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

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Meimeiquest

BTDT, you are so not stupid. I think it means what you think. As levels get lower, there is a much greater decrease in % of transporters affected for each little amount of drug taken away.


1st round Prozac 1989/90, clear depression symptoms. 2nd round Prozac started 1999 when admitted to dr. I was tired. Prozac pooped out, switch to Cymbalta 3/2006. Diagnosed with bipolar disorder due to mania 6/2006--then I was taken abruptly off Cymbalta and didn't know I had SSRI withdrawal. Lots of meds for my intractable "bipolar" symptoms.

Zyprexa started about 9/06, mostly 5mg. Tapered 4/12 through12/29/12

Wellbutrin. XL 300 mg started 1/07, tapered 1/18/13 through 7/8/13

Oxazepam mostly continuously since 6/06, 30mg since 12/12, tapered 1.17.14 through 8.26.15

11/06 Lithium 600mg twice daily, 2.2.14 400mg TID DIY liquid, 2.12.14 1150mg, 3.2.14 1100mg, 3.18.14 1075mg, 4/14 updose to 1100mg, 6.1.14 900 mg capsules 7.8.14 810mg, 8.17.14 725mg, 8.24.24 700mg...10.22.14 487.5mg, 3.9.15 475mg, 4.1.15 462.5mg 4.21.15 450mg 8.11.15 375mg, 11.28.15 362.5mg, back to 375mg four days later, 3.4.16 updose to 475 (too much going on to risk trouble)

9/4/13 Toprol-XL 25mg daily for sudden hypertension, tapered 11.12.13 through 5.3.14, last 10 days or so switched to atenolol

7.4.14 Started Walsh Protocol

56 years old

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lionboy

I also don't think you are stupid BTDT. I think we all have to be very careful when trying to draw any finite conclusions from a study such as this.

As Alto mentioned earlier in the thread, the findings here do appear to be indicative of the reason people need to slowly taper from these drugs however I would be very careful of drawing any firm conclusions from this.

As I understand it, nobody has proven a relationship between SERT occupancy and the way a person feels furthermore there is no accurate way of measuring seratonin in a living brain ?

This study is done by measuring seratonin in the gut then extrapolating the amount they think that means is in the brain.

In addition, new research suggests that seratonin levels decrease with age so you would therefore expect people to gradually get more depressed the older they get which of course doesn't happen.

The fact is that no one really understands the full mechanics of the effects these drugs have on the human brain.

This type of research will no doubt prove one day to be a part of the jigsaw but I really believe that is all it is, just one part of the jigsaw.


1999 50mg citalopram / celexa for anxiety and depression.

dec 2007 50mg - 40mg, march 2009 40mg - 30mg, july 2009 30mg - 20mg, aug 2009 20mg - 30mg, sept 2009 30mg - 20mg, jan 2010 20mg - 30mg, july 2010 30mg - 25mg (one 20mg and half a 10mg tablet), july 2010 - july 2013 25mg

 

July 2013 began tapering down in 1mg increments, dissolving the tablets in water and using a syringe as suggested by Rhi. Had a few hiccups along the way as can be seen in my thread.

 

End December 2013, now down to 11.25mg.

Dec 2013 to present day still on 11.25 mg. I have hit, what Professor Healy terms, a shelf. I became extremely destabilised when I reduced from 12.25mg to 11.25mg. Only now, after some 15 months am I starting to really recover from it.

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lionboy

* I may be wrong, regarding how they measure SERT !

I started to read into it but lost the will to live.


1999 50mg citalopram / celexa for anxiety and depression.

dec 2007 50mg - 40mg, march 2009 40mg - 30mg, july 2009 30mg - 20mg, aug 2009 20mg - 30mg, sept 2009 30mg - 20mg, jan 2010 20mg - 30mg, july 2010 30mg - 25mg (one 20mg and half a 10mg tablet), july 2010 - july 2013 25mg

 

July 2013 began tapering down in 1mg increments, dissolving the tablets in water and using a syringe as suggested by Rhi. Had a few hiccups along the way as can be seen in my thread.

 

End December 2013, now down to 11.25mg.

Dec 2013 to present day still on 11.25 mg. I have hit, what Professor Healy terms, a shelf. I became extremely destabilised when I reduced from 12.25mg to 11.25mg. Only now, after some 15 months am I starting to really recover from it.

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btdt

Thanks Lionboy I get trying to sort out this sort of thing can cause one to lose the will to live... 

happens to me all the time and I leave it or just forget about it naturally with my forgetful brain. 

That too happens a lot. 

I guess we are just light years behind what we thought we knew as a human race and taking drugs we have no business taking as nobody knows anything really about them  I wonder if it would make any sense to be frozen and defrosted in 3014... when they know how to fix me. If only all I loved would go with me. :) 

thanks again peace to you


WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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Barbarannamated

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.


Pristiq tapered over 8 months ending Spring 2011 after 18 years of polydrugging that began w/Zoloft for fatigue/general malaise (not mood). CURRENT: 1mg Klonopin qhs (SSRI bruxism), 75mg trazodone qhs, various hormonesLitigation for 11 years for Work-related injury, settled 2004. Involuntary medical retirement in 2001 (age 39). 2012 - brain MRI showing diffuse, chronic cerebrovascular damage/demyelination possibly vasculitis/cerebritis. Dx w/autoimmune polyendocrine failure.<p>2013 - Dx w/CNS Sjogren's Lupus (FANA antibodies first appeared in 1997 but missed by doc).

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Rhiannon

Do you think this is the case for gaba and benzodiazepines?

 

This particular paper (which unfortunately the link doesn't work to any more) didn't cover benzos, but experientially, anecdotally, people have always found that the taper with those has to go slower as the doses get lower too. Same kind of thing where you have to cut by a percentage of the current dose not by constant increments. So presumably it's something similar going on.


Started on Prozac and Xanax in 1992 for PTSD after an assault. One drug led to more, the usual story. Got sicker and sicker, but believed I needed the drugs for my "underlying disease". Long story...lost everything. Life savings, home, physical and mental health, relationships, friendships, ability to work, everything. Amitryptiline, Prozac, bupropion, buspirone, flurazepam, diazepam, alprazolam, Paxil, citalopram, lamotrigine, gabapentin...probably more I've forgotten. 

Started multidrug taper in Feb 2010.  Doing a very slow microtaper, down to low doses now and feeling SO much better, getting my old personality and my brain back! Able to work full time, have a full social life, and cope with stress better than ever. Not perfect, but much better. After 23 lost years. Big Pharma has a lot to answer for. And "medicine for profit" is just not a great idea.

 

Feb 15 2010:  300 mg Neurontin  200 Lamictal   10 Celexa      0.65 Xanax   and 5 mg Ambien 

Feb 10 2014:   62 Lamictal    1.1 Celexa         0.135 Xanax    1.8 Valium

Feb 10 2015:   50 Lamictal      0.875 Celexa    0.11 Xanax      1.5 Valium

Feb 15 2016:   47.5 Lamictal   0.75 Celexa      0.0875 Xanax    1.42 Valium    

2/12/20             12                       0.045               0.007                   1 

 

I'm not a doctor. Any advice I give is just my civilian opinion.

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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


06/13 - Celexa 30mg Klonopin 2 mg 

 

02/14 Celexa 30mg (Successfully completed 32 week Klonopin taper dropped 1/8 every two weeks)

Celexa Taper: 06/14 25mg 07/14 20mg 09/14 15mg 10/14 17.5mg 11/14 15mg 12/14 12.5mg 01/15 20mg (updose after going too fast bad w/d for 3-4 weeks after) 05/15 17.5mg 06/15 15mg 07/15 13.5mg 08/15 11.75mg 09/15 10mg 10/15 7.5mg 11/15 5mg 12/15 3.33mg 01/16 2.5mg 2/16 0mg (CT from 2.5mg) 3/16 (3-4 weeks after CT bad W/D symptoms, updose) 1.67mg

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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.


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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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.


2001–2002 paroxetine

2003  citalopram

2004-2008  paroxetine (various failed tapers) 
2008  paroxetine slow taper down to

2016  Aug off paroxetine
2016  citalopram May 20mg  Oct 15mg … slow taper down
2018  citalopram 13 Feb 4.6mg 15 Mar 4.4mg 29 Apr 4.2mg 6 Jul 4.1mg 17 Aug 4.0mg  18 Nov 3.8mg
2019  15 Mar 3.6mg  21 May 3.4mg  26 Dec 3.2mg 

2020  19 Feb 3.0mg 19 July 2.9mg

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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.  :)


Put on Prothiaden for severe depression in 1989.  Recovered.   Prescribed Paxil for another bout of depression around 2000.   Have been trying to taper ever since but always crash about 2 months after getting to zero.   Because of the crashes, for years I thought that there was something wrong with me.   Then found that the crashes were simply withdrawal.   Now following a maximum of a 10% reduction every month or so and ready to slow down any time I feel any symptoms whatsoever.  Feeling good:).

7th Jan 15 - 3.6mg

28th Jan 15 - 3.2mg

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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.


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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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?


<p>Lexapro taper from 7.5mg to 5mg for one week to 2.5mg for one to 2.5mg every other day for one week. Original dose of Lexapro was 10mg. On that for a few years,then cut back to 7.5 with no effects. In total, on Lexapro for about 7 years. Never did much to help with my panic disorder. Cross-tapered with Zoloft 12.5mg for one week, 25mg for one week. Stopped after ten days due to sexual side effects. Off Lexapro completely since end of July 2014.

Update: Aug. 20, 2014 - restarted Lexapro at 3.75mg due to intolerable withdrawal symptoms.

Update: Sept. 16, 2014 - increased Lexapro to 5mg on advice of GP.

Update: Jan. 13, 2015 - requesting Rx for Liquid Lexapro from pdoc on Friday to start taper. Horrible side effects from Lexapro since going back on. Haven't resolved so need to come off.

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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.)


Started on Prozac and Xanax in 1992 for PTSD after an assault. One drug led to more, the usual story. Got sicker and sicker, but believed I needed the drugs for my "underlying disease". Long story...lost everything. Life savings, home, physical and mental health, relationships, friendships, ability to work, everything. Amitryptiline, Prozac, bupropion, buspirone, flurazepam, diazepam, alprazolam, Paxil, citalopram, lamotrigine, gabapentin...probably more I've forgotten. 

Started multidrug taper in Feb 2010.  Doing a very slow microtaper, down to low doses now and feeling SO much better, getting my old personality and my brain back! Able to work full time, have a full social life, and cope with stress better than ever. Not perfect, but much better. After 23 lost years. Big Pharma has a lot to answer for. And "medicine for profit" is just not a great idea.

 

Feb 15 2010:  300 mg Neurontin  200 Lamictal   10 Celexa      0.65 Xanax   and 5 mg Ambien 

Feb 10 2014:   62 Lamictal    1.1 Celexa         0.135 Xanax    1.8 Valium

Feb 10 2015:   50 Lamictal      0.875 Celexa    0.11 Xanax      1.5 Valium

Feb 15 2016:   47.5 Lamictal   0.75 Celexa      0.0875 Xanax    1.42 Valium    

2/12/20             12                       0.045               0.007                   1 

 

I'm not a doctor. Any advice I give is just my civilian opinion.

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DLB

Paxil start September 2003 due to Fluoroquinolone adverse reaction that I wish doc. knew what it was. 10mg. most of the time with a few short runs of 20mg. FAST tapered 3 times and finally hit poop out or a reaction to nsaid's in Nov.2013. Started a 10% taper Jan. 2014 and have been ok until Sept 14 and went through a short hell. Now plodding through and looking for the light with unrelenting insomnia and pain, fog, loss of interests....<p>12/20/14 - .8mg.

1/01/15 - .75 mg.

1/15/15 - .42 mg. better sleep now, hope it continues...

2/11-15 - .25 mg. doing really good!! 2 weeks feel 85% of old me!

3/17/15 .14 mg. Knee pain bad!

4/07/15 .05 mg. this is so small now that I am estimating and just licking it off palm small as a "." 

4/13/15 NOTHING !!!! Took my last little micro dose on 4/12/15. ????????????????

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felin

The pdf on first post in this thread didn't work for me so I looked for article via Google. Is this the same/correct one? Don't want to post something that does not apply.

 

Serotonin Transporter Occupancy of Five Selective Serotonin Reuptake Inhibitors at Different Doses: An [11C]DASB Positron Emission Tomography Study


All that I can give you at this point is what I can remember. Will add more after I've called the zillions of doctors that I've had over the past 30 years. I have spent all day calling old insurance co's, etc to get the long list of doctors names that I once had, so will update this someday. Unfortunately, most records are no longer available. :(

 

Haven't started tapering yet. Will.

 

Currently am on:

  • Cymbalta 60 mg/ daily - actually taking the generic for it. It is called Duloxetine
  • Wellbutrin XL 150 mg/ daily - taking the generic for this. It is called Bupropion XL
  • Naturethroid 3/4 grain/ daily - this is a natural dessicated thyroid med for my Hypothyroidism
  • Relpax only take as needed - for migraines

FINALLY started tapering Cymbalta by 5% reduction May 5, 2016

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Sarabera

These graphs are just a brilliant thing for us in withdrawal. I was delighted to see my old buddy amitryptiline analyzed in the one study ("Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites"). I'm going to chew through that study when I have time. But as pointed out--the curves are all almost identical! Has anyone used this information to create a schedule for withdrawal that will provide even plasma level drops (or % 0f 5HTT binding)--say a 5% plasma level drop with each dosage drop? I'm going to graph that out and see what that would look like.

 

This explains a lot about the difficulties I have had with withdrawal, even though my dosages have been fairly low. I had very little issue with bouncing around between 12.5-25mg, or even 36mg at times. But trying to CT from even a low dose of 6mg. has been impossible for me. I went from 12.5 to 6mg this summer, and never apparently got stabilized--lots of issues with insomnia, stomach issues, etc...Looking at these graphs, I can clearly see why that has been so difficult!


1975--first signs of depression

1981--started on imipramine (Tofranil) for IBS and depression

1983-1986--severe depression, rotated through several drugs, on MAOI for one year, eventually back to tricyclics

1986-1994--chronic low grade depression, on tricyclics

1994-96--severe depression, rotated through several drugs inc. Prozax, Effexor, etc..

1996-2013--chronic low grade depression, SAD, on amitryptiline usual dose 12.5-25mg

     flurazepam (Dalmane) as needed for insomnia

2013--developed temazepam (Restoril) dependance for 2 months, tapered off over 1 month

   started bio-identical progesterone 5 mg., depression has lifted completely to this day

March 2016--forced to c/t both amitryptiline and flurazepam, zolpidem not helpful

reinstated small dose (.5 mg) amitryptiline due to stomach issues and tapering w/titration

June 19th--jumped from amitryptiline--drug free!

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Altostrata

Other antidepressants have been similarly analyzed in other papers. The curves are all similar.


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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SkyBlue

This is absolutely fascinating. 

 

I just joined Surviving ADs and someone showed me the link to this page.  
 
I was wondering if you could help me understand the SERT occupancy concept -- or more specifically, the idea that 
I think that is exactly what is going on with me, and I would love to understand it.
 
The study talks about "minimum therapeutic doses," but I am on only 1.2 mg (!!!) of Paxil and still having extreme difficulty with each tiny dose decrease. I hardly think that 1.2 mg can be considered a therapeutic dose. 
 
So  Altostrata, from your clear explanation, I think what was true for me is that at 60 mg Paxil, 50 mg., 40 mg., 30 mg, no problems with tapering: this was past the saturation point for my receptors, and I wasn't yet hitting my uh-oh point. For me "uh-oh" started at 20, and has been difficult since. 
 
"-at minimum therapeutic doses in every case, there was about 80% SERT occupancy. Even the minimum doses are locking down 80% of your brains reuptake ‘capacity’."
Point here though is that there’s a long way between 0% at no drug and 80% at the minimum dose."
 
Looking at the chart for Paxil/paroxetine, where I am (1.2 mg) there is still 40% SERT occupancy. Well, hello!!!! No *wonder* this has been so difficult. And I can't believe my doctor told me I could "probably just stop" Paxil when I got to 5 mg. !!!!!!
 
What does 40% SERT capacity mean, exactly? That 40% of my neurons are still having serotonin reuptake inhibited by Paxil? 
 
Thanks!!

Current: 2019: 0.04 mg Paxil!! This is real. Soon, after taking Paxil my entire adult life, I will be free.

Long story short: After 18 years on Paxil, "tapered" almost completely off over a month, at doctor's advice in July 2015.

Self-care includes magnesium, reasonable exercise, mindfulness, this forum and nutrition/eating enough food.

Also on 100 mg Zoloft unfortunately!! (which I now will have the knowledge to taper properly)

-------------------------------------------------------------------------------------------

Longer version: On Paxil since 1996--anxiety & depression caused by (undiagnosed) under-eating / eating disorder.

Doctor kept increasing dose, up to 60 mg; it never really helped but said it really was the best "med" for me.

Rapid doctor-led "taper" July 2015, down to 5 mg, with Zoloft as a "cross-taper" = Essentially a cold turkey. 

Severe withdrawal but didn't know it; believed it was my "underlying condition," and kept tapering, 5mg to 4 to 3  to 2 to 1.  

Feb 2016: Found SA! As of June 2016, tapering from 1mg at rate of 5-10% per month, Brassmonkey Slide! 

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Altostrata

"Therapeutic doses" means the dosages found in clinical studies to reduce symptoms of "depression." These tend to be the tablet dosages available, e.g. 10mg, 20mg, 30mg Paxil.
 
(Whether the dosages actually do reduce symptoms of "depression" has produced a huge volume of literature critical of psychiatric drug development.)
 
Although you'll see many references to "therapeutic doses" in journal articles, they are a hypothetical construct, the drug companies' best guesses at what will "work" for the largest number of people. In fact, these are very strong drugs and probably commonly dosed too high, resulting in excess SERT occupancy.
 
These drugs are psychoactives. Some people feel an effect at very low dosages. SERT occupancy is only one factor in causing the neurological changes leading to these effects.
 
If you have been on a drug such as Paxil for a long time, it has caused changes in your nervous system far beyond SERT occupancy. It has changed the inter-relationship of all your hormonal systems, the functioning of your digestive system, your sleep pattern, etc. When you get down to a low dose, which may mean partial SERT occupancy, the rest of your body has to adjust. It is this adjustment that causes withdrawal symptoms.
 
In addition, paroxetine in particular is a very difficult drug to quit, perhaps the worst of all the antidepressants. This is probably because of its effects beyond SERT. For example, it is the SSRI that is the most anti-cholinergic, directly affecting an entire autonomic system.

 

See “It’s Anticholinergic” – What Does That Mean? http://pro.psychcentral.com/its-anticholinergic-what-does-that-mean/002836.html#

 

In medical school pharmacology courses, many of us were taught about cholinergic effects with the mnemonic “SLUD”: Salivation, Lacrimation, Urination, Defecation. I suggest augmenting this with a “C” standing for “Cognition.” If ACh facilitates SLUDC, drugs that are anticholinergic – for example, the tricyclics, Paxil (paroxetine), Cogentin (benztropine), Artane (trihexyphenydil), and Benadryl (diphenhydramine) – are “Anti-SLUD-C.” This means that they cause dry mouth, dry eyes (and blurry vision), urinary retention, constipation, and confusion.

 


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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grandmaD

.. As levels get lower, there is a much greater decrease in % of transporters affected for each little amount of drug taken away.

What exactly does this mean please?  What are "transporters" in simple language?


1995-2007      20mg Aropax/Paxil for pain.  Years of up and down doses

2008                Endep, Lexapro and then Esipram (hell!) CT (oh dear!)

2009                20mg Aropax.  Tried skipping doses for a year (more hell!)

                        2010                10mg.  10% taper.  Lasted 4 months. Crashed again

2011                5% taper. 9mg-7mg (hell got even worse!)

2012                2.5% taper.  6.6mg – 5.6mg (worser still & unbearable)

2013                5% taper.  Big mistake.  5.5mg – 4.6mg  (even worserer)

2014                2.5% taper.  4.9mg – 4.5mg;    2015 2.5% taper 4.4 - 4.0mg

2016                2.5% taper.  3.9mg  Feb 3.8   Mar 3.7  May 3.6   Jul 3.5

2017                2.5% taper.  Jan 3.4;   Mar 3.35;  Apr 3.3; Oct 3; Dec 2.9;

2018                2.5% taper. Jan 2.8; Mar 2.7; Mar: 2.75; Jun 2.7; Aug 2.6; Oct 2.5; Nov 2.4; Dec 2.3

2019                Jan 2.2; Feb 2.1;

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Meimeiquest

Well, this is how I understand it: there are little transporters that carry serotonin back to their starting place after they carry a message across the space between neurons. Basically they are sent off and bind to the neuroreceptor, stimulating it. Then they are carried back by binding to the transporter (called SERT...serotonin reuptake transporter, I can't remember what E is) and riding back.

 

Selective Serotonin Reuptake Inhibitors (SSRI's) are the class of antidepressants that bind to those transporters so they can't carry serotonin and more serotonin therefore stays in the space between neurons. I think...it's late at night :). The lower the dose, the greater percent of transporters are blocked with each bit of medicine. As they get unblocked, there is less serotonin in the space and it is harder for those serotonin messages to get through to the receptors which have become less sensitive because they have been so flooded with serotonin when more transporters are blocked. This probably is a very inadequate and possibly inaccurate explanation...what questions do you have now? The bottom line is it is completely normal for tapering to get harder at the end.


1st round Prozac 1989/90, clear depression symptoms. 2nd round Prozac started 1999 when admitted to dr. I was tired. Prozac pooped out, switch to Cymbalta 3/2006. Diagnosed with bipolar disorder due to mania 6/2006--then I was taken abruptly off Cymbalta and didn't know I had SSRI withdrawal. Lots of meds for my intractable "bipolar" symptoms.

Zyprexa started about 9/06, mostly 5mg. Tapered 4/12 through12/29/12

Wellbutrin. XL 300 mg started 1/07, tapered 1/18/13 through 7/8/13

Oxazepam mostly continuously since 6/06, 30mg since 12/12, tapered 1.17.14 through 8.26.15

11/06 Lithium 600mg twice daily, 2.2.14 400mg TID DIY liquid, 2.12.14 1150mg, 3.2.14 1100mg, 3.18.14 1075mg, 4/14 updose to 1100mg, 6.1.14 900 mg capsules 7.8.14 810mg, 8.17.14 725mg, 8.24.24 700mg...10.22.14 487.5mg, 3.9.15 475mg, 4.1.15 462.5mg 4.21.15 450mg 8.11.15 375mg, 11.28.15 362.5mg, back to 375mg four days later, 3.4.16 updose to 475 (too much going on to risk trouble)

9/4/13 Toprol-XL 25mg daily for sudden hypertension, tapered 11.12.13 through 5.3.14, last 10 days or so switched to atenolol

7.4.14 Started Walsh Protocol

56 years old

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grandmaD

Thanks for your description, however  am still confused!  Transporters sound like buses going to and fro taking serotonin but get hijacked or something...

 

Not to worry, I perfectly understand your last sentence that the lower we go the harder it is and I constantly need to to remember that!  It is still very interesting how all these things work - and don't work when they aren't in their "right order" and just shows we shouldn't play around with our brain with drugs.


1995-2007      20mg Aropax/Paxil for pain.  Years of up and down doses

2008                Endep, Lexapro and then Esipram (hell!) CT (oh dear!)

2009                20mg Aropax.  Tried skipping doses for a year (more hell!)

                        2010                10mg.  10% taper.  Lasted 4 months. Crashed again

2011                5% taper. 9mg-7mg (hell got even worse!)

2012                2.5% taper.  6.6mg – 5.6mg (worser still & unbearable)

2013                5% taper.  Big mistake.  5.5mg – 4.6mg  (even worserer)

2014                2.5% taper.  4.9mg – 4.5mg;    2015 2.5% taper 4.4 - 4.0mg

2016                2.5% taper.  3.9mg  Feb 3.8   Mar 3.7  May 3.6   Jul 3.5

2017                2.5% taper.  Jan 3.4;   Mar 3.35;  Apr 3.3; Oct 3; Dec 2.9;

2018                2.5% taper. Jan 2.8; Mar 2.7; Mar: 2.75; Jun 2.7; Aug 2.6; Oct 2.5; Nov 2.4; Dec 2.3

2019                Jan 2.2; Feb 2.1;

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grandmaD

If you have been on a drug such as Paxil for a long time, it has caused changes in your nervous system far beyond SERT occupancy. It has changed the inter-relationship of all your hormonal systems, the functioning of your digestive system, your sleep pattern, etc. When you get down to a low dose, which may mean partial SERT occupancy, the rest of your body has to adjust. It is this adjustment that causes withdrawal symptoms.

 

In addition, paroxetine in particular is a very difficult drug to quit, perhaps the worst of all the antidepressants. This is probably because of its effects beyond SERT. For example, it is the SSRI that is the most anti-cholinergic, directly affecting an entire autonomic system.

 

See “It’s Anticholinergic” – What Does That Mean? http://pro.psychcent...an/002836.html#

 

 

 

What Alto posted here is good and helps with understanding, thanks

Edited by JanCarol
fixed quotes

1995-2007      20mg Aropax/Paxil for pain.  Years of up and down doses

2008                Endep, Lexapro and then Esipram (hell!) CT (oh dear!)

2009                20mg Aropax.  Tried skipping doses for a year (more hell!)

                        2010                10mg.  10% taper.  Lasted 4 months. Crashed again

2011                5% taper. 9mg-7mg (hell got even worse!)

2012                2.5% taper.  6.6mg – 5.6mg (worser still & unbearable)

2013                5% taper.  Big mistake.  5.5mg – 4.6mg  (even worserer)

2014                2.5% taper.  4.9mg – 4.5mg;    2015 2.5% taper 4.4 - 4.0mg

2016                2.5% taper.  3.9mg  Feb 3.8   Mar 3.7  May 3.6   Jul 3.5

2017                2.5% taper.  Jan 3.4;   Mar 3.35;  Apr 3.3; Oct 3; Dec 2.9;

2018                2.5% taper. Jan 2.8; Mar 2.7; Mar: 2.75; Jun 2.7; Aug 2.6; Oct 2.5; Nov 2.4; Dec 2.3

2019                Jan 2.2; Feb 2.1;

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ChessieCat

I've just found a post in someone's topic by Brassmonkey which contained this explanation:

 

"These drugs work by making physical changes to the nerve endings referred to as "down regulating".  In general the first 5mg affect about 60% of a persons nerve ending while 10mgs affect about 80% .  Increase the dose to 20mg and only 85% are affected. So a lot of changes happen with the first 5mgs."

 

I hope that helps to explain it.


Being very patient.  I'll get there - slowly.  ETA mid 2021

ADs:  25 years - 1 unknown, Prozac (caused muscle weakness), Zoloft/sertraline; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after)

Pristiq:  50mg 2012, 100mg beg 2013 (mild Serotonin Toxicity)

Began tapering Oct 2015  Current from 17 Oct 2020:  Pristiq 0.56 mg (compounded + liquid)

My tapering program

My Intro (goes to my tapering graph)

My website - includes my brief history + links to videos & information on the web

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

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grandmaD

The fact that it affects the nerve endings helps explain a lot of things.  What I have had in the past and am experiencing worse now, is an itchy, prickling sensation which drives me crazy.  It is like someone touching me with stinging nettles in one place, then  in another place, and so on and I figured this had to be nerve ending sensations.


1995-2007      20mg Aropax/Paxil for pain.  Years of up and down doses

2008                Endep, Lexapro and then Esipram (hell!) CT (oh dear!)

2009                20mg Aropax.  Tried skipping doses for a year (more hell!)

                        2010                10mg.  10% taper.  Lasted 4 months. Crashed again

2011                5% taper. 9mg-7mg (hell got even worse!)

2012                2.5% taper.  6.6mg – 5.6mg (worser still & unbearable)

2013                5% taper.  Big mistake.  5.5mg – 4.6mg  (even worserer)

2014                2.5% taper.  4.9mg – 4.5mg;    2015 2.5% taper 4.4 - 4.0mg

2016                2.5% taper.  3.9mg  Feb 3.8   Mar 3.7  May 3.6   Jul 3.5

2017                2.5% taper.  Jan 3.4;   Mar 3.35;  Apr 3.3; Oct 3; Dec 2.9;

2018                2.5% taper. Jan 2.8; Mar 2.7; Mar: 2.75; Jun 2.7; Aug 2.6; Oct 2.5; Nov 2.4; Dec 2.3

2019                Jan 2.2; Feb 2.1;

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bubbles

I tabulated some of the data from one of the graphs. I took the first sertraline graph and came up with this. It's incomplete - I didn't plot it all. :) This is VERY rough - I enlarged the graph on my screen and held up envelopes to the screen to try to work it out. To do that I'd print it out large and do some careful measuring. I started at 75mg because I was on that dose for the longest time. :) The next point is 50mg, just because. :)

 

75mg     85%

50mg     82%

45mg     80%

40mg     78%

35mg     77%

30mg     75%

25mg     70%

20mg     67%

15mg     60%

10mg     54%

5mg       36%

0mg       0%

 

Specifically - look at what happens at about the 12.5mg mark, which is half of a 25mg tablet (being the lowest dose available in the US, I think?) - it's going to be a bit under 60% - let's call it 57%.

 

I'd think that there wouldn't be many people on less than, say, 25mg or 12.5mg (being half a 25mg tablet) so I imagine that would be the smallest dose for which they'd really have data. So the curve must be extrapolated and calculated? I wonder what is really happening down at the small end of things.

 

Anyway, just musing. It certainly does suggest that the drop from 5mg to 0mg might be more problematic than the drop from 75mg to 50mg. 


My thread here at SA: https://www.survivingantidepressants.org/topic/1775-bubbles/page/14/

2005 St John's Wort / 2006-2012 Lexapro 20mg, 2 failed attempts to stop, tapered over 4.5 months in early 2012

January 2013 started Sertraline, over time worked up to 100mg / July 2014 dropped from 100mg to 75mg, held for six months

2015 tapered to 50mg over several months, held for several months, some more drops

2016 Feb 35mg, 6 Mar 33mg, more drops (note big drop (calc error) & up to 25mg), more drops (about 2mg at a time)

2017 - more small drops, more long holds

2018 March at 11mg;  April 20 9mg; June 11 8.1mg; (July 10 7.7mg / July 18 7.3mg); ( Sept 2 7.2mg, Sept 5 7.1mg, Sept 9 7mg); 30 Sept 6.5mg, ? 6mg, 23 Nov 5.5mg) 19 Dec 5mg

2019 (micro drops over two weeks 24 Mar 4.9mg, 28 Mar 4.8mg, 31 Mar 4.7mg, 4 Apr 4.6mg, 7 Apr 4.5mg / 22 April 4.4mg, 26 April 4.3mg, 2 May 4.2mg, 5 May 4.1mg, 9 May 4mg), 3 Oct 3.9mg, (20 Oct 3.8mg, 27 Oct 3.7mg, 3 Nov 3.6mg), 24 Nov 3.5mg, 8 Dec 3.4mg, 15 Dec 3.3mg, 22 Dec 3.2mg

2020 19 Jan 3.1mg, 26 Jan 3.0mg; 1 Mar 2.9, 7 Mar 2.8, May (some drops here) 24 May 2.5, May 29 2.4, June 21 2.3, June 28 2.2mg,  July 4 2.1mg, July 24 (or maybe a bit before) 2mg

Current Sertraline: July 24: 2 mg / Armour Thyroid / endless allergy meds, erg

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woof

I beleive this article and the the incredible graphs within it, explecitly depict what ADs do at various doses. IMO reading this article should become the standard of care and a mandatory part of informed consent for health care providers and their patients when taking, tapering or considering taking ADs. 

 

Prior to reading this article I was totally unaware of the the exponential fashion in which these drugs work at doses which are much, much lower than those which are typically prescribed.

 

Please do not do this, but this is in fact what happened to me. I was taking 40mg Cymbalta/day for four years.  One day I decided to cut my dose in half and take only 20mg Cymbalta/day; this was without any taper whatsoever.  I never experienced any wd symptoms at all. 

 

Six years later, I thought that could simply do this again (same dosage right :blink: ) so I "cold turkey" stopped the 20mg Cymbalta/day, just as I had done in the past, but this time I crashed and burned BAD! :o : 10/10 severe: insomnia, anxiety, restlessness/akathesia, Tinnitus.    

 

So, slow and low is good.


If on a Benzo for a relatively short period of time, such as less than 6-12 months, one may want to consider tapering off their Benzo first (please see Will Hall's book on Harm Reduction)

 

Prior to commencing with an AD taper please consider what problems the AD is causing, as tapering is an extremely serious endeavor.   

If one has been on an AD for more than 10 yrs. please consider the potential long term negative consequences of AD withdrawal prior to tapering. (please see Drs. Healy, Glenmullen and Shipko) 

Prior to re-starting an AD taper, please do not resume tapering until all w/d sx's from any prior taper, especially CT, have resolved. 

 

2004 - Dec. 2015,  Cymbalta 20mg/d  for neck pain - Never had problems with Cymbalta.   Dec 2015, CT 20mg/d Cymbalta.  5 weeks later reinstated 20mg/d Cymbalta - without increase in CT sx's.   

Feb 2016 STARTED VALIUM 25mg/d for CT Cymbalta wd sxs.    Jan-April 2016 Held Cymbalta 20mg/d - doing pretty well (AM 3/10 anxiety and 3/10 tinnitus)

April 2016, CT Cymbalta sx's had not yet resolved and I prematurely tapered 10% q 4 wks x 3 mos.  After 3rd cut developed 10/10 wd sx's of Anxiety, Anhedonia, Anorexia, Panic attacks, dark, incresaed Valium to 28mg/d. 

November 2016, after 3 cuts, UP-DOSED all (41 beads) back up to 20mg (193 beads total) Cymbalta - from , dark to light.

VALIUM TAPER: Jan 2017 28mg to March 2019 Zero   Cymbalta has partially stabilized and helped with the Valium taper.  The only sx I have now is 3/10 Tinnitus, which I only notice when it is quiet.

http://survivingantidepressants.org/index.php?/topic/11900-woof-cymbalta-re-stabilization-after-cold-turkey-withdrawal/  Benzo Posts http://survivingantidepressants.org/index.php?/topic/11951-woof-valium-scheduling-and-dosage-with-cymbalta-wd-symptoms/

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Altostrata

Our esteemed scallywag has made a chart showing what skipping doses does to your blood level of Cymbalta, for example:
 

I'm seeing a fair amount of discussion with newcomers about skipping doses.  I've created a spreadsheet that shows the % concentration decay, comparing daily dose, alternate day dosing and skipping 2 days. This chart is for Cymbalta (duloxetine) or a drug that has a 12-hour half-life.
 
The chart is in a spreadsheet (.xlsx).  I'm going to refine it, maybe showing every 12 hours instead of every 24 and setting it up so that any half-life can be "inputted." Then I'll attach it to another post.
 
The blue line is taking daily doses; green is every other day dosing; red is every 2 days.

 

scallywag_skipping_doses.jpg
 
http://www.mediafire.com/view/ni0hmq4si6qatlq/scallywag_skipping_doses.jpg

Edited by Altostrata
updated link

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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scallywag

For some reason, Alto's link isn't showing.  It's in my attachments:  Click for chart

 


This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.
1997-1999 Effexor; 2002-2005 Effexor XR 37.5 mg linear taper, dropping same #beads/week with bad results

Cymbalta 60 mg 2012 - 2015; 2016: 20 mg to 7 mg exact doses and dates in this post; 2017: 6.3 mg to  0.0 mg  Aug. 12; details here


scallywag's Introduction
Online spreadsheet for dose taper calculations and nz11's THE WORKS spreadsheet

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ChessieCat

I found this explanation by NZ in a post to Otter:  Regarding the SERT diagram

 

 

 


....
 
Regarding the SERT diagram.
Here's my take on it.
The SERT study (and its diagrams) is not about tapering per se. However it does provide a validation for the tapering regimen that is recommended on this site. And what people have found to provide the best chance of getting of these drugs and staying off.
10% of the previous dose per month tracks according to a decreasing geometric progression and provides a very close approximation to the SERT graphs. (a kind of  logrithmic curve only we are travelling in reverse direction) Which is what the mid section of these graphs follow.
Recall: Abrupt changes in serotonin levels is what can trigger suicidal and homicidal ideations.
So we do not want to taper in a manner that triggers abrupt changes in serotonin levels.
 
Note: The graph does not follow an arithmetic progression ie a straight line trajectory.
Hence inferring the safest way to taper and the way to follow the graphs is to make each drop smaller than the previous drop. (Done by making each successive dose a % of the previous dose, each successive drop will be smaller)
This has proven the best way to get off the drugs. It allows the brain time to adjust to a smaller dose and remain stable.
 
Note also how critical it is at lower doses ...the serotonin occupancy is very dose sensitive at lower levels ie at lower dose levels small changes have big effects unlike at large doses there is not so much of a change. Perhaps because there is an over-saturation of the drug.
This is why many people can get from 60 to 20 say without too much trouble but struggle to go lower after that.
 
Similarly you appear to have gotten from 200 to 100 okay (emphasis on 'appear to' as wdl symptoms can be delayed and we dont know what may be currently in the pipeline) but sooner or later if you don't slow down you will crash heavily.
In other words the lower you go the slower you must go. Following a straight line trajectory may eventually cause you to fall off a cliff.
 
Online support groups such as this have found that 10% of previous dose (not the original dose)  is the best way to taper and minimize withdrawal symptoms. Some may be able to go faster some have to go even slower.
 
My long pontification can be summed up in one sentence:
Alto: We show the receptor occupancy curve in reverse to suggest you have to come off the drugs slowly to match the curve and avoid causing a precipitous slide towards the end.
Edited by Altostrata
added quote

Being very patient.  I'll get there - slowly.  ETA mid 2021

ADs:  25 years - 1 unknown, Prozac (caused muscle weakness), Zoloft/sertraline; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after)

Pristiq:  50mg 2012, 100mg beg 2013 (mild Serotonin Toxicity)

Began tapering Oct 2015  Current from 17 Oct 2020:  Pristiq 0.56 mg (compounded + liquid)

My tapering program

My Intro (goes to my tapering graph)

My website - includes my brief history + links to videos & information on the web

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

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KtKat

Looking at the graphs of receptor occupancy.... I would almost try to plot the receptor occupancy to work out dosage reductions. 

 

For example, looking at the Citalopram graph, if it was decided that a safe drop in receptor occupancy was 5% per dose change  (I'm sorry, I can't stick the picture in because I'm not that techy) then the dosages look as follows

 

80% occupancy      20mg dose         

75%                        12.5mg           37.5% drop in dosage

70%                        9mg               28% drop in dosage

65%                        7mg               22% drop in dosage

60%                        6mg               14 % drop in dosage

55%                       5mg               etc....

50%                       4mg

 

From that point it becomes hard to interpret because of the resolution of the image and the scale of the graph, so I can't really calculate the lower numbers.

 

 

I'm not putting this out there to try and change the recommendations, stick with 10%, slow and steady wins the race. It may however explain why I didn't feel any withdrawals when I dropped my escitalopram from 10mg to 5mg in one go, but lost the plot completely when I stopped taking the medication at 1.25mg (extrapolating from the citalopram graph I estimate the occupancy dropping from 80% to about 70% with the first drop, but from 40% to nothing with the second, my system could handle the 10% drop, but not 40% in one hit - and my extrapolations are based on the escitalopram being twice the strength of citalopram for ease of interpretation, i.e. 10mg Escitalopram +20mg of citalopram).

 

If there were to be some more research into receptor occupancy I think it would be very interesting. 

 

Additional link 

http://link.springer.com/article/10.1007/s00213-006-0666-y?view=classic

looking at this abstract, it seems as though Escitalopram has more than double the binding ability of citalopram - at a 10mg dose, escitalopram had an 81% occupancy, while 20mg of citalopram was only 64%.

Also interesting was that the plasma levels of the s-enantiomer were the same, suggesting that the r-enantiomer (the other half of the chemical which is in citalopram but NOT in escitalopram) has some level of inhibitory effect over the active part of the drug. Very interesting

Edited by KtKat

Started 10mg Escitalopram March 2013
Stopped Escitalopram cold turkey December 2013 (Unsuccessfully)
Restarted 10mg Escitalopram February 2014
Started tapering May 2016 - 5mg
Estimated drops - 4mg, 3mg, 2.5mgOctober 2016 - 1.25mg
Stopped 19 Dec 2016
Withdrawals from 27 December - Anxiety, Insomnia, Nausea, Diarrhea, Headache (1 day), inc heart rate
7 Jan 2017 reinstated 1mg/day escitalopram

4 Feb 2017 - inc to 1.25mg Escitalopram after some feelings of depression returning

Currently experiencing generalised anxiety in waves

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data17

I disagree that the exponential relation between drug dose and receptor occupancy at low drug levels is the real reason for a slow taper, at least not in many long-term users. That is because the number of receptors is not fixed, but changes slowly over time.

 

I am tapering an antipsychotic that blocks dopamine receptors and over time (decades) I have had to gradually increase the dose, reflecting an increase in dopamine receptors, to get the same effect. In other people, the drug may have become less effective at the same dose. Similarly to SERT graphs, the clinically effective doses of antipsychotics blocks 60-80% of receptors, so lies on the plateau part of the dose vs occupancy curve.

 

Suppose I am taking a dose that is just above the exponential part of the occupancy curve. If I then cut the dose, the withdrawal is due to two things - there is reduced receptor occupancy due to going onto the exponential part of the curve, but also I have a supersensitive system due to the extra receptors and this is what creates the long-lasting effects, because receptor numbers change quite slowly.

 

However, if I hold for a few weeks or months, the number of receptors decreases and once again 60-80% are blocked - even though I am now at a lower drug dose - so the reduction in dose has not put me permanently onto the exponential part of the occupancy curve, I have gone back to the plateau part. Next time I cut, the same thing happens - acute withdrawal, receptors decrease, but overall I remain at 60-80% receptor occupancy.

 

I still agree with small cuts, but it is because of the slow rate of change of receptor numbers, not because of exponential changes in receptor occupancy.

 

Eventually the dose will be so low, that I decide to jump. But by that time, the hope is that the receptor numbers will be normal and so I won't be dealing with a supersensitive system.

 

(Of course this isn't the whole story, changes may take place at different rates in different parts of the brain, there are other physical changes, learned changes and collateral life damage from decades on drugs) 

 

 

 


  • 1991-1998 Haldol, olanzapine; 1996-2014 diazepam; 1999-present procyclidine 12.5mg, trifluoperazine (Stelazine/TFP)
  • 2015 - Oct 2017 :taper Trifluoperazine (TFP) 7.7mg to 3.4mg 
  • Nov 2017: TFP suddenly unavailable - CT! 
  • Jan 2018 :TFP back in stock as liquid ~4mg per day 
  • June 2018:~3mg TFP 
  • Oct 2018 :~2mg TFP 
  • Mar 2019: ~1mg TFP
  • Apr 2019: ~0.7mg TFP
  • 21st May: 0.4mg

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Ryder
On 4/27/2014 at 5:47 AM, Rhiannon said:

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 blockers" "oh it's this piece" "oh it's that piece"... saying not "well, maybe, it's a guess, a little bit of it could maybe work this way" but "this. is. how. it. works."

 

NO. We don't know that. We don't understand it well enough yet to say things like that with any authority. Our knowledge is teeeeeeny. It's not that simple, we aren't there yet, we don't have good models, we don't have any models, these are all speculative hypotheses which will undoubtedly inevitably be proven incorrect or drastically and tragically incomplete eventually. (That much we do know from experience.)

 

This stuff is not only not proven, we don't even know enough to make good guesses, and we need to keep that in mind while we play with it and learn more. And NOT play with human lives and minds based on our extremely imperfect knowledge and our definitely-incomplete ideas.

 

That is the same kind of hubris that has gotten our planet into the shape it's in today.  The same hubris that has gotten most of us who are here on this forum where we are today.

 

We humans are not as smart as we think we are. Not even close. 

Could not have put the words better myself. On top of this, people are using Dr Google to self-diagnose and this makes things worse. The general consensus of this whole forum, whether you on the worst drug to the best drug is to take it easy. Who knows, maybe 10% is too much for different people. The core feeling for most people here is to go gradually.  

 

 

 

 


 Cymbalta, Zyprexa, Seroquil, Rispiridone, Valium, Zoloft, Clonazepam,. + 1 other Benzo. Total 11 yrs.

·           April 9th 2018 Hospital. 50mg Zoloft > 0 discontinued. 6mg Clonazepam > 2.5mg over 8 weeks stay.

           October 25th 2019: Hospital: Stopped Clonazepam 1mg > Bridged to 20mg Diazepam.

           

           Anafranil: 1st May 18': 150mg, 1st June: 150mg. 23rd June: 125mg. 6th July: 100mg. 12th July: 75mg 22 July: 62.5mg. 5th August 18: 50mg. 10th November 2018: 45mg. 25th August 2019: 40mg.  Sep '15: 37.5mg.              1st November 2019: 100mg (Re-instated during hospital). 25 morning / 75 night. 22/01/20: 95mg. 03/02: 90mg

                          

        Clonazepam: (k) 1st May 18: 2.5mg. 6th July 2018. 1.5mg K. 03 August 2018: 1.25mg K. 17th August > 10 November 2018: 1mg K. Jan - August 2019: (Dosing between 1mg and 0.87mg)  September 10 2019: 0.9mg. Discontinued 25th October 2019.

 

        Diazepam (V): 25th October 2019, 20mg. 22/12 19mg. 4/04/20: 18mg

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ChessieCat

This is a graph representing a "perfect" 10% taper of the previous dose with 4 week holds.

 

776391214_PerfectTaper.png.f16551da35c66ed2616e7cdd534b7505.png

Edited by ChessieCat
reattached graph

Being very patient.  I'll get there - slowly.  ETA mid 2021

ADs:  25 years - 1 unknown, Prozac (caused muscle weakness), Zoloft/sertraline; citalopram (pooped out) CTed (very sick for 2.5 wks a few months after)

Pristiq:  50mg 2012, 100mg beg 2013 (mild Serotonin Toxicity)

Began tapering Oct 2015  Current from 17 Oct 2020:  Pristiq 0.56 mg (compounded + liquid)

My tapering program

My Intro (goes to my tapering graph)

My website - includes my brief history + links to videos & information on the web

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

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RachelSusan

Thank you ChessieCat for the graph.

RS
 


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 19, 2017 reduced to 12.0 mg (4%).   Feb 9 2017 reduced to 11.0 mg (8%). March 1 2017 to 10.0 mg (9 %).  March 21 2017  to 9.5 mg (5%). April 1 2017  to 9.0 mg (5.3%). April 10 2017 to 8.5 mg (5.6%). April 22 2017  8.25 mg (2.9%). April 29 2017  8.0 (3.0%). May 6 2017  7.75 mg (3.1%).  May 14 2017  7.5 mg (3.2%). May 20 2017 to 7.25 mg (3.3%). May 27 2017 reduced to 7.0 mg (3.4%). June 10 2017  to 6.75 mg (3.6%). June 17 2017 to 6.5 mg (3.7%). June 24 2017 6.25 mg (3.8%). July 1 2017 reduced to 6.0 mg. July 8 2017 5.75 mg. July 15 2017 5.5 mg. July 22 2017 5.25 mg.  Aug 5 2017  5.0 mg.  Dec. 9, 2017  4.75 mg (5%).  Feb. 10, 2018 4.50 mg.   March 15, 2018 4.375 mg (2.8% decrease). April 3, 2018 4.25 mg (2.9%). May 14, 2018 4.125% (2.9%). June 16, 2018 4.0 mg (3.0%).  July 21, 2018 3.875mg. August 11, 2018 3.75mg (3.2%). Sept. 12, 2018 3.62mg (3.3%).  Oct. 13, 2018 3.5mg (3.4% decrease). Nov. 29, 2018 3.375mg (3.6% decrease). Jan. 20, 2019 3.25 mgFeb 16, 2019 3.125mg (3.8%). April 7, 2019 3.0mg (4.0%).  May 18, 2019 2.875mg (4.2%). June 22, 2019 2.75mg (4.3%)July 27, 2019 2.62mg (4.5%). August 18, 2019 2.5mg (4.8%). Sept. 14, 2019 2.375mg (5.0%) Oct.19, 2019 2.25mg.  Nov. 16, 2019 2.12mgDec. 7, 2019 2.00mg (5.9%). 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.

OTHER MEDICATIONS: Gabapentin - 900 mg since July 2016, Prednisone  5mg.  QVAR Inhalant,  Supplements: Vitamin D, Probiotic, and Fish Oil.

 

 

 

 

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Frogie
2 hours ago, ChessieCat said:

post-5985-0-07114400-1496291012_thumb.jpg

 

This is a graph representing a "perfect" 10% taper of the previous dose with 4 week holds.

Can I ask a "dumb" question? Has there ever been a perfect 10% taper?


PREVIOUS medications and discontinuations: Have been on medications since 1996. 

 Valium, Gabapentin, Lamictal and Prilosec from 2000 to 2015 with a fast taper by a psychiatrist.

 Liquid Lexapro Nov, 2016 to 31-March, 2019 Lexapro free!!! (total Lexapro taper was 4 years-started with pill form)

---CURRENT MEDICATIONS:Supplements:Milk Thistle, Metamucil, Magnesium Citrate, Vitamin D3

 Xanax 1mg three times a day June, 2000 to 19-September, 2020 Went from .150 grams (average weight of 1 Xanax) three times a day to .003 grams three times a day.

19-September, 2020 Xanax free!!!

 

 

I am not a medical professional. The suggestions I make are based on personal experience.

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