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


dcrmt

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carefulprayerful

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Psych drug history goes back, on and off, to 1999.  

Started in 2012/2013:     900 mg  Lithium         3 mg Risperidone               250 mg Lamotrigine

Attempted to taper off in 2014 w/ doctor's guidance and was unsuccessful, except that I was able to reduce risperidone to 1 mg.

2015-2018:                      900 mg  Lithium         1 mg Risperidone                250 mg Lamotrigine

Attempted to taper off again in 2018 and found much better info. about how:

Jan. 2018:                        0 mg  Lithium (CT)     1 mg Risperidone               250 mg Lamotrigine 

Jan. 2019:                        0 mg Lithium               0.625 mg Risperidone       175 mg Lamotrigine

Jan. 2020:                       0 mg Lithium               0.260 mg Risperidone       175 mg Lamotrigine

Feb. 2021:                        0 mg Lithium               0 mg Risperidone              175 mg Lamotrigine

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ADMIN NOTE 17 March 2019 A scientific paper has been published based on the hypothesis put forward in this topic, see    Horowitz, 2019 Tapering of SSRI treatment to mitigate withdrawal symp

yeah like Alto said while I was typing that, only in SO many fewer words. Thanks Alto.    Let me add: my rant is actually directed not just at this thread, but at everyone who says "oh it's the D2 b

This is a great article! While I've known a slow taper is of utmost importance, I now see how particularly critical it becomes at the lower doses. Per the chart, I am now poised to leap from a prever

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You shouldn't post it anyway as it would be copyrighted.

NEW!!!     INTERVIEW with Altostrata, SA's founder    NEW!!! 

 

Plodding along inch by inch:  12" = 1',  3' =  36 " or 1 yard,  1760 yards  = 63,360" or 1 mile

Current from 17 Apr 2021:  Pristiq 0.2665mg  now holding each dose for 3 weeks

ADs since ~1992:  25+ years - 1 unknown, Prozac (muscle weakness), Zoloft; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after); Pristiq:  50mg 2012, 100mg beg 2013 (Serotonin Toxicity)  Tapering Oct 2015 

My tapering program   My Intro (goes to my tapering graph)  My website

PLEASE NOTE:  I am not a medical professional.  I provide information and make suggestions.

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On 11/3/2017 at 8:09 AM, ZK2015 said:

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.

 

This SERT Occupancy graphs makes such a difference in my understanding of why a slow taper is so important. Especially towards the end of the taper.

 

What would be the occupancy equation for Sertraline? 

 

I am giving this taper another go after being on the sidelines for 3 years. Three years ago, I had somewhat manageable withdrawal problems from 50 mg to 37.5 mg to 25 mg to 12.5 mg, but failed miserably when I CT'd at 12.5 mg. I reinstated and held at 12.5 mg for the past 3 years. It looks like 12.5 mg Sertraline is still around 55% occupancy.

 

In Nov 2018, I decided to drop from 12.5 mg to 6.25 mg. I had some withdrawal, but it appeared to be manageable. Held 6.25 mg for 2 months. Then 6.25 mg to 0 mg was a fail. 6.25 mg is still appears to be around 40% SERT occupancy. I have reinstated at 5 mg 1 week ago and waiting to stabilize.

2006-2013: Amitriptyline 25mg QD at bedtime.

Oct 2014: Clonazepam 0.5mg at night for sleep. Gabapentin 600mg x2 daily for pain.

Dec 2014: CT Clonazepam & Gabapentin on doctor’s instruction, because it wasn't helping symptoms. Caused severe depression, anxiety, panic attacks. ER due to 3 days of no sleep. ER administered Lorazepam IV.

Dec 2014: Lorazepam - 0.250mg AM,  0.125mg PM, 0.250mg Beftime; Zoloft - 50mg

Feb 15 - March 11, 2015: Tapered Lorazepam at 0.125 mg ever 5 days. Too fast and very difficult.

June 1 - Oct 12, 2015: Tapered Zoloft from 50mg at 12.5 mg every 4 weeks. Last 2 weeks I took 12.5 mg every other day. Then CT'd at 12.5 mg.

Dec 4, 2015: Reinstated Zoloft 12.5 mg.

Nov 2018: 12.5 mg to 6.25 mg. Held for 2 months then CT'd 6.25 mg on Jan 26.

Feb 16, 2019: Reinstated Zoloft 5 mg

Dec 2019: CT Zoloft 5 mg. Did okay until August 2020.

 

 

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  • 4 weeks later...
On 4/24/2014 at 10:04 PM, Mario said:

nice article !

the shapes of the curves also support the idea that the reduction speed should be reduced at lower dosages of SSRI,

like it is suggested in the turtle protocol (http://ssrigr.altervista.org)

 

Hi, read your history below.

What does the turtle protocol mean? I'm currently at approximately 5,6 ml paroxetine and wondering if i should stop tapering at 5,0 ml.

  • I started using 20 mg Paroxetine (Paxil) in 2004 for stressrelated anxiety
  • I attempted several times to stop using Paroxetine, starting a few years later
  • I found out in 2015 about the withdrawal problems and 5-10% rule
  • I started using liquid Seroxat suspension in 2015/2016
  • From 20 mg to 12 mg, I went down 5-10%
  • From 12 mg down due tot withdrawal I was forced to take smaller steps (0,2 ml/4-6 weeks)
  • 09/2018 at 5,6 ml (11,2 mg) of Seroxat Suspension fluid
  • 11/2018 Switch back to 5,7 ml (11,4 mg) to reinstate
  • Started trying the brassmonkey micro-taper method end dec 2018 (0,03 ml/week)
  • Had to updose to 5,585 3/2019
  • Current dose 5,565 4/2021 after >1 year of withdrawal issues (several food sensitivities and conflicts with painkillers, caffein, chocolate etc.)
  • First goal to reach is 10mg
  • Also interested in bridging/poop out subject. 
  • I'm into sports, animals, business and economics
  • I'm involved in a collective claim against GSK in the Netherlands
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1 hour ago, Sebas said:

 

Hi, read your history below.

What does the turtle protocol mean? I'm currently at approximately 5,6 ml paroxetine and wondering if i should stop tapering at 5,0 ml. 

 

I will respond in your Intro topic.

NEW!!!     INTERVIEW with Altostrata, SA's founder    NEW!!! 

 

Plodding along inch by inch:  12" = 1',  3' =  36 " or 1 yard,  1760 yards  = 63,360" or 1 mile

Current from 17 Apr 2021:  Pristiq 0.2665mg  now holding each dose for 3 weeks

ADs since ~1992:  25+ years - 1 unknown, Prozac (muscle weakness), Zoloft; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after); Pristiq:  50mg 2012, 100mg beg 2013 (Serotonin Toxicity)  Tapering Oct 2015 

My tapering program   My Intro (goes to my tapering graph)  My website

PLEASE NOTE:  I am not a medical professional.  I provide information and make suggestions.

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I've added this simple explanation to Post #1 of this topic:

 

46 minutes ago, brassmonkey said:

 

Most psych drugs work by changing the levels of a specific neurotransmitter in the body. They usually increase the amount of the neurotransmitter by shutting down the receptor that absorbs it. This is called "down regulating" and a receptor that is down regulated is referred to as being "occupied".  These charts show the percentage of receptors in the body that are "occupied"  at a give dosage of the medication.  The percentage is on the left scale and the dose is across the bottom. Both charts are showing the same thing but the one on the left show the affects of the listed strength of the dose while the one on the right shows the affects of how much of the drug ends up in the blood from taking that dose.

 

If you trace a line up from the 10mg mark on the bottom of the left chaft to where it hits the curve and then over to the left it shows that at a 10mg dose 55% of the receptors in the body have been down regulated (shut off).  Do this again for 20mg and you will see that 75% of the receptors have been shut off.  As you can see the higher the dose the more receptors are shut off, but because of the curve of the line the more you take the less affect it has.

 

The curve tells us several things.  For one thing it shows that the larger the dose the less cumulative affect it has, so in reality a very high dose is not much more effective than a lower one.  But more importantly it shows that at the lower doses (10mg and below) a very small change in dose will result in a very large change in occupancy. A large decrease in occupancy means that there is a lot of healing to be done and a large increase in symptoms is most likely.  The curve also shows why it is so important to go slowly at the lower doses as a very small change in dose causes a very large change in occupancy.

 

These charts are one of the bases from which we worked out the 10% taper rule.  The curve line for a 10% taper very closely matches the curve for occupancy.  By removing the occupancy in a controlled manner we can allow the body to heal itself while the drug is still having an affect and keeping WD symptoms at a minimum. It's like playing Jenga and only removing blocks from the top of the stack.

 

 

NEW!!!     INTERVIEW with Altostrata, SA's founder    NEW!!! 

 

Plodding along inch by inch:  12" = 1',  3' =  36 " or 1 yard,  1760 yards  = 63,360" or 1 mile

Current from 17 Apr 2021:  Pristiq 0.2665mg  now holding each dose for 3 weeks

ADs since ~1992:  25+ years - 1 unknown, Prozac (muscle weakness), Zoloft; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after); Pristiq:  50mg 2012, 100mg beg 2013 (Serotonin Toxicity)  Tapering Oct 2015 

My tapering program   My Intro (goes to my tapering graph)  My website

PLEASE NOTE:  I am not a medical professional.  I provide information and make suggestions.

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  • 4 weeks later...
Lakelander82

So if low doses have the vast majority of receptors locked down, why bother tapering at a reduction of 10percent down from 50mg of Sertraline when you could just go straight from 50mg to 12mg in one step and then conduct a 10 percent taper from 12mg to 0.00.

 

 

May 2007 - October 2007 Citalopram 20 mg od. 1st Antidepressant ever taken. No problem with fast taper and no withdrawal effects. No antidepressants for over 5 years.

 

January 2013 started Citalopram 20mg.

March 2014 Switched to Sertraline 50 mg od.

23rd June 2016 started taper 45mg

23.07.16 40.5mg 23.08.16 36.45mg 27.09.16 34.65mg 24.10.16 32.90mg 28.11.16 31.26mg 04.01.17 32mg 25.02.17 31mg 22.03.17 30mg 14.04.17 29mg 09.05.17 28mg 07.06.17 27mg 08.06.17 26mg 13.07.17 25mg 07.08.17 24mg 24.08.17 23mg 13.09.17 22mg 12.10.17 21mg 10.11.17 20mg 04.12.17 19mg 01.01.18 17mg 25.01.18 15mg 22.02.18 13.5mg 25.03.18 12.15mg 

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Lakelander82

Or indeed, if you wanted to be more cautious, went from 50mg to 25mg directly and then conducted a 10percent taper from 25mg because I can’t really see a great deal of difference in the occupancy between 50mg and 25mg. Basically what I’m saying is far too much time spent tapering needlessly at the higher doses when the graphs don’t really back it up. 

May 2007 - October 2007 Citalopram 20 mg od. 1st Antidepressant ever taken. No problem with fast taper and no withdrawal effects. No antidepressants for over 5 years.

 

January 2013 started Citalopram 20mg.

March 2014 Switched to Sertraline 50 mg od.

23rd June 2016 started taper 45mg

23.07.16 40.5mg 23.08.16 36.45mg 27.09.16 34.65mg 24.10.16 32.90mg 28.11.16 31.26mg 04.01.17 32mg 25.02.17 31mg 22.03.17 30mg 14.04.17 29mg 09.05.17 28mg 07.06.17 27mg 08.06.17 26mg 13.07.17 25mg 07.08.17 24mg 24.08.17 23mg 13.09.17 22mg 12.10.17 21mg 10.11.17 20mg 04.12.17 19mg 01.01.18 17mg 25.01.18 15mg 22.02.18 13.5mg 25.03.18 12.15mg 

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Altostrata

It's likely that many people are taking dosages with excess capacity, i.e., they could reduce by 25% and still maintain full SERT saturation, then taper by 10% from there.

 

HOWEVER, we don't know what your individual curve looks like. It could be that a quarter of your dosage saturates your SERT receptors, or it could be that you need 90% for saturation, and a 25% reduction might throw you into acute withdrawal.

 

Admittedly -- we make this clear -- an initial 10% reduction is very cautious. But being that we only offer peer support over the Internet, we can't rescue you should you reduce by 25% and panic because you have severe symptoms. So we advise everyone to go the more cautious route of 10%, where if you do get withdrawal symptoms from tapering, they are less likely to be severe.

 

 

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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  • 2 months later...

@Altostrata, I presume that even though the SERT occupancy chart shows how rapidly things change below the 10mg range, it is only a theory that suggests that there will be an uptick in symptoms below the 10mg range and especially below 5mg?

 

I have read quite a few accounts on here of people having a relatively consistent level of WD intensity throughout their tapers. There may be times where waves are more intense but from what I’ve observed, it seems maybe that there is

alot of variability involved. 

 

Thinking back to @brassmonkey and the

description of his taper, although there were dosages throughout that he described as being a bit more of a hurdle to get past, it didn’t seem to necessarily get more intense the lower he got ? Or have I been interpreting wrong ? 

 

There are also numerous other members who have said that the lower doses have been steady and relatively smooth with a slow taper. Not noticing a worsening in their symptoms.

 

Im certainly not trying to create an argument here , more so im just interested in a discussion as to what other people’s takes are on this.

Do we actually know that the SERT occupancy has a direct correlation with how WD symptoms play out ? 

Started Citalopram in 2005 (aged 15) for apparent "OCD" - 60mg 

July 2015 attempted 2 x 10% + cuts 4 weeks apart. WD symptoms intense at times. Need to slow down.

 

November 2016 - Resumed taper. 1.25 - 1.5% decrease weekly approx.

44.5mg November 2016. Jan 2017 42.5 mg. March 2017 40 mg. June 2017 37mg. September 2018 22mg. Nov 2018 Holding at 22mg to stabilise from moderate wave. January 2020 - Holding, mostly feeling fine, but still having some waves at times. 

 

February 2020 - Resumed taper , 1.5% reduction weekly/every two weeks. 

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12 hours ago, nick1990 said:

Do we actually know that the SERT occupancy has a direct correlation with how WD symptoms play out ? 

@nick1990

For me it has.  The lower I have gone the harder it has gotten.

Find my story here:  http://survivingantidepressants.org/index.php?/topic/12649-rachelsusan-my-zoloft-story-on-off-reinstated-in-trouble/?hl=rachelsusan

HISTORY

Feb. 2016 to June 2016  - Was on 100mg to 150mg Zoloft. 

Quit Zoloft (Sertraline) June  2016,  reinstated 50mg of Zoloft July 2016.  From July 2016  to October 2016 went from 50 mg down 2.3 mg. I up-dosed in November 2016 to 12.5 mg. Held there until January 2017 when I started a much slower taper.

STARTING SENSIBLE  ZOLOFT TAPERING USING GUIDELINES FROM THIS SITE

Dec. 10 2016  - switched to Liquid Zoloft (Sertraline) @ 12.5 mg.   Jan. 4, 2020 1.875 mg (6.3%). Jan. 25, 2020 1.75 mgFeb. 29, 2020 1.625mg (7.10%).  Apr. 4, 2020 1.5 mg. May 9, 2020 1.375 mg. June 6, 2020 1.25 mg. (9.10%). July 4, 2020 1.125 mg. (10%).  August 15, 2020 1.0 mg.  Oct 24, 2020 .875 mg.  Nov. 28, 2020 .75mgJan 16, 2021 .685mg (8.7%).  Feb 13, 2021 .62mg. March 12, 2021 .56mg.

OTHER MEDICATION Gabapentin 900mg a day since July 2016, Prednisone 5mg a day and Qvar Inhalant since 2016. Vitamin D and fish oil.

   

 

 

 

 

 

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13 hours ago, nick1990 said:

 

Do we actually know that the SERT occupancy has a direct correlation with how WD symptoms play out ? 

 

Here's a discussion of the topic you might find of interest.  

 

Why taper paper: dose-occupancy curves

 

One member wrote, "The study was groundbreaking in my opinion in terms of explaining patterns as it seems to corroborate the anecdotal evidence from people here experiencing a shock when they hit the low doses and zero."

 

There are no doubt other factors that play into withdrawal (possibly explaining some members' differing experiences), but to me (no expert) this seems to be a big one.  I definitely had more difficulty once I reached the lower doses, starting around 3.5mg.

 

Gridley Introduction

 

Lexapro 20 mg since 2004.  Begin Brassmonkey Slide Taper Jan. 2017.   

End 2017 year 1 of taper at 9.25mg 

End 2018 year 2 of taper at 4.1mg

End 2019 year 3 of taper at 1.0mg  

Oct. 30, 2020  Jump to zero from 0.025mg.  Current dose: 0.000mg

3 year, 10 month taper is 100% complete.

 

Ativan 1 mg 1986-1991 CT, soon reinstated.  CT 2000. RI 1 mg 2011-2016.  Sept. 2016  0.625mg X 3

Nov.27, 2020, 7-week Ativan-Valium crossover + change to one 18.75mg dose, w/1 month hold.

Feb. 9, 2021, begin 10% every 4 weeks taper.  Current dose as of March 22: 14.4mgai.

 

Imipramine 75 mg daily since 1986.  Jan. 2016 began every 3-weeks 10% taper, down to 16mgai (0.44mgpw).  Aug 2016, discovered SA, holding at 16mg.  Taper is 78% complete.  

  

Supplements: omega, vitamins C, E and D3, magnesium glycinate, probiotic, zinc, melatonin .3mg.


I am not a medical professional and this is not medical advice, but simply information based on my own experience, as well as other members who have survived these drugs.

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  • 4 weeks later...
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, such as

 

2016-July-01, Cymbalta (duloxetine) 

MMarie Found this paper on dose and 5HTT occupancy of duloxetine. Takano, 2005 A dose-finding study of duloxetine based on serotonin transporter occupancy The site,  academia.edu, requires login:

 

Link to screen shot of dose-occupancy and dose-plasma concentration curves

 

2019-October-24, Cymbalta (duloxetine)

Guilietta Found this paper on dose and 5HTT occupancy of duloxetine. Sho Moriguchi, MD, PhD, et al. Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2.

 

The site, Researchgate.net, requires login

 

Scroll to pages 959 and 960 of the article to see the dose-occupancy and dose-plasma concentration curves.

 

Signicance Statement excerpted from the article: "The result showed approximately 30% to 40% NET occupancies in the brain by the administration of 20 to 60mg of duloxetine."

 

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  • 3 months later...
On 2/6/2020 at 8:46 AM, Andie said:

Here is the link to what I found on Desvenlafaxine 

 

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.

 

Current Dose

0.5mcg Clonidine and 1.25 Diazepam PRN for treatment of iatrogenic hypertension. 

2010 .Prescribed Pristiq 100 mg in July by GP

2010 .Reduced to 50mg by splitting and weighing. Held at 50mg

2014. Reduced from 50-35 .Held at 35mg. 

2017. Taper from 35mg commenced using compounded Desvenlafaxine

2018. 23/06 13.5mg. 21/07  12.5mg. 25/08 11.5mg. 09/2018 10mg. 14/11 11mg (updose) 21/11 -12mg (updose)

2019. Still holding at 12mg and stuck. 

2020. January 2019 Prozac Bridge-- Prozac 2.5 to 10mg and

Pristiq 23rd Jan 6mg/ 27th Jan 5mg/ 28th Jan 3mg/ 30 Jan 0

Prozac 6th Feb 9.5mg. Vitamin D3 5000iu with K2

Magnesium Glycinate with Glycine and Passionflower  600mg 

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  • 2 months later...
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On 8/7/2014 at 4:37 PM, btdt said:

 

 exponential decay in tapering is closer to the descending curve

Maybe I am just flat out stupid I don't know but I don't get what your trying to say. 

I thought the graphs showed the amount the body/brain could use had a limit beyond that limit it was a waste of the drug and who knows that the excess does to the body.  

And that tapering is easy at the start because the drug was in excess anyway which was off the graph... so effects were not felt till tapering reached the graph where affects were felt. 

I do worry that maybe others here especially new folks in hard withdrawal will have trouble with this jargon... I could be stupid often think I am.

Yes, I am one of those who are in significant withdrawal, and struggling to understand all of this scientific jargon.  I've been trying to read this thread for over an hour, and am still on page 1.  😕.    

***Please note this is not medical advice.  Discuss any decisions about your medical care with a doctor who understands psych meds and how to withdraw from them, if you can find one.

Lexapro   Started Apr 15 02 - 10 mg;  Apr 2 20  0.18 mg; Jul 16  0.17 mg, Aug 23  0.16 mg, Oct 7  0.15 mg, Nov 8 - 0.14, Jan 16 '21 - 0.13, Feb 7 - 0.12, Feb 22 - 0.11, Mar 26 - 0.10 

Trazodone.  used 50 mg once every 4-7 days for sleep, stopped

Xanax. used 0.5 mg once every 4-7 days for sleep, stopped

Benadryl 50 mg, Ibuprofen 800 mg, or Tylenol 1000 mg

other meds: Levothyroxine 75 mg

suppl AM: fish oil, flax oil, multivitamin, vit C, vit E, calcium

suppl PM: magnesium 350 mg, GABA 750 mg, Estroven, melatonin 3 mg, calcium

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  • 2 months later...
  • Moderator Emeritus

 

BrassMonkey posted this in a member's topic.  I thought it may be helpful including it here in this topic:

 

11 minutes ago, brassmonkey said:

Hi Nivsch-- Chessie sent you a link to what is called the SERT Occupancy chart.  This is the basis for the 10% every four weeks that we recommend as a starting point. By following this hyperbolic curve it is possible to remove the medication at about the same rate that the bodies receptors require to heal.  This keeps WD symptoms to a minimum during that period. If a person reduces too much or to fast there is unfinished healing that builds up in the background.  When that unfinished healing gets to be too much the person "crashes" with an outbreak of acute symptoms. This requires an extended hold period at that dose lever to allow the body to catch up.  

 

If a person goes slower than the recommended taper there is much less of a problem.  To a small extent the body can get ahead of the curve and do some healing before it is needed.  Once a taper has been established, on some cases, the body can anticipate the upcoming changes and get a head start on them. In effect becoming habituated to the idea of tapering and having some momentum in a downward direction. But it is a delicate balancing act to maintain as there are so many different factors involved in a smooth taper.

 

There are differing results for how easy a taper becomes over time. It is  split between the taper becoming easier and it becoming harder.  Because of the SERT Curve we can see that there is a bias toward it becoming harder. As you can see the lower the dose the move affect it has on the SERT loading so a small adjustment can lead to a large change. This is why we recommend people going slower and smaller changes toward the end of a taper. Frequently. if a person had fine tuned their taper, they will feel improvements the lower they go in dose.

 

NEW!!!     INTERVIEW with Altostrata, SA's founder    NEW!!! 

 

Plodding along inch by inch:  12" = 1',  3' =  36 " or 1 yard,  1760 yards  = 63,360" or 1 mile

Current from 17 Apr 2021:  Pristiq 0.2665mg  now holding each dose for 3 weeks

ADs since ~1992:  25+ years - 1 unknown, Prozac (muscle weakness), Zoloft; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after); Pristiq:  50mg 2012, 100mg beg 2013 (Serotonin Toxicity)  Tapering Oct 2015 

My tapering program   My Intro (goes to my tapering graph)  My website

PLEASE NOTE:  I am not a medical professional.  I provide information and make suggestions.

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  • 4 weeks later...

My feeing goes against those occupacy curves.

 

1. Every time I reduce my dose of cymbalta (today in 50.8) by 1% I feel well the reduce after 2-4 days.

The cymbalta occupacy graph says: "Mast be from something else. you changed only 0.05% in serotonin occupaccy".

(screenshot added).

and 0.05% is 1/2000! 

Mutliply by 0.85 (assuming this is the max occupacy) and get 1700.

 

Are you really going to tell me I have to feel this - medium in difficulty - simptom 1700 more times before I fully recover?

 

This graph must be significantly wrong in my case.

 

2. In the past when I tried to reduce venlafaxine from 187.5mg to 150mg I felt very significant anxiety and had to updose back.

The venlafaxine occupacy graph: "you did nothing".

 

How can we explain that?

 

In one side this upsetting when you reduce so little and feel significant change.

But in the other side its also good news, because it says you are NOT in the saturation zone and the reduction holds in it a significant amount of healing points 😮

 

Note that only next week I will know for sure if the reductions in cymbalta cause these feeling and not other things.

 

198187154_duloxetineoccupacy.thumb.png.e7c4af06e4f544c605b4375a07dd49d3.png

 

 

2010-2015 Cipramil 20-40mg. half-year break in the middle which was tough.

2015-2020 Venlafaxine 150-225 mg. Venlafaxine duloxetine cross taper details 

150 for half-year then 225 for a period than stabilized in ~187.5 (1.25 pills) for 2 years than reduced to ~168.5 (1.125 pills).

3.2020 - Duloxetine 60mg.

19.05.2020 - started to taper - 59! 20.5 - 58.5

June 2020: 57. end of June - 55.5

July-August 2020: 5.7 - 54, 9.7 - 52, 12.7 - updose to 53+, 19.7 - 52.3, 26.7 - 51.8, 4.8 51.3, 11.8 - 50.8, 15.8 - updose to 51.0, 17.8 - 50.5, 19.8 - 50.3, 19.9 - 49.3, 7.10 - 46.8, 1.12 - 45.8, 17.2 - 44.4, 30.12 - 42.4, 21.1 - 40.8.

 

17.02.2021 - 40.1 📌 (current dose)

 

 

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After a dose reduction, decline of the drug in your bloodstream is gradual. Because of Cymbalta's half-life, you are feeling the dose reduction when the change fully registers in your bloodstream. For most antidepressants, this takes about 4 days.

 

Your experience matches the expected dose-response curve.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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12 hours ago, Altostrata said:

After a dose reduction, decline of the drug in your bloodstream is gradual. Because of Cymbalta's half-life, you are feeling the dose reduction when the change fully registers in your bloodstream. For most antidepressants, this takes about 4 days.

 

Your experience matches the expected dose-response curve.

 

So the problem here is (probably) cymbalta's short half-life which makes significant symptoms regardless of the occupacy graph?

 

Which means my body doesn't have time to smoothly-adjust no matter how small is the reduction (because of the 12h half life), which makes the gap to always be felt?

2010-2015 Cipramil 20-40mg. half-year break in the middle which was tough.

2015-2020 Venlafaxine 150-225 mg. Venlafaxine duloxetine cross taper details 

150 for half-year then 225 for a period than stabilized in ~187.5 (1.25 pills) for 2 years than reduced to ~168.5 (1.125 pills).

3.2020 - Duloxetine 60mg.

19.05.2020 - started to taper - 59! 20.5 - 58.5

June 2020: 57. end of June - 55.5

July-August 2020: 5.7 - 54, 9.7 - 52, 12.7 - updose to 53+, 19.7 - 52.3, 26.7 - 51.8, 4.8 51.3, 11.8 - 50.8, 15.8 - updose to 51.0, 17.8 - 50.5, 19.8 - 50.3, 19.9 - 49.3, 7.10 - 46.8, 1.12 - 45.8, 17.2 - 44.4, 30.12 - 42.4, 21.1 - 40.8.

 

17.02.2021 - 40.1 📌 (current dose)

 

 

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NEW!!!     INTERVIEW with Altostrata, SA's founder    NEW!!! 

 

Plodding along inch by inch:  12" = 1',  3' =  36 " or 1 yard,  1760 yards  = 63,360" or 1 mile

Current from 17 Apr 2021:  Pristiq 0.2665mg  now holding each dose for 3 weeks

ADs since ~1992:  25+ years - 1 unknown, Prozac (muscle weakness), Zoloft; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after); Pristiq:  50mg 2012, 100mg beg 2013 (Serotonin Toxicity)  Tapering Oct 2015 

My tapering program   My Intro (goes to my tapering graph)  My website

PLEASE NOTE:  I am not a medical professional.  I provide information and make suggestions.

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@ChessieCat

Thanks. It drops so fast. no wonder.

I start to think there is no future to keep tapering this absurd pill.

 

I will give it one more try next week, if it keep be the same i will try 0.5% (~one bead) every 3 days and if IT also won't be good i will do a switch. 0.5% every 4-5 days will be too slow and I dont want to be in 30mg only in october 2021... there is also a limit to how SLOW I can tolerate (not only to how fast)

 

2010-2015 Cipramil 20-40mg. half-year break in the middle which was tough.

2015-2020 Venlafaxine 150-225 mg. Venlafaxine duloxetine cross taper details 

150 for half-year then 225 for a period than stabilized in ~187.5 (1.25 pills) for 2 years than reduced to ~168.5 (1.125 pills).

3.2020 - Duloxetine 60mg.

19.05.2020 - started to taper - 59! 20.5 - 58.5

June 2020: 57. end of June - 55.5

July-August 2020: 5.7 - 54, 9.7 - 52, 12.7 - updose to 53+, 19.7 - 52.3, 26.7 - 51.8, 4.8 51.3, 11.8 - 50.8, 15.8 - updose to 51.0, 17.8 - 50.5, 19.8 - 50.3, 19.9 - 49.3, 7.10 - 46.8, 1.12 - 45.8, 17.2 - 44.4, 30.12 - 42.4, 21.1 - 40.8.

 

17.02.2021 - 40.1 📌 (current dose)

 

 

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5 hours ago, Nivsch said:

 

So the problem here is (probably) cymbalta's short half-life which makes significant symptoms regardless of the occupacy graph?

 

Which means my body doesn't have time to smoothly-adjust no matter how small is the reduction (because of the 12h half life), which makes the gap to always be felt?

 

This is not a problem, it's the way your body reacts to the drug. You maybe a fast metabollzer. You might try a slightly smaller reduction.

 

The occupancy graphs have nothing to do with the half-life of any of the drugs.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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18 minutes ago, data17 said:

A receptor occupancy curve is not the same thing as a dose- response curve.

 

That is correct. If you look at Nivsch's symptom pattern, it matches the decay in dose-response after decrease.

 

Aronson, J. K., & Ferner, R. E. (2016). The law of mass action and the pharmacological concentration–effect curve: Resolving the paradox of apparently non‐dose‐related adverse drug reactions. British Journal of Clinical Pharmacology, 81(1), 56–61. https://doi.org/10.1111/bcp.12706

 

As discussed somewhere above, the SERT occupancy data is only a very rough indicator of overall adaptation of the organism to the action of a drug. (Personally, I consider it to be a metaphor.)

 

Hyman, S. E., & Nestler, E. J. (1996). Initiation and adaptation: A paradigm for understanding psychotropic drug action. American Journal of Psychiatry, 153(2), 151–162. https://doi.org/10.1176/ajp.153.2.151

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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3 hours ago, Altostrata said:

 

As discussed somewhere above, the SERT occupancy data is only a very rough indicator of overall adaptation of the organism to the action of a drug. (Personally, I consider it to be a metaphor.)

 

Hyman, S. E., & Nestler, E. J. (1996). Initiation and adaptation: A paradigm for understanding psychotropic drug action. American Journal of Psychiatry, 153(2), 151–162. https://doi.org/10.1176/ajp.153.2.151

 

What this means is that although the occupacy graph slope is significant only in the first 10-20 mg, still because there are many other factors like cellular changes, genes etc which makes the real pictures much more complicated, it is still possible that reduction from 50mg to 40mg and the reduction from 20 to 10 can still be equally significant in the amount of healing they give (regardless of what the graph says)?

2010-2015 Cipramil 20-40mg. half-year break in the middle which was tough.

2015-2020 Venlafaxine 150-225 mg. Venlafaxine duloxetine cross taper details 

150 for half-year then 225 for a period than stabilized in ~187.5 (1.25 pills) for 2 years than reduced to ~168.5 (1.125 pills).

3.2020 - Duloxetine 60mg.

19.05.2020 - started to taper - 59! 20.5 - 58.5

June 2020: 57. end of June - 55.5

July-August 2020: 5.7 - 54, 9.7 - 52, 12.7 - updose to 53+, 19.7 - 52.3, 26.7 - 51.8, 4.8 51.3, 11.8 - 50.8, 15.8 - updose to 51.0, 17.8 - 50.5, 19.8 - 50.3, 19.9 - 49.3, 7.10 - 46.8, 1.12 - 45.8, 17.2 - 44.4, 30.12 - 42.4, 21.1 - 40.8.

 

17.02.2021 - 40.1 📌 (current dose)

 

 

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4 hours ago, Altostrata said:

The occupancy graphs have nothing to do with the half-life of any of the drugs.

 

Yes I just thought that how can it be that a reduction of only 0.05% in occupacy will be felt at all? Because its so little. So maybe its strenghten the assumption that the occupacy graph is just a very tiny part of the picture.

 

If the occupacy graph was a good indicator, I would suppose to barely feel or feel only weakly a reduction of 0.05% (1/2000) no matter how fast my metabolism, no?

2010-2015 Cipramil 20-40mg. half-year break in the middle which was tough.

2015-2020 Venlafaxine 150-225 mg. Venlafaxine duloxetine cross taper details 

150 for half-year then 225 for a period than stabilized in ~187.5 (1.25 pills) for 2 years than reduced to ~168.5 (1.125 pills).

3.2020 - Duloxetine 60mg.

19.05.2020 - started to taper - 59! 20.5 - 58.5

June 2020: 57. end of June - 55.5

July-August 2020: 5.7 - 54, 9.7 - 52, 12.7 - updose to 53+, 19.7 - 52.3, 26.7 - 51.8, 4.8 51.3, 11.8 - 50.8, 15.8 - updose to 51.0, 17.8 - 50.5, 19.8 - 50.3, 19.9 - 49.3, 7.10 - 46.8, 1.12 - 45.8, 17.2 - 44.4, 30.12 - 42.4, 21.1 - 40.8.

 

17.02.2021 - 40.1 📌 (current dose)

 

 

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4 hours ago, Nivsch said:

If the occupacy graph was a good indicator, I would suppose to barely feel or feel only weakly a reduction of 0.05% (1/2000) no matter how fast my metabolism, no?

 

Probably.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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  • 3 weeks later...
  • Moderator

Escitalopram vs Citalopram serotonin transporter occupancy available in this study, for those who are interested: https://link.springer.com/article/10.1007/s00213-006-0486-0

 

"In vivo imaging of serotonin transporter occupancy by means of SPECT and ADAM in healthy subjects administered different doses of escitalopram or citalopram

 

Background: Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram."

 

Note this diagram is only after a single dosage. Daily dosages would result in greater occupancy of the SERT.

 

SERT occupancy citalopram vs escitalopram diagram.png

Remeron - 2004-2005 (bad withdrawal)

Clonazepam - 2005-2018 (jumped around March)

Olanzapine - 2014- late 2017

Domperidone - 2008-2018

Many drugs in between including Lexapro, other benzos and z-drugs.

Still suffering post-withdrawal from Clonazepam (Klonopin), Olanzapine and Domperidone. 

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  • 2 months later...
On 10/28/2017 at 6:13 PM, ZK2015 said:

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

 

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

Does anyone know what the equation for Effexor xr (Venlafaxine xr), percentage occupancy is?  

1993-2000: Zoloft few months CT, Prozac 1-2 yrs, Ritalin PRN

2002/2003: Wellbutrin,  Paxil 25mg FT, and Xanax PRN CT (all 3 to 6 months), Adderal 40mg, Strattera 40mg

2003- 2016: Effexor XR 75 mg to 150 mg., Strattera (2002-2008)

2017: Effexor XR 225 mg. Gabapentin 300 mg. Elavil 25 mg.

2018: (Sept.) Effexor XR 187.5 mg, Zoloft 10 mg. (OCT.) FT off Gabapentin (NOV.) FT off Elavil (DEC) FT Effexor to 150 mg.

2019: (JAN.) D/C Zoloft, added Viibryd 10mg (FEB) CT Viibryd, (MAR) Prozac bridge, Effexor xr 112.5mg, (Sept.) Effexor XR 112.5 mg + 0.4 mg (1 bead), (Oct.) Effexor XR 112.5mg, (Dec.28) start 10% taper Effexor XR 101.25 mg, 

2020: (Jan. 25) Effexor XR 91 mg., (Feb. 22) Effexor xr 82 mg., (Mar. 21) 75 mg. 

Supplements:  Vitamin D 5000 IU topical, Probiotic 6 billion CFU, Epsom salt bath 1C 2 to 3 X week, California Poppy 2 droppers, various essential oils 

https://www.survivingantidepressants.org/topic/21446-superwoman-effexor-taper/page/8/?tab=comments#comment-475779

 

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  • 4 months later...
  • Mentor
Colonial

From the "Amusing article from a psychiatrist" on page one of this thread:

 

"higher doses aren't more, they are different.(2)"

 

Which is why new symptoms can occur at any point in a taper.

 

 

 Starting ds 2 (12.5 CR'S) = 25 MG PAXIL CR 1/21/15: 1 Pill + 10mg liquid (2 weeks) 2/4: 1 Pill + 9mg Lq (3 weeks) 2/25: 1 Pill + 8 mg lq (1 week) 3/4: 1 Pill + 6 mg lq (2 weeks) 3/18/15 1 Pill + 4 mg lq (2 weeks) 4/1/15 1 Pill + 3 mg lq (2 weeks) 4/14/15 1 Pill + 2 mg lq (2 weeks) 4/29/15 1Pill + 1 mg lq (16 days) 5/15/15 1 12.5 mg Pill ONLY (9 days) 5/24/15 12 mgs liquid (8 days) 6/1/15 11mg lq (12 days) 6/13/15 10 mg.  12/3/15 Drop from 8mg to 7.6 (24 days to) 12/27/15 7.2mgs  8/4/16 6.8mgs,  11/1/16 6.4mgs, 2/5/17 6 mgs  4/3/17 5.6mgs, 4/24/17 5.2mg, 6/13/17 4.8mgs, 9/20/17 4.4mgS, 11/23/17 4 mgs, 1/1/18 3.6 mgs, 2/15/18 3.2 mgs. 4/13/18 2.8mgs, 5/11/18 2.4mgs, 6/10/18 2.0 mgs, 8/4/18 1.6mgs,  9/27/18 1.2mgs, 12/24/18 0.8mg, 3/24/19 0.64 mg,(syringe change issue date?) 4/22/19 0.60 mg, 5/24/19 0.60 mg, 7/7/19 0.52 mgs, 8/4/19 0.44mgs, 11/4/19 0.36mgs, 2/1/20 0.28mgs, 3/1/20 0.24mgs (crash April 6)

 

Original Wellbutrin Dose: 6 months from 9/14 to 3/2015, 300 XL 3/15/15: Half to 150 XL ( severe symptoms started on day 12) 4/16/15: 125mg   for 20 days to: 5/6/15:   100mg  for  15 days to: 5/21/15    75mg  for  10 days to: 6/1/15:  56.25mg      13 days to: 6/13/15: 37.25mg    7 days to: 6/20/15  28.12mg   14 days to: 7/4/15  18.75mg, 7 days to: 7/11/15; RAISE BACK TO: 28.12 to 8/14/15: 18.75mg  20 days to :9/3/15 : 12.5mg, 8/4/16 9mg 1/9/17: 8.5mg 2/8/17 8mg, 3/9/17: 7.6  4/9/17  7.2  5/27/17 6.4 6/24/17 5.8, 8/1/17 5.0, 8/29/17 4.2mgs, 10/2/17 3.5mgs, 12/28/17 2.5mgs, 2/27/18 1.7mgs,  4/19/18 0.8 mgs, LAST DOSE: 6/11/18:  3 YEARS, 2 MONTHS, 27 DAYS...

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