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


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ANTI-PSYCHOTIC    OCCUPANCY OF 5-Ht -2A RECEPTORS

A-typical Anti-psychotic RISPERIDONE  RISPERDAL

 

Risperidone proved to be unique in its receptor occupancy profile when compared to haloperidol (9) and clozapine (2) (another atypical antipsychotic). Apart from binding primarily to 5-HT2A receptors (clozapine binds primarily to histamine H1 receptors and haloperidol to D2 receptors), risperidone had a shallow occupancy curve at D2 receptors in the striatum and mesolimbic regions – suggesting a gradual increase in the occupancy of the receptor with increasing doses (Figure 18). 159 Risperidone occupied 50% of 5-HT2A and dopamine D2 receptors at a dose of 0.0075 and 2.5 mg/kg s.c., respectively. At a dose at which 50% of D2 receptors are occupied, there is full occupancy of 5-HT2A sites, which 54 as previously described, can be helpful against negative symptoms.8,160 Also, the gradual occupation of D2 receptors suggests that at a lower dose and with partial occupation, risperidone might be helpful against positive symptoms without inducing EPS

 

I found this at A study of the action of risperidone at 5-HT2A receptors (vcu.edu)  pg 53

A study of the action of risperidone at 5-HT2A receptors

 

Could you guys tell me what this means.  As far as I can tell what it means to me is that 1/  I have to get down ot .0075 mgs  from a normal .5mgs dosage to even begin to feel half the affects of the comming withdrawal.  2/  I have to get down to some rediculous small amount with tweezers to get a greater withdrawal affect.  so something like .00025  How am I supposed to get that low.  I think I am going to have to jump off a cliff at the very end of the withdrawal process.  What do you guys think or know about this.

 

I just wanted to add that I wonder if going on Seroquel at a very low dose is easier to detox from than risperidone.  Does anyone know which anti-psychotic is easiest to withdrawal from?

Edited by MarkDavid
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Lamictal 100mgs X 2 day   April 1999 - Present   Bi-Polar

Gabapentin 800mgs X 2 day April 2008 -2013    Bi-polar

Gabapentin 800mgs X 3 day 2013 - Present

Geodon (Ziprasidone) 40mgs 2020-2021 STOPPED!! November 2021

Alcohol 1998 -September 30th 2021  Alcoholism  2 1/2 year breaks when institutionalized or in a program 2004 - 2008 2 years 8 months 2011 - 2013 Sober

Metoprolol 2016 - 2021   Heart condition

Vistaril (Hydroxyzine) 50mgs at bedtime 2018 -2021 Prescribed with Risp for better sleep

Risperidone (Risperdal) 1mg 2017 -2018   .5mg 2018 -2020

Risperidone .375mgs 11/25/21 - 12/13/21  (18days) Risperdal .333mgs ?  12/14 - 12/16/21  (2 days)  

Risperdal .315mgs        12/17 - 12/26/21  Holding here now for the last 10 days (if I go lower I get insomnia)  Risperdal .25 12/28  12/31 (3days)

I know the lower I go on the Risperdal the slower I will need to cut down and hold for at least a month at a time.  I plan to hold at .25 for 3 months when I get there.  Correction, I am reconsidering trying to tapper again after one months.  So the tapper may begin again on 1/28/22

 

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  • 3 months later...
On 10/28/2017 at 3:13 PM, ZK2015 said:

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

Thank you so much for this formula, ZK2015 - it has helped me immeasurably.  I am kind of an Excel geek, so I used your formula for mirtazapine and modified it as follows:

 

mirtazapine occupancy% = 86*dose*2.66/1.94+dose*2.66. 

 

The 2.66 multiplier is because 7.5 mg of mirtazapine is roughly equivalent to 20 mg of Prozac.  Obviously, the drugs aren't equivalent, because at low doses mirtazapine has much more affinity for H1 and it's not an SSRI (it's a serotonin receptor agonist), but the issue of occupancy is similar.  I could not find occupancy curves for mirtazapine, but did find an article that said it can have up to 95% occupancy at 7.5 mg. This is the dose inflection point for this drug.  From 7.5 mg on down the occupancy is hyperbolic.

 

This showed that my 10% tapers (from 22.5 to 7.5 mg) were more or less linear in terms of occupancy rate: 1% occupancy per 10% taper.  My WD symptoms were manageable.  But when I tapered at 10% (from 7.5 mg to 6.75 mg) my WD symptoms were off the charts.  Along with my usual (intensified agitation, irritability, anxiety), I have shaking, nausea, diarrhea, headache - all starting 21 days in.  Yuck.

 

When I found Zk2015's formula I could see that at 7.5 mg mirtazapine shifts from linear to hyperbolic, so 10% taper resulted in a 2.6% decrease in occupancy.  That is 2.5 x higher than what happened when I came down from the higher doses. No wonder I am having such a hard time! 

 

Armed with with this new information, I have plotted a much safter taper schedule for myself that will have me shedding 1% occupancy with every taper.  

 

Thanks so much for this resource.

Antidepressant (mirtazapine):

2015-2016: 22.5 mg 

2016/17: 10% taper / month to 15 mg

2018: 10% taper / month to 7.5 mg

2018-2022: 7.5 mg 

7.5 mg > 6.75 mg (08.03.22) > 6.55 (19.08.22) > 6.375 (12.09.22) > 6.12 (10.10.22) > 5.83 (04.11.22) > 5.51 (29.11.22) > 5.3 (10.03.23) > 5.2 (07. 04.23) > 5.1 (21.04.23) > 4.91 (15.09.23) > 4.75 (03.09.23) > 4.56 (27.09.23) >  4.35 (27.10.23) > 4.14 (22.11.23) > 3.94 (18.12.23) > 3.75 (17.01.24)

Other meds:

- since 2007: 2.5 mg Zoplicone, pn, for sleep 

- 1994-2022: 12.5 mg trazodone pn for sleep. Developed serotonin toxicity with mirtazapine @ 6.75 mg; CT trazodone Apr. 9, 2022. 

Supplements:

- omega-3 (900 mcg / day); Mg bisglycinate (150 mg 2x day); vitamin D; probiotic (Flora Symmetry), vitamin C (500 mg/day) 

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  • 1 month later...
  • Moderator Emeritus

 

Scrountz gives a fairly simple explanation of SERT occupancy:

  

On 4/29/2022 at 1:41 PM, Scrountz said:

Even low doses of SSRIs can have a pretty potent effect on the nervous system. A lot of doctors don't appreciate that the minimal dose of an antidepressant medication is still really strong. This link here illustrates this. If you don't have a science background it can be a bit hard to understand, but basically even the lowest dose of an antidepressant still fills about 80% of the receptor sites that its supposed to. Increasing the dose of medication does not increase its effectiveness proportionately.

 

.

* NO LONGER ACTIVE on SA *

MISSION ACCOMPLISHED:  (6 year taper)      0mg Pristiq  on 13th November 2021

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 from Oct 2015 - 13 Nov 2021   LAST DOSE 0.0025mg

Post 0 updates start here    My tapering program     My Intro (goes to tapering graph)

 VIDEO:   Antidepressant Withdrawal Syndrome and its Management

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  • Moderator Emeritus

VIDEO CLIP:  Mark Horowitz explaining SERT occupancy   (the whole video is worth watching)

 

This has been added to Post #1 of this topic.

* NO LONGER ACTIVE on SA *

MISSION ACCOMPLISHED:  (6 year taper)      0mg Pristiq  on 13th November 2021

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 from Oct 2015 - 13 Nov 2021   LAST DOSE 0.0025mg

Post 0 updates start here    My tapering program     My Intro (goes to tapering graph)

 VIDEO:   Antidepressant Withdrawal Syndrome and its Management

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  • 4 months later...

Basically, does it mean it should be easy to taper down from 60 mg Cymbalta to 20 mg, and then one should taper really slowly? Or maybe I don't understand the chart.

2005-2006 : fluoxetine; 2006-2013 : citalopram 20 mg; 2013 : stopped citalopram CT. Total Hell for a year; 2014-2016 : citalopram 20 mg; 2017-2020 : citalopram 30 mg; 2020 : escitalopram 15 mg; 2020 : sertraline 50, then 100 mg; 2020-2022 : duloxetine 60 mg; 2020-2022 : amitriptyline 10-20 mg. Fast taper July-Aug. 2022 from 10-20 (alternating) to 0 in 4 weeks; 2021-2022 : mirtazapine 5 mg (when insomnia, not every day). CT in August 2022.

December 2022: using the brassmonkey tapering method, I am now at 45.5 mg duloxetine and 4.4 mg amitriptyline. Everything is working fine. Magnesium, D3 and omega-3 do help.

April 2023 : 31.9 mg duloxetine and 3.0 mg amitriptyline. Added l-tryptophan, 5-htp and l-tyrosine, and mood is so good I will try 5% tapering (instead of 2.5%) until August (I usually feel better in the summer).

January 2024: 12.0 mg duloxetine and 1.1 mg amitriptyline. Went down 5% weekly (4 weeks / 2 weeks off) all summer, but went back to 2.5% since October. Not always easy, but it goes smoothly. Exercise and good diet makes a big difference to me.

 

 

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  • Moderator Emeritus

SA's suggested taper is no more than 10% of the current dose (not the starting dose), with at least a 4 week hold to allow the brain to adapt to not getting as much of the drug.

 

It is important to listen to your body/symptoms and not make another reduction unless you are stable.

 

Some member need to taper by less than 10% right from the start of their taper, some find that part way through their taper they need to reduce the taper rate.  It is very individual.  What SA does is provide a guide, a starting point; it is not a rule to follow.

 

I have seen members here at SA who have tried to taper faster and it has ended up taking them longer to get off their drug/s than if they had done a nice and careful taper.  Some have ended up on an additional drug, which then needs to be taper, and some have ended up changing to a different drug which does not always work because you can get withdrawal from the first drug and/or side effects/bad reaction to the second drug and because of the variables it can be hard to know what is causing what.

 

Also it is important to note that the effect of taking psychiatric drugs on the nervous system is cumulative.  There are SA members who have stated that they had no trouble in the past changing their doses and/or drugs on numerous occasions and then one day they try to do something that had worked previously but this time it doesn't.

* NO LONGER ACTIVE on SA *

MISSION ACCOMPLISHED:  (6 year taper)      0mg Pristiq  on 13th November 2021

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 from Oct 2015 - 13 Nov 2021   LAST DOSE 0.0025mg

Post 0 updates start here    My tapering program     My Intro (goes to tapering graph)

 VIDEO:   Antidepressant Withdrawal Syndrome and its Management

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I've just got down to 25mg of clomipramine 8 weeks ago... seeing this chart shocks me.. 25mg is the minimum tablet size I can get in Australia... and at 10mg 80% of the sert is still occupied...

 

It almost makes me feel like an idiot.. I've been tapering for years now... I got a long way to go yet 😕

Escitalopram:10mg 2010 - 2014 switched to - Fluvoxamine:300mg 2014-2021 many attempts at tapering, finally off Olanzapine:5mg June 2020

2.5mg, 2mg, 1.5mg, 1mg, .75mg, .5mg, .25mg, 0mg June 2021 Clomipramine 75mg 2020 Dec 50mg 2021 mar37.5mg 2022 june 25mg 2022 Aug 18mg 2022 oct15mg 2022 nov 12.5mg 2023 Jan

9mg 2023 Feb 7.5mg 2023 mar

 

 

 

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  • 7 months later...

Would anyone be able to help me figure out what the occupancy is for fluoxetine (prozac) at the low doses? In other words, show me how to use the equations so I can plug in my dosage and estimate the occupancy? Because it's such a steep drop at the end I'd like to understand how drastic each cut is...I realize it's an estimate but I think it would give me a little peace of mind.

 

Edit - I found it from deeper in the thread...so never mind :)

Zoloft 100mg - June 2015-April 2018 - 2 month taper, had extreme antsiness (different from my normal anxiety) previously said 25mg, was wrong

Xanax 0.25-0.5mg - Aug 2018- Dec 2020 - Rarely took, probably less than every other month. Over 2020 holidays took 0.5mg 5-6times

Escitalopram 10mg - Aug 2018 - Nov 2020 - tapered over 5 months:

June 25 2020 - Aug 14 2020 - Can't remember what I did but assuming it was 5mg this whole time.

Aug 14 2020 - Oct 24th 2020?? - 2.5mg for awhile, then every 27 hrs. Kept trying to extend length of hrs, up to 36. This is where symptoms got bad but I was able to tolerate as it was more fatigue and irritability.

Oct 25 2020 - mid Nov 2020 - 1.25mg every 24-36 hours, then ct. These are estimates because I was cutting the pills and this is 1/8 of 10mg but by now, it was dust. Tried just having the dust toward the end.

Dec 27 2020 major crying spells and depressive, empty/hopeless feeling dead thoughts. Had a couple ok days, a couple really bad ones a week out.

Reinstated liquid Escitalopram 0.15mg - Jan 12 2021  -  Mar 5 2021 - 0.14mg. Mar 16 2021 - 2.5mg. Mar 17 2021 - 5mg. May 21 2021 - 4.8mg. May 28 2021 4.6mg. Jun 9 2021 4.5mg. Jul 7 4mg. Aug 7 2021 3.6mg. Sep 7 2021 3.2mg. Oct 7 2021 2.8mg. Nov 5 2021 2.45mg. Dec 6 2021 2.2mg. Jan 22 2022 2mg. Feb 13 2022 1.9mg. Mar 2 2022 1.8mg. Mar 18 2022 1.7mg. Apr 5 2022 1.6mg. Apr 22 2022 1.5mg. May 13 2022 1.34mg. Jun 16 2022 1.2mg. Jul 16 2022 1.08mg. Aug 13 2022 .97mg. Sep 11 2022 .87mg. Sep 21 2022 .8mg. Sep 27 2022 .7mg. Oct 8 .6mg. Oct 20 .5mg. Nov 1 .4mg. Nov 13 .34mg. Nov 17 .3mg. Nov 24 .24mg. Nov 30 .18mg. Dec 7 .14mg. Dec 8 .12mg. Dec .1mg. Dec 19 .06mg. Dec 24 .02mg. Dec 31 0mg!!

Fluoxetine bridge - Mar 31 2021 - 10mg. Still on this

Reinstated BC (Nuvaring) - Feb 21 2021. 

 

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  • 3 months later...

Does SERT occupancy mean the % of the brain that’s being affected by the drug? If so, then your WD symptoms should be improving greatly as you get lower, and that’s not usually what we see here, right? It hasn’t been the case for me.

 

For example, I recently tried to updose from .06 to .07mg, and I felt the same as I did in college when reinstating from 0 to 10mg, but according to this chart, only 5-10% of my brain is being affected at these low doses. Maybe I’m not understanding. 🤪

May 2019 started lexapro 2.5 mg; 2020 went to every other day; 2021 beginning of Mar, tried to stop but had insomnia; Mar 30, 2021 reinstated 1.25 ev other day, WD symptoms, not enough

April 19, 2021 started liquid, .85 mg/day; May 1, 2021 .8 mg, May 6 .75 mg; June 6 .7 mg, June 20 .65mg, June 30  .6mg, Jul 24 .55 mg, Oct 17 .5 mg, Dec 5- .45 mg; Jan 26, 2022- 4mg,  April 18- .375 ; April 24- .35; April 29- .3; Jun 12- .25 mg; Jun 28- .2 lex; Sept- .15 mg, Nov .1- long hold, never got better

June ‘23- PPPD started 🙁, Jun- .09, Jul- .08, Oct- .07, Dec- .06, Jan ‘24- .05! 
Played around with my dose since Feb & became very unstable w/ extreme acute WD symptoms. Holding @ .06 since May 13.

Taking Magnesium, melatonin, & electrolytes 

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  • 2 weeks later...
On 4/12/2024 at 1:14 PM, Dee12h said:

Does SERT occupancy mean the % of the brain that’s being affected by the drug? If so, then your WD symptoms should be improving greatly as you get lower, and that’s not usually what we see here, right? It hasn’t been the case for me.

 

For example, I recently tried to updose from .06 to .07mg, and I felt the same as I did in college when reinstating from 0 to 10mg, but according to this chart, only 5-10% of my brain is being affected at these low doses. Maybe I’m not understanding. 🤪

Anybody?

May 2019 started lexapro 2.5 mg; 2020 went to every other day; 2021 beginning of Mar, tried to stop but had insomnia; Mar 30, 2021 reinstated 1.25 ev other day, WD symptoms, not enough

April 19, 2021 started liquid, .85 mg/day; May 1, 2021 .8 mg, May 6 .75 mg; June 6 .7 mg, June 20 .65mg, June 30  .6mg, Jul 24 .55 mg, Oct 17 .5 mg, Dec 5- .45 mg; Jan 26, 2022- 4mg,  April 18- .375 ; April 24- .35; April 29- .3; Jun 12- .25 mg; Jun 28- .2 lex; Sept- .15 mg, Nov .1- long hold, never got better

June ‘23- PPPD started 🙁, Jun- .09, Jul- .08, Oct- .07, Dec- .06, Jan ‘24- .05! 
Played around with my dose since Feb & became very unstable w/ extreme acute WD symptoms. Holding @ .06 since May 13.

Taking Magnesium, melatonin, & electrolytes 

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