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

[MarkDavid]

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 December 15, 2021 by MarkDavid
Add an idea. Ask for support

[Mirtazapain]

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.

[ChessieCat]

 

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.

 

.

[ChessieCat]

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

 

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

[bastringue]

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.

[ChessieCat]

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.

[Mogiebear]

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 😕

[tryingtosurvive330]

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

[Dee12h]

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. 🤪