Why taper? SERT transporter occupancy studies show importance of gradual change in plasma concentration

September 22, 2017

I think I'm just about the only one that I know of for an almost perfect taper. The only variations I did were an extra two weeks when I had bronchitics at around 18mg and an extra 6 weeks at 10mg just to let things settle out. Once I got below .75mg it was tricky to maintain 10% because of the scales, but I kept it as close as possible. That lasted for about 6 drops. Then again by necessity the last couple of drops were 25% and 50% because of limitations of the scales and eyeball method. From everything I've seen I was very lucky to have such a smooth and trouble free taper.

September 22, 2017

ChessieCat,

I downloaded the perfect taper graph you posted. I am using it to compare against mine. I did notice that the graph looked very similar to the dose occupancy curve. Mine of course doesn't look anything like this, but it is something to strive for.

Brassmonkey, I don't know if you have a graph or even care to share it, however if you decide to share I would love to see yours.

RS

September 22, 2017

34 minutes ago, brassmonkey said:

I think I'm just about the only one that I know of for an almost perfect taper.

Well done. I hope you are proud of yourself, it's a big achievement.

1 minute ago, RachelSusan said:

Brassmonkey, I don't know if you have a graph or even care to share it, however if you decide to share I would love to see yours.

I was about to say something similar

September 22, 2017

I have several pages of hand written data, but I never followed up on creating a graph with it. Also doing the slide method makes for a lot of data points. Maybe one of these days.

September 22, 2017

10 minutes ago, brassmonkey said:

Maybe one of these days.

I image you have got lots of much more exciting things to be doing! And nobody can blame you for that.

October 28, 2017

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.

October 28, 2017

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.

November 2, 2017

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.

November 2, 2017

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

November 3, 2017

Will do thanks!

November 3, 2017

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.

November 3, 2017

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.

November 3, 2017

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.

December 29, 2017

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.

December 30, 2017

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.

December 31, 2017

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

December 31, 2017

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.

January 3, 2018

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.

January 6, 2018

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.

January 6, 2018

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))

February 12, 2018

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.

February 13, 2018

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.

February 14, 2018

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.

March 7, 2018

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

sorry, I am a newb on here!

March 7, 2018

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.

March 8, 2018

Merged related topics.

November 4, 2018

I came across this paper, Serotonin Transporter Occupancy of Five SSRIs at Different Doses, that shows a very non-linear relationship between SSRI dose and serotonin transporter occupancy (the alleged "therapeutic" effect). Graphs are shown for citalopram, fluoxetine, sertraline, paroxetine and venlafaxine.

This shows that ADs are often prescribed at far higher doses than necessary, and may also suggest that when tapering from a large dose, you could make relatively large reductions at first, then slow down as you approach the "knee" point on the graph. (note that the sample sizes are small and there is still a large variance between multiple people at the same dose, so ymmv).

Thought this might be useful information for this section of the forum.

November 4, 2018

Please see this topic from the beginning.

November 5, 2018

Ah. Could've guessed this was already posted here. It's good to keep all relevant information in one place.

November 5, 2018

4 hours ago, panic27 said:

This shows that ADs are often prescribed at far higher doses than necessary, and may also suggest that when tapering from a large dose, you could make relatively large reductions at first

I was fortunate in being able to reduce my Pristiq dose from 100mg to 75mg fairly easily (after 3 weeks of extreme cog fog after I tried to go from 100mg to 50mg and thankfully found SA). However when I got to 50mg I held for 3 months and again at 20mg for 7 weeks just to give my brain a chance to catch up if it needed it.

December 16, 2018

Hi All

I found this journal article about Desvenlafaxine (Pristiq). I will try to obtain the full text article.

An open-label positron emission tomography study to evaluate serotonin transporter occupancy following escalating dosing regimens of (R)-(-)-O-desmethylvenlafaxine and racemic O-desmethylvenlafaxine.

Frankle WG, et al. Synapse. 2018.

Show full citation

Abstract

SEP-227162 [R(-)-O-desmethylvenlafaxine] is an enantiomer of the venlafaxine metabolite O-desmethylvenlafaxine (ODV, Pristiq™, Wyeth). This study compared the serotonin transporter (SERT) occupancy achieved by SEP-227162 and ODV, at daily doses of 25, 50, 100, and 150 mg using [11 C]DASB positron emission tomography (PET). Sixteen healthy male subjects participated in one of four dose groups (N = 4 per group) during which they were administered two doses of the study drug (SEP-227162 or ODV). For each study drug, total daily doses of 25, 50, 100, and150 mg were studied. Subjects underwent three PET scans with [11 C]DASB. A baseline, off-medication, scan was performed prior to dosing and a [11 C]DASB PET scan was performed after 72 hr at each dose level. [11 C]DASB binding potential (BPND ) was calculated using the simplified reference tissue method. SERT occupancy was calculated as the change in BPND (ΔBPND ) from baseline scan to the on-medication scan relative to the baseline BPND value. SEP-227162 and ODV significantly reduced regional distribution volumes and region BPND values in a dose-dependent manner. Across all doses ODV produced significantly greater SERT occupancy than SEP-227162 (ANOVA F = 21.8, df = 1,23, p < .001). The total daily dose required to provide 50% SERT occupancy was 24.8 mg for SEP-227162 and 14.4 mg for ODV. In vitro data suggests a ratio of 3.3:1 for binding at human SERT for SEP-227162 relative to ODV. Our study suggests a ratio of 1.7:1, highlighting the value of in vivo imaging in the drug development process.

PMID

29216407 [Indexed for MEDLINE]

Edited December 16, 2018 by ChessieCat
reduced font

December 17, 2018

On 8/29/2014 at 12:26 PM, Barbarannamated said:

Because i have an underactive SERT gene, I was interested in how that plays in and found this in one of the citations:

Effects of Chronic Antidepressant Treatments on Serotonin Transporter Function, Density, and mRNA Level

http://m.jneurosci.org/content/19/23/10494.short

Excerpt from abstract:

"Based on these results, it appears that the SERT is downregulated by chronic administration of SSRIs but not other types of antidepressants; furthermore, the downregulation is not caused by decreases in SERT gene expression."

I hope this is not deviating too far from main topic. I believe it may be a part of why some of us who have been on these drugs for many years experience poopout and/or greater difficulty in discontinuation.

Because i have an underactive SERT gene,

Could you explain this to me ...how you know... what does it mean ...how has it affected your drug use and withdrawal? Bit offtopic I know if you would like to post in on my page or any other place and link to it here that would be find with me... thanks. B

February 4, 2019

I would like to offer up the below research article in light of the fact I am very certain when Glo was decreased in dose of her risperidone from 1.0 mg to .06 mg, changes occurred relating to smooth muscles (autonomic nervous system (ANS)). Gloria has had fairly regular periods for the last 9 months (23 to 25 day cycle) when we dropped to .06 her period was late and she did not start until day 33. Additionally, she had difficulty knowing she had to urinate or have a bowel movement. I had to take her to the bathroom several times in an attempt to get her to urinate, even though she had slept all night or it had been many hours since she had last gone. Gloria knows when she has to use the restroom and can and does get herself there. This is the first time i have ever witnessed this phenomenon in her. I imagine it is due to the fact that her lower dose is 'hitting different receptors' in her brain.

Below they state larger doses of risperidone decrease activity of ANS......but they don't know for sure as the subjects were on multiple meds. In Gloria's case, the ANS was impacted by a much lower dose. Scary thing is smooth muscle (ANS) also regulates the heart activity.....dear goodness....these drugs are poison.

From the Discussion and Conclusion Section of the below article

Quote

In contrast, a few studies state that medication affects ANS activity in patients with schizophrenia. Studies have reported that some antipsychotic drugs, such as clozapine, with wide-ranging receptor affinity profiles, show imbalance between sympathetic and parasympathetic nerve activity [18,19] and that other antipsychotics drugs, such as haloperidol, which are relatively free of significant effects on neurotransmitter receptors except dopamine receptors, have no significant effect on ANS activity [19,38]. The results of those studies suggest that the effects of antipsychotic drugs on ANS function are derived from anticholinergic and antiadrenergic activity. In the present study, levomepromazine and chlorpromazine, which have potent anticholinergic and antiadrenergic effects, were commonly used, and many of our subjects were treated with multiple antipsychotic drugs.

Considering the results of previous studies and receptor affinity profiles, it is a consensus view that antipsychotic drugs have more or less of an effect on ANS activity. However, there is little evidence to indicate the dosage of antipsychotic drugs necessary to affect ANS activity. We investigated the dose-dependent effect of antipsychotic drugs on ANS activity. Our results suggest the following. If the daily dose of antipsychotic drugs is ≤500 mg/day, ANS activity in patients with schizophrenia is not significantly lower than that in controls. If the daily dose of antipsychotic drugs is 501 to 1000 mg/day, antipsychotic drugs exert a large effect on ANS activity and decrease ANS activity. If the daily dose of antipsychotic drugs is ≥1001 mg/day, antipsychotic drugs exert a very large effect on ANS activity and decrease ANS activity significantly. In short, the effect might be large if the dose of antipsychotic drug is high. There was a statistically significant difference in mean GAF scores among three subgroups. However, the result of the multiple regression analysis showed that there was no association between the spectral components of HRV and GAF score after adjustment for variables such as age, sex, BMI, duration of illness, CPZeq, BPDeq, and DZPeq (Table (Table33).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534356/

February 18, 2019

On 3/28/2014 at 12:20 AM, dcrmt said:

If you find a paper, please post the both the name of the medication and a link to the paper

Risperdal (risperidone)

atypical antipsychotic

June 1999

See top p. 873 in the PDF attached

(found at https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.156.6.869)

Risperidone occupancy dose plasma level charts.pdf

February 18, 2019

I apologize for not reading this entire thread, but I wanted to share an image that gives a pie chart for each antipsychotic drug illustrating its preference for various neurotransmitters.

“Possible Dose-Side Effect Relationship of Antipsychotic Drugs: Relevance to Cognitive Function in Schizophrenia”

Medscape

https://www.medscape.com/viewarticle/584586_1

Login required.

"Pie charts of receptor affinity of antipsychotic drugs. Affinity ratios for various neurotransmitter receptors are shown..."

February 18, 2019

That link goes to a log in page. I am not able to view the pie chart.

Why taper? SERT transporter occupancy studies show importance of gradual change in plasma concentration

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