started this drug, I took it in the evening and couldn't sleep so that could be a problem.

I am just holding for now. It's an even slower process for some of us. ❤️🙏

1 minute ago, LostinCanada said:

I do know..such a fun drug. I just take it once a day. Honestly I have thought about dosing twice a day but right now I am trying to keep it simple. I struggle with sleep as it is and when I started this drug, I took it in the evening and couldn't sleep so that could be a problem.

I am just holding for now. It's an even slower process for some of us. ❤️🙏

❤️🙏

 

Hurray, I can do your emojis again 🙂

Wow, you are very informed , @Alfred1977, is there anything specific I should know about Lexapro?

14 minutes ago, Nemina said:

Wow, you are very informed , @Alfred1977, is there anything specific I should know about Lexapro?

Hey @Nemina,

that's nice 🙂, but I am still learning...
Every drug is dangerous and I don't want to be disrespectful to anyone's suffering, but I heard that SSRIs are in general pretty bad. When it comes to dependence and withdrawal they are supposed to be on par with benzos and basically the worst. On the other hand there are other psychotropic drugs that are supposed to be much worse when it comes to other adverse effects. I think Lexapro and Sertraline are probably some of the better SSRIs and Venalfaxine and Paroxetine some of the worse. But in the end they are all bad 🙁
Escitalopram is pharmakinetically pretty stable with a halflife of 30h (I think) and is supposed to be relatively "clean" in the sense that it doesn't mess too much with other neurotransmitters than Serotonin. Its most common API is Escitalopramoxalat, which is supposed to be soluble in water. I somewhere read about 20mg/ml. With respect to adverse reaction it seems to be ok for a SSRI...so that's all positive...the negative thing is that you can get devastated by dependence and can get cns injury when withdrawing or jumping around doses...🤷‍♂️

Thank you @Alfred1977. Someone said, that is especially difficult on the lowest doses. Do you know why that could be?.

8 hours ago, Nemina said:

Thank you @Alfred1977. Someone said, that is especially difficult on the lowest doses. Do you know why that could be?.

Hi @Nemina

you are on a pretty low dose and have come a long way...are you struggling at the moment?

On 2/7/2026 at 2:24 PM, Alfred1977 said:

SERT occupancy going up and down by 10% on a daily basis

Hi, @Alfred1977

 

Where are you getting this info that SERT occupancy for Venlafaxine goes up and down by 10% daily? Can you link a source? I’m wondering if you might be confusing a couple of things.

Edited February 11Feb 11 by FIndRest

16 hours ago, LostinCanada said:

Cold turkey of it to bridge with another unknown to me is more dangerous. 

I think is very important and valid advice IMO!

 

16 hours ago, LostinCanada said:

I know being a mathematician, makes you want to believe you can find some logic to this Insanity but there really isn't any.

100%.

 

It's ok to try to understand this madness but really there is no way make this logical.

 

For those of us injured and off the drug we need to buy ourselves time to heal, which we will.

 

For those injured and still tapering its a more complex game of dodging symptoms and further harm whilst tapering carefully off.

 

I think its so natural to try to find reason and logic and cure in all this but really we can end up ,if we are not careful, getting in the way of what our bodies are good at. Healing.

 

Acceptance and distraction are the keys as far as I am concerned to making through this journey. 🙂 

15 hours ago, Alfred1977 said:

But in the end they are all bad 🙁

I think this statement is very true. Ive heard of this idea that one drug is less bad than the other, but seeing the incredible harm these 'lesser' bad drugs have caused I'm not sure there is much validity to the argument personally. They are all bad. Switching IMO causes more harm as LIC said. How is CTing one drug and then starting another at a high dose supposed to help an already sensitive nervous system! It goes against all the logic we work with currently. 

 

We see many people come to sites like this harmed from these kinds of doctor sanctioned drug switches and dose shifts.

It a shame they have to start their healing process from this state.

 

You are in the strong place with all the knowledge of hindsight, I would take advantage of this for sure my friend! 🙂 

 

12 hours ago, Nemina said:

Someone said, that is especially difficult on the lowest doses. Do you know why that could be?.

This is due to its sert occupancy curve. All ADs respond hyperbolically but some have a steeper drop off than others and Lexapro is particularly steep, so low doses have a larger 'effect on the brain', more so than other drugs.

4 hours ago, FIndRest said:

Hi, @Alfred1977

 

Where are you getting this info that SERT occupancy for Venlafaxine goes up and down by 10% daily? Can you link a source? I’m wondering if you might be confusing a couple of things.

 

Hi @FIndRest,

 

I think we talked about this before. The Hill equation is widely used to model the relation between plasma concentration and receptor occupancy. There are PET scan studies supporting this model and as far as I know everybody does this...also withrawal informed scientists like Sorenson et al. So when plasma concentrations change, ultimately receptor occupancy will change as well. The question that can be asked is "How fast does receptor occupancy adjust to plasma concentrations?". As far as I know there are no studies that deal directly with Venlafaxine with respect to that. But for other SSRIs I think it was shown in PET scans that receptor occupancy changes trail plasma changes by 2-4 hours. Now this will probably depend on the drug and also vary individually but I know that in my case I am reacting very fast to dose changes and this plasma-effect side equilibration can't take much time.

If you want to estimate the daily fluctuations in SERT occupancy, you then for example take a pharmakokinetical bateman decay chain model and calculate. Usually there are three differential equations involved: 1 modelling absorbtion, 1 modelling elimination in the plasma and 1 modelling the equilibration between plasma and effect compartiment. To callibrate the model you need estimates for example for the time of the peak in effect, halflife elimination, absorbtion time, ED50/EC50 etc. There are estimates for those values out there and you can slightly adjust them to better fit your personal experience. In the end you get a curve over 24h in the steady state that gives you the SERT occupancy for each moment in time.
Of course it is only an estimate and I can't tell you for sure whether the difference between the daily peak and trough is 10% or 18%. But in my case this model describes pretty plausible my experience. The last 4 months I was getting brain zaps every early morning in the trough of my 24h curve. Those fluctuations are also very robust. If you start playing with the parameters/input the model keeps showing pretty strong fluctuations. For example, in my last callibration which I found most plausible, the daily difference in SERT occupancy was 17.5% when taking the dose once daily. This dropped down to 4.4% when taking the dose every 12h.

 

P.S.: Another number that suggests that the plasma effectside equilibration does not take very long: A Venlafaxine oder ODV molecule resides only for very few minutes (may maximal 7) on a SERT protein. After that it is released and finds another connection or continues its journey through brain, plasma and the human body.

Edited February 11Feb 11 by Alfred1977

14 hours ago, Alfred1977 said:

Hi @Nemina

you are on a pretty low dose and have come a long way...are you struggling at the moment?

Thank you, Alfred, so kind of you to ask. But I do not want to hijack your thread with my own taping problems. Take care! 

Yes, we’ve talked about this before. I’m not sure I was clear or fully understood you last time, so thanks for sharing more detail.
 

18 hours ago, Alfred1977 said:

The Hill equation is widely used to model the relation between plasma concentration and receptor occupancy. There are PET scan studies supporting this model…

 

Yes — the Hill equation is used to show how drug concentration relates to receptor occupancy, and PET studies support that relationship.

 

But an important point: PET studies typically measure occupancy at a single point in time per person, not hour-by-hour over a day. To my knowledge, there are no PET data showing large daily swings in venlafaxine XR occupancy once the drug has stabilized in the body after repeated doses. The Hill equation doesn’t prove large swings over the course of a day.

 

 

18 hours ago, Alfred1977 said:

But for other SSRIs I think it was shown in PET scans that receptor occupancy changes trail plasma changes by 2-4 hours.

 

All the PET studies showing this were done after a single dose, not after someone had been on a steady dose for days or weeks. There are no PET studies showing hourly or within-day swings in SERT occupancy at steady state.

 

 

18 hours ago, Alfred1977 said:

you can slightly adjust [the parameters] to better fit your personal experience … in my last callibration …

 

This is where it becomes speculative. Once you tweak the numbers to fit symptoms, the model describes what you’re feeling rather than predicting real receptor changes. It can make the math look like there are big swings in occupancy, but that doesn’t mean the receptors are actually fluctuating that much. The model is based on estimates and assumptions, not direct measurements.

 

I know your symptoms are real and you want answers. We all do. I just don’t think such a serious decision (switching ADs) should be based on these models when the data we need isn’t public or simply does not exist.

Personally, I wouldn’t switch ADs. I’ve seen it go wrong too many times in people who’ve experienced destabilization in the past. It’s a big risk — one I am unwilling to take. 

 

Edited February 12Feb 12 by FIndRest

Hi @FIndRest, thank you for posting.

 

Could you please make an introduction thread when you are able to?

Dear @Alfred1977, I am happy you are having such competent discussion partners. I’m really hoping for you that you find a very good decision and make your way out of this terrible situation. It is so hard going through this having to rely on one’s own research and not being able to trust the medical system. Pass gut auf dich auf und alles Gute!
 

Nemina 

7 hours ago, FIndRest said:

To my knowledge, there are no PET data showing large daily swings in venlafaxine XR occupancy once the drug has stabilized in the body after repeated doses.

The problem with Venlafaxine is that it does not stabilize. It is pharmakokinetically unstable and the plasma concentration keeps rising and falling in waves throughout the day...also in the so called "pharmakokinetical steady state" after about 2-3 days of intake.

And there are PET studies that show that SERT occupancy rises FAST (not in particular for Venlafaxine though, as I mentioned.

https://pubmed.ncbi.nlm.nih.gov/16506079/

 

In this study PET scans measured the peak in SERT occ (about 82%) 6h after a single dose of Duloxetine. The time of peak plasma for Duloxetine is also about 6h and the residence time of Duloxetine molecules on SERT is about 70 minutes (7minutes for Venlafaxine)

 

PET scan studies are rather scarce and it is hard to come up with exact numbers in the case of Venlafaxine and other drugs. But the data that exists suggests that Venlafaxine is unstable and the equilibration of plasma and effectside does not take a lot of time in general. There are also bio-chemical arguments that SSRI pass the blood-brain-barrier very fast.

7 hours ago, FIndRest said:

All the PET studies showing this were done after a single dose, not after someone had been on a steady dose for days or weeks

This is not true. In fact there are more PET scan studies where SERT occ gets measured after a couple of weeks of intake. Both kind of studies exist.

 

7 hours ago, FIndRest said:

The model is based on estimates and assumptions, not direct measurements.

Every model is. Direct measurements are expensive and difficult in medicine. Where is th the proof or the measurement supporting your hypothesis that SERT occ levels are stable when taking for example 30mg Venlafaxine once every 24h. Which side of the argument should have the burden of proof, the one claiming stability or the one claiming instability?
 

3 hours ago, Nemina said:

Dear @Alfred1977, I am happy you are having such competent discussion partners. I’m really hoping for you that you find a very good decision and make your way out of this terrible situation. It is so hard going through this having to rely on one’s own research and not being able to trust the medical system. Pass gut auf dich auf und alles Gute!
 

Nemina 

 

Danke, dir auch alles Gute. Du kannst mir übrigens gerne in meinem Thread schreiben wie es dir geht. Ich bin im Moment ein bischen durch den Wind und erschöpft. Wenn ich Zeit finde, schaue ich mir deinen Thread auch mal an. VG

@FIndRest has the lived experience which is why I trust her over some tests that we know aren't always accurate and can be skewed. Also the amount of people involved in the testing is usually very small. 

6 hours ago, Nemina said:

. It is so hard going through this having to rely on one’s own research and not being able to trust the medical system.

Thankfully we have success stories of people just like us, struggling like us with symptoms like us, get off successfully. 

 

It is always your choice @Alfred1977 but though I don't know the studies or the math, every change we make, further kindles our already sensitive CNS.

❤️🙏

On 2/11/2026 at 9:47 AM, Chippy said:

Switching IMO causes more harm as LIC said. How is CTing one drug and then starting another at a high dose supposed to help an already sensitive nervous system! It goes against all the logic we work with currently. 

Hi @Chippy, I don't think it goes against "the logic". I have to choose between two evils...switching causes instability for the CNS and staying causes also instability for the CNS.

1 minute ago, Alfred1977 said:

Hi @Chippy, I don't think it goes against "the logic". I have to choose between two evils...switching causes instability for the CNS and staying causes also instability for the CNS.

@Alfred1977 I totally support you what ever you choose. You are right to educate yourself and make some informed choices which i completely respect. 

1 minute ago, LostinCanada said:

It is always your choice @Alfred1977 but though I don't know the studies or the math, every change we make, further kindles our already sensitive CNS.

❤️🙏

I know, but splitting the dose seems to help. My troughs in the morning are gone and depression and anxiety is less severe. I have no more brain zaps in the morning. The only downside is that I couldnt sleep the first 2 nights and I wake up every night around 1 o clock (my new nightly drug peak). I guess/hope that those issues settle in the next couple of weeks and my system adjusts to the new regime of 2 doses a day.

7 minutes ago, Alfred1977 said:

splitting the dose seems to help

That's good then...better than trying to bridge. 

8 minutes ago, Alfred1977 said:

couldnt sleep the first 2 nights and I wake up every night around 1 o clock

This is what paroxetine at night does to me.

Hopefully it will settle. ❤️🙏

1 hour ago, LostinCanada said:

That's good then...better than trying to bridge. 

Yes, but the instability will increase when tapering and probably peak at a daily dose of around 10mg. Then from 10mg down to 0 instability will decrease. And there is the problem with the dose dumping...

1 minute ago, Alfred1977 said:

the instability will increase when tapering and probably peak at a daily dose of around 10mg. Then from 10mg down to 0 instability will decrease. And there is the problem with the dose dumping

Don't get ahead of yourself....take the wins as they come....you might not have any issues...one day at a time...stay in the present. ❤️🙏

1 hour ago, LostinCanada said:

This is what paroxetine at night does to me.

Hopefully it will settle. ❤️🙏

Yes, thanks, If I succeed, maybe you can also split your dose slowly and gradually like this: 1st dose 8 o'clock am, 2nd dose 9 o'clock am...1st dose 8 o'clock am, 2nd dose 10 o'clock am... and so on until 1st dose 8 o'clock am, 2nd dose 8 o'clock pm?

6 hours ago, Alfred1977 said:

14 hours ago, FIndRest said:

All the PET studies showing this were done after a single dose, not after someone had been on a steady dose for days or weeks

This is not true. In fact there are more PET scan studies where SERT occ gets measured after a couple of weeks of intake. Both kind of studies exist.

You’re right — I worded that wrong. My point was that the PET studies measured occupancy after a single dose, not across a full 24-hour dosing interval at steady state.

 

Personally, I’d be hesitant to make such a big decision relying on models built around assumptions.

Edited February 12Feb 12 by FIndRest