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Why taper? Paper demonstrates importance of gradual change in plasma concentration

tapering

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#73 scallywag

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Posted 12 June 2016 - 07:45 PM

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 (brand name), 60 mg 2012 - 2015; 20 mg to 7 mg in 2016, exact doses and dates in this post;
2017: 6.3 (58 beads) Feb. 1; 5.6 mg (52) Feb. 22; 5.4 mg (50) Mar. 15; 5.1 mg (47) Mar. 25; 4.9 mg (45) Apr. 5;
Current dose: 4.5 mg (42) 2017-Apr-14
+ Supplements: fish oil (1500 mg EPA/500 mg DHA), Vitamins: D3, K2, C; Minerals: Mg, Se, Cr, I, V
scallywag's Introduction
Online spreadsheet for dose taper calculations and nz11's THE WORKS spreadsheet


#74 LexAnger

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Posted 12 June 2016 - 09:07 PM

thanks so very much Scallywag!

This is a great chart!

Due to sudden and severe drug resistance in the middle of my micro taper of Lexopro, I had to spread my daily liquid over 12 hours by taking a drop every 30 minutes, otherwise the after dosing reaction is too strong to bear ( putting me into coma like status )

I have always wondered / worried about the impact of this manner of dosing.

This is an extreme way of splitting daily doses to 2 times like morning and evenin.

Anyone has any thoughts?
<p>2009 Mar.: lexapro 10mg for headache for 2 weeks.2009-2012: on and off 1/4 to 1/3 of 10mg2012 June--2013 Jan,: 1/4-1/3 of 10mg generic, bad jaw pain2013 Jan-Mar: 10 mg generic. severe jaw and head pain; Mar--Aug. started tapering (liquid ever since) from 10 to 5 (one step) then gradually down to 2.25 mg, first ever panic attack, severe head/jaw pain2013 Aug.: back to 2.75 mg; Nov: back to Brand Lex. 2.75mg -- 3mg, slight improvement with pain2014 June: stopped PPI, head pressure/numbness. up-dosed 4.5mg, severe reaction mental symptoms added on2014 Aug--2015 Aug: Micro taper down to 3.2mg, .025mg (<1%) cut holding 2-3 weeks.2015 Aug 15th, Accidental one dose of 4.2mg. worsening brain non-functional, swollen head, body, coma like, DR2016 Feb., started fast taper for the drug toxicity caused by the one dose of 4.2mg, dosing 10am through 11 pm everyday2/13--3.2mg, 3/15-- 2.9mg, 4/19-- 2.6mg, 6/26--2.2mg, 7/22 --1.9mg, 8/16--1.8mg,8/31--1.7m g, 9/13--1.6mg, 9/27--1.5mg, 10/8--1.4mg, 10/14--1.3mg, 11/1--1.2mg, 11/29--1.1mg, 12/12--1mg, 12/22--0.9mg2017: 1/7--0.8mg, 1/15--0.7mg, 1/17--0.6mg, 1/20--0.52, 1/21--0.4mg, 1/22--0.26, 1/23--0.2, sliding Down to 0.13mg by 2/13, then 0.07mg since 2/18, 0.06mg 2/20-3/17, 0.13mg 3/18

#75 Altostrata

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Posted 13 June 2016 - 12:53 PM

Thanks, scallywag. I also updated the link in my post.

 

LexAnger, that split dosing introduces the drug gradually and reduces the initial spike scallywag's chart shows for daily dosing.


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#76 woof

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Posted 08 July 2016 - 02:41 PM

Considering drugs with a short half life such as Cymbalta, with a 12 hour half life, does anyone know of any benefit to taking, the divided daily dose, twice a day? 

 

Might this help to keep the drug availability within an even narrower range, increase stabilization and hopefully further decrease wd sx's?


2004-2015 Cymbalta 20mg/d No problems at all with Cymbalta, I just wanted to get off of all meds.  Nov, 25 2015 CT 20mg/d Cymbalta (194 beads)   

Jan 2016 Reinstated 20mg/d Cymbalta (194 beads) 5 weeks after CT

Jan-April 2016 Held Cymbalta 20mg/d for 4 months. All wd sx's gone, except: 4/10 AM anxiety 9-1:30 only after 7:30 AM Cymbalta, 2/10 tinnitus & 2-4 AM waking then back to sleep. 

April 21 2016 Prematurely CUT -Cymbalta 20-18mg (194-19 = 175 beads) - AM anxiety resolved :)  May 21, 2016 cut to (158 beads) 16mg-stable,

July 04, 2016 cut to (143 beads) 14.5mg and had 10/10 wd sx's  Anxiety, Anhedonia, Anorexia, Fear, dysphoria, could not go back to sleep after 1:30 AM wake-up.

Nov 29th 2016 UPDOSED (41 beads) Cymbalta to 20mg (194 bead) all sxs except tinnitus virtually gone. 

I plan to stay on 20mg/d Cymbalta.  Nothing but improvement since updosing.  Stable with no anxiety and greatly improved sleep as of March 8th 2017

FEB 2016 STARTED Valium 25mg/d for the CT Cymbalta wd sxs.   August 2016 Increased Valium to 28mg/qhs, due wd sx's from July 4, 2016 Cymbalta cut.

Jan 1, 2017  Cut Valium 28mg qhs 28mg-3mg=25mg.    March 11,2017 25mg-2mg=23mg   Plan to decrease Valium 10% per 4 weeks as tolerated.  Fish oil

http://survivinganti...key-withdrawal/  Benzo Posts http://survivinganti...ta-wd-symptoms/

 

 


#77 ChessieCat

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Posted 31 July 2016 - 05:21 PM

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, 02 January 2017 - 01:49 PM.
added quote

Podcasts:    Let's Talk Withdrawal

 

Antidepressants:  25 years - 1 unknown, Prozac (caused muscle weakness), Zoloft; Cipramil CTed (very sick for 2.5 wks soon after)

Pristiq:  50mg mid 2012, 100mg beg 2014 (mild Serotonin Toxicity)     Current:  Pristiq 25mg (from 21 April 2017)

 

Tapering history & graph

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

 

I've still got a way to go ... but I've already come a long way!!!

 

PLEASE NOTE:  I am not a medical professional.


#78 Lawyerliz

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Posted 02 January 2017 - 11:56 AM

The occupancy thing is really facinating, and it mkes intuitive sense.

#79 KtKat

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Posted 08 January 2017 - 03:32 AM

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...-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, 08 January 2017 - 03:41 AM.

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


#80 oskcajga

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Posted 02 February 2017 - 08:41 PM

Very interesting study, this definitely emphasizes the importance of a slow taper, especially at low to moderate doses.  Makes me hate the moronic psychiatrist even more than I already did.  Told me to "bite the bullet" at lower doses of Cymbalta - he clearly had no idea what he was doing.  I wish I could sue him into oblivion, but I'm not a wealthy man, and the statute of limitations is probably long gone - it would be worth it just to see him in court though.


8 Words of Wisdom about Adverse Effects and Psychiatric Drug Withdrawal Syndrome:

 

1.  Please do learn about this condition by thoroughly reading 1) Dr. Healy's website and SurvivingAntidepressants.

2.  Please read books like: 1) Anatomy of An Epidemic and 2) Mad in America.

3.  Success Stories do exist.

4.  Please be extremely cautious about reinstatements, recreational drugs, supplements.  Even low doses can complicate matters.

5.  Transfer all financial assets into your own name (hint: relationships end).  Do not spend money wastefully.  Keep your job as long as possible.

6.  Psychiatric drug "withdrawal" and adverse effects are serious neurological reactions to powerful "drugs" - do not take this condition lightly.

7.  These conditions almost never recognized by any medical doctors - hospitalization/appointments can be futile/potentially injurious.

8.  PSSD, anhedonia (no emotions), memory loss, brain zaps, etc are scary - don't worsen them by taking more drugs, supplements, and medications.

 

Stimulant free since September 20th, 2014; SSRI free since September 1st, 2013






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