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Phenom

Tapering according to the serotonin transporter occupancy curve

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Phenom

I was browsing through this forum (still new here) and came across an extremely interesting scientific explanation of why the 10% taper is necessary. The following link graphically shows the relationship between Serotonin Transporter occupancy and dosage of two different antidepressants.

 

http://www.mediafire.com/view/f3h1ao5ijfj93/papers#0yp2c8pbjrziaab

 

Now this shows that obviously the relationship between mg drops and percentage occupancy is far from linear, and this is why dropping by a set amount each time results in dramatically different reactions at higher doses vs lower doses.

 

To drive this point home, the graph shows that in terms of 5-HTT occupancy, dropping from 30mg to 10mg is equivalent to dropping from 10mg to 5.5mg which is also equivalent to dropping from 5mg to 3.3mg.

 

Crazy Right? This is why the dynamic 10% Tapering method is so much more effective than cutting an absolute number of mg every time.

 

So being an engineer/math nerd I decided to fit the curve on the graph and solve for the variables, that way I could plug the values into a spreadsheet in excel and see what the Occupancy drop was for each 10% taper cut from 40mg down to 0.1mg and what I found was surprising but also aligned with a LOT of the personal stories I've read on here.

 

When I look by occupancy drop for 10% cuts, it gradually increases from 27mg down to 2.66mg, when cutting 10% at a time the period of largest occupancy drops (according to this methodology) is between 4mg and 1.75mg.

 

My theory (call me crazy) is that occupancy of 5-HTT is the best measurable thing we can correlate to severity of withdrawal. I've read tons of stories of people getting stuck in certain areas (even using the 10% taper method) and hitting walls and those areas are predicted by my spreadsheet.

 

For example, according to the occupancy drop metric of measurement, a 10% drop at 3mg is 3x as strong as a 10% drop at 27mg and the area in general between 2-3mg is the nastiest overall using the 10% taper method.

 

So I designed a new tapering plan for myself based not on % of curent dose, but on occupancy drop. This means that I will always be dropping a stable amount of 5-HTT occupancy (closest thing I can measure for serotonin change) with each cut.

 

I'll be starting from 20mg once I'm ready, and the % drops will vary between 10% and 4% until the dose is down to 0.37mg at which point it will increase until the dose is 0, always maintaining the same occupancy drop of 1% every 3 weeks and seeing how my body responds.

 

This method can be applied at any tapering speed depending on the individual. The key is a consistent drop in serotonin levels with each dosage decrease. 

 

I've attached an excel spreadsheet, the first sheet is the occupancy drop method where you can choose the speed of taper just by changing the field in A3. Also, if interested look at the second page of the spreadsheet which highlights the variable 5-HTT drops at different doses using the 10% taper method.

 

Anyway, just an idea and another method of tapering. Everything in this post is a personal thought/opinion and I am not a doctor or anything. The more information the better I figured, so for those interested have a look and they how the numbers work out for you and if they make sense or correlate with your experience.

 

Occupancy-Taper.xlsx

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Altostrata

Hmmm....I wish it was so predictable. There are other variables as well, such as other drugs or even foods that affect metabolization of the drugs.

 

Please let us know how your experiment goes.

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Songbird

This is the same paper dcrmt posted here:  http://survivingantidepressants.org/index.php?/topic/6036-why-taper-paper-demonstrates-importance-of-gradual-change-in-plasma-concentration/

 

There is an interesting discussion there about the "oh-oh" point.  What you can see on the graph is that below 10mg the curve gets extremely steep.  After years of reading people's posts about tapering it seemed to me that some people did well on a straight 10% taper all the way down, whereas others had much more difficulty in certain dose ranges, although the specific dose ranges varied between individuals.  Some ran into trouble around 10mg, others around 5mg, and others below 3mg.  Some actually found it easier once they got through the difficult range.  This "oh-oh" point would seem to explain why my previous taper went okay down to 5mg and then crashed at 4.5mg.  This experience caused me to believe that there was some kind of threshold where the drug went from "working" to "not working", although I hadn't heard it called the "oh-oh" point until seeing this thread recently.

 

Basing a taper plan on % occupancy drops is an interesting concept, and I agree with a lot of what you have said, although I wonder about your assumption that "occupancy of 5-HTT is the best measurable thing we can correlate to severity of withdrawal".  I am not sure that the same occupancy drop has the same effect at different occupancies, e.g. would dropping from 86% to 85% have the same effect as dropping from 50% to 49%.  Is there an "oh-oh" point for receptor occupancy?  I thought I read 80% somewhere but can't remember where or who.

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Ever

I love your table Phenom!    I'm an analyst and I've thought of doing something similar but never got around to it.   Love it to bits - copied it.  :)

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Altostrata

I'm pretty sure the oh-oh point varies from person to person and there are many factors besides receptor occupancy that determine whether a person feels withdrawal symptoms. Receptor occupancy also varies from drug to drug.

 

Withdrawal symptoms are probably dependent not only on receptor occupancy but how the other neurohormonal and hormonal systems adapt to the new signalling pattern. The receptors are sensors feeding data a web of systems that then need to modify their own signalling.

 

The receptor occupancy curve only confirms the need for a taper at a low, steady rate that approximates the curve.

 

For most people, tapering at 10% based on the last dosage is a close enough approximation to the curve; for people who are very sensitive to dosage changes, a 5% taper is probably sufficient. Listening to your body is the key.

 

Phenom's tapering rate is never steeper than 10%, and becomes even more conservative when the receptor occupancy rate dwindles, i.e. when the dosage is very low. This makes sense and can help a lot of people in that last leg.

 

We often suggest microtapers in this last leg, which is more or less like Phenom's method, and this seems to work much of the time.

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ToesInTheSand

Phenom,

Thanks for letting your nerdy side out and making that Excel sheet. When I downloaded it I got a circular reference error. I'm not sure which cell it's referring to. Can you check it out?

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Rhiannon

Totally cool. Can you make it a graph? I know if I knew how to use Excel I probably could. Might be a good exercise for me.

 

In terms of practical application it's still crucial to listen to your body and adjust accordingly. Withdrawal does seem to involve more than just receptor occupancy (see for example discussions of cortisol perturbation and gut manifestations, among many) and probably lots of variation depending on individual history and genes.

 

But I love what you've.done, and I think this kind of thing can be helpful especially for people dealing with their "health care" providers. (Sorry. Couldn't resist the scare quotes. I am just so cynical about the $tate of our modern corporate-run medical-pharmaceutical complex.)

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ZK2015

Hi,

 

I started this topic a while ago

 

and it has been 6 months now since my last dose of Prozac, so I'd like to share the way I used to taper so may be someone out there benefit from it, However I'd like to point out that I'm not a doctor and that this worked for me merely through trial and error, so here we go.

 

As I mentioned in my first topic my first tapering attempt was too fast that I had awful withdrawal symptoms and had to reinstate, and the 10% approach was too slow for me as I was able to make larger drops without much symptoms, I then found the following research paper here on the forums:

It's a paper on the percentage of serotonin transporter occupancy of Prozac (and other SSRIs) in the brain, in other words it basically measures the amount of serotonin receptors in the brain blocked by the medication, at 20mg most SSRIs will block 75%-85% of these receptors.

After going through the paper I found that the percentage for Prozac occupancy follows the following equation:

 

Occupancy% = 86*dose/(1.94+dose)

 

So for example, if you take 20mg Prozac, the approximate occupancy% = 86*20/(1.944+20) = 78%, and so on.

What I did next was finding the maximum percentage I can go down without suffering too much withdrawal symptoms, and with some trial and error I found this percentage to be 8%, meaning if I'm currently at 78% I can go down to 70% without much withdrawal symptoms, any higher and the symptoms are unbearable.

So I prepared a table with 8% drop downs, calculated the dosage for every percentage and stayed on every dosage from 2-4 weeks depending on the symptoms, this worked perfectly for me as I was able to calculate the next dosage that wouldn't cause much symptoms, for example I was able to drop directly from 20mg to 10 mg and from 10mg to 5mg, however as the dosage decreased the drops where slower to maintain the 8% drop, this also allowed me to know when to stop taking the medication completely, for example at 0.5mg I was still at 18% so I had to drop to as low as 0.1mg before stopping completely.

My last dose was on 17/4/2017, I had to make 14 drops over the course of a year, and although I had a couple of hiccups toward the end I was able to get through them by staying a little longer on the dosage and doing lots of exercise.

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ChessieCat

Hi ZK,

 

Thanks for posting about your tapering method.

 

It would be really great if you could post an update in your Intro topic about what symptoms, if any, and their severity since you stopped taking Prozac.

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Krasiyan

I'm guessing the forumala for Paroxetine will not be Occupancy% = 86*dose/(1.94+dose) ? This really puts me to question how I've been probably 80% + occupancy on 40 mg for years and stopped in just one months time. No wonder I'm withdrawing.

 

Even if I start 5 mg it's gonna bring the occupancy back to about 50% in a month. Thats a lot considering it's only 5 mg. And even if I stabilize on 50 % occupancy does stupid pills aren't made to be reduced by 1 mg so good luck stopping it without some kind of professional or something.

 

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Gridley

Check Brassmonkey's thread.  He reduced from 40mg Paxil cutting pills and using a Gemini 20 scale even at very low doses.

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Krasiyan

Will do thanks!

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ZK2015
20 hours ago, Krasiyan said:

I'm guessing the forumala for Paroxetine will not be Occupancy% = 86*dose/(1.94+dose) ? This really puts me to question how I've been probably 80% + occupancy on 40 mg for years and stopped in just one months time. No wonder I'm withdrawing.

 

Even if I start 5 mg it's gonna bring the occupancy back to about 50% in a month. Thats a lot considering it's only 5 mg. And even if I stabilize on 50 % occupancy does stupid pills aren't made to be reduced by 1 mg so good luck stopping it without some kind of professional or something.

 

 

Hi Krasiyan, the equation for Paroxetine will be  Occupancy% = 102*dose/(5.2+dose)

so yes at 5mg you will be at 50% occupancy, however it is really a matter of trial and error you can try different percentages till you find the one that you can tolerate and start calculating your doses based on it.

also as Gridley mentioned you can cut your pills or make liquid from them, personally I found it easier to measure doses from liquid solution.

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ZK2015
On 10/29/2017 at 12:50 AM, ChessieCat said:

Hi ZK,

 

Thanks for posting about your tapering method.

 

It would be really great if you could post an update in your Intro topic about what symptoms, if any, and their severity since you stopped taking Prozac.

 

sorry I can't edit the intro topic for some reason.

 

but anyway, my symptoms were very mild during tapering even negligible sometimes, they were mostly anxiety and depression, however the hardest part was toward the end when I stopped completely that's when I started having strong feelings of anxiety again "still bearable though", that lasted for almost 2 weeks but I guess I was waiting for some withdrawal symptom to reappear that I made myself anxious.

I felt completely back to normal about a couple of months after I stopped, and I haven't had any problems since then.

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bruno2016
57 minutes ago, ZK2015 said:

I felt completely back to normal about a couple of months after I stopped, and I haven't had any problems since then.

wow thats really awesome! Thanks for sharing with others. 

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kesh

If you invert the formula you get

 

Dose = (1.94*Occ)/(86 - Occ)

 

Where Occ is percent receptor occupancy. 

 

This means that you could plug in the occupancy taper you want and get the required dose. 

 

However, I don't think anyone knows what kind of receptor occupancy taper is best.

 

 

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RealMe
On 11/3/2017 at 9:32 AM, ZK2015 said:

 

sorry I can't edit the intro topic for some reason.

 

but anyway, my symptoms were very mild during tapering even negligible sometimes, they were mostly anxiety and depression, however the hardest part was toward the end when I stopped completely that's when I started having strong feelings of anxiety again "still bearable though", that lasted for almost 2 weeks but I guess I was waiting for some withdrawal symptom to reappear that I made myself anxious.

I felt completely back to normal about a couple of months after I stopped, and I haven't had any problems since then.

Are you still doing well?  I have started a slow taper of prozac 10, so I read your method and got a lot of hope from your experience.

 

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ZK2015
On 12/29/2017 at 11:52 PM, kesh said:

 

However, I don't think anyone knows what kind of receptor occupancy taper is best.

 

 

It's a matter of trial and error really, it took me a couple of tries till I found the highest occupancy I can taper without much problems 

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ZK2015
11 hours ago, RealMe said:

Are you still doing well?  I have started a slow taper of prozac 10, so I read your method and got a lot of hope from your experience.

 

Yes, it's been 8 months now and doing fine, Wish you luck with your taper.

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Altostrata

The fundamental problem is you do not know the exact shape of your own occupancy curve. The paper is based on an average. You cannot assume your own curve is exactly like this one, or that your own tolerance for tapering is dependent solely on receptor occupancy rates.

 

That said, ZK, I'm glad you're doing well. Please update your Intro topic.

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kesh

Yes, one thing about the original papers is how the data points of individuals' sert occupancy float quite widely around the curve.

 

And the 10mg, 20mg, 40mg typical therapeutic doses for say fluoxetine are in reality likely to have a far wider range for different people. 

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DoctorMussyWasHere
On 29/10/2017 at 12:13 AM, ZK2015 said:

Occupancy% = 86*dose/(1.94+dose)

 

Is anyone keeping a central record of the equations?

 

This one is for risperidone:

y = 90*(x/(0.8+x))

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Viridian

So as tapering strategies go, this isn't one SA is likely to endorse any time soon? I'll admit I was excited to see someone had managed to taper from the same drug and dosage as me in just over one year with few lasting ill effects, and was wondering whether I should give this a try for my own taper.

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scallywag
On 1/3/2018 at 4:17 AM, Altostrata said:

The fundamental problem is you do not know the exact shape of your own occupancy curve. The paper is based on an average. You cannot assume your own curve is exactly like this one, or that your own tolerance for tapering is dependent solely on receptor occupancy rates.

Another thing to note is the sample size of the group studied.  The main study linked had sample sizes of 14 and 18; the Cymbalta study had a sample size of 3.  Most scientists will tell you that it is extremely difficult to generalize results for a population of millions based on a single study with a small sample size.

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Altostrata
On 2/13/2018 at 8:48 AM, scallywag said:

Another thing to note is the sample size of the group studied.  The main study linked had sample sizes of 14 and 18; the Cymbalta study had a sample size of 3.  Most scientists will tell you that it is extremely difficult to generalize results for a population of millions based on a single study with a small sample size.

 

Correct, scallywag. These curves only give you the basic idea.

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freedomfrombondage

Does anyone know how I would begin to apply this equation to Lexapro?

 

sorry, I am a newb on here!

 

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Altostrata

The best you can do is approximate it with a 10% taper. See Tips for tapering off Lexapro (escitalopram)

 

Please post questions about your taper in your Introductions topic.

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Altostrata

Merged related topics.

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