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Abilify tolerance

leokitten

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It measures acetones and I’m at above 9 ppm

Maybe keto doesn’t help your ME. I don’t remember exactly but I believe I already felt some minor signs of improvement before getting to deep ketosis.

Ketoscan has strange levels as they have a lot of levels between 0 - 9 ppm but then only one level for 10-40 ppm. They say 10-40 ppm is deep ketosis. Being nearer to 40 though is too much long-term.

https://ketoscan.com/understanding-ketone-status-measurement/

https://www.ketoscanmini.co.uk/ketosis-levels/

Not making any medical advice but if I were at 9 ppm not sure if worthwhile to try and go somewhat higher to see if ME symptoms would significantly improve after being at that level for a little while. I think main advantage is if it still doesn’t work at higher ppm then I would know with confidence keto doesn’t work for me.
 
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leokitten

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I was searching through PR and a few people had discovered Abilify’s efficacy in ME as far back as 2012, and within this thread there’s a couple interesting posts from 2017 where a user detailed her experiences with Abilify and, like others have found recently, efficacy lasting her ~4 months before it stopped working.

But she learned that by pausing for about 4-6 months after it stopped working she could then start it again and it would work again on average for ~4 months. If she paused for a shorter time it wouldn’t work, which is in line with what others have reported recently here.

It looks like she did this cycle multiple times and it worked each time. On one cycle it even worked for 7 months, which she attributed to also taking antivirals.

Anyway, read here:

https://forums.phoenixrising.me/threads/abilify-and-energy.20815/#post-832373

https://forums.phoenixrising.me/threads/abilify-and-energy.20815/#post-832384

I know it’s only an anecdote of n=1, but I hope it gives people here some optimism that maybe for some there isn’t a permanent tolerance like we see with other treatments.
 
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Hi guys, as usual, I'm posting this question for my friend Frank who is too sick to be on this forums in general. He's been taking abilify for over 4 months but now he's considering switching to Amisulpride (a very low dose of course) to see if he can get similiar results. Is there anyone here who's made this switch? If so, did you stop Abilify completely before starting Amisulpride or did you cross-taper? I would appreciate any recommendations or anecdotes.
Thanks! :)
 

Hip

Senior Member
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If so, did you stop Abilify completely before starting Amisulpride or did you cross-taper?

Abilify has a half life of 3 days, so leaves the body slowly. But say 10 after stopping this drug, most of it will have left the body. At that point I would think you could start very low-dose amisulpride. I take just 12.5 mg of amisulpride daily.

You could consider cross-tapering though at an earlier point.
 

leokitten

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Hi guys, as usual, I'm posting this question for my friend Frank who is too sick to be on this forums in general. He's been taking abilify for over 4 months but now he's considering switching to Amisulpride (a very low dose of course) to see if he can get similiar results. Is there anyone here who's made this switch? If so, did you stop Abilify completely before starting Amisulpride or did you cross-taper? I would appreciate any recommendations or anecdotes.
Thanks! :)

May I ask why wanting to change? Aripiprazole and amisulpride are actually not as similar pharmacologically as people might initially think.

They have quite different affinities and intrinsic activities at serotonin receptors and aripiprazole is a stronger functionally selective partial agonist at dopamine receptors. In fact, amisulpride has quite weak or nonexistent function at serotonin receptors.

If you look up and compare their pharmacologies you will see. For an easy to see overview, I posted a document about brilaroxazine on this post which has an overview of antipsychotics too

https://forums.phoenixrising.me/threads/abilify-stanford-clinic-patients.62807/page-45#post-2324013

Here’s the doc link again below. Look at the table “Exhibit II – Receptor Pharmacology of Antipsychotics”

https://s1.q4cdn.com/460208960/files/News/2021/Zacks_SCR_Research_01132021_RVPH_Vandermosten.pdf

Aripiprazole is really quite different from amisulpride.
 

leokitten

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Switching to amisulpride, whether it works or not, will help identify which receptors are involved in the therapeutic benefits of Abilify.

To be frank I believe it’s likely to either not be true or be a poor way to figure things out. We have no idea how or why Abilify works. It might not be receptor affinities at all, or it could be a complex interplay of receptor interactions.

As I wrote before in this post https://forums.phoenixrising.me/threads/abilify-stanford-clinic-patients.62807/page-44#post-2321719
1. Dopamine-serotonin system stabilizer
2. Anti-neuroinflammatory
3. Positively effects ME cellular metabolism dysfunction
4. Positively effects possible ME hypothalamus and pituitary gland dysfunction

As you can tell these hypotheses are overlapping and it could be all of these.

Changing to amisulpride will barely give even any answers to 1. let alone tell us nothing about the rest.
 
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leokitten

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Also, I know there aren’t many amisulpride reports at all, but even @Hip your experience on how much it improved your symptoms were to me a lot less compelling than what I’ve read about peoples’ experiences with Abilify? I could be wrong but I never read from your posts that it has such an amazing effect like Abilify has had on so many people.
 

Hip

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To be frank I believe it’s likely to either not be true or be a poor way to figure things out. We have no idea how or why Abilify works. It might not be receptor affinities at all, or it could be a complex interplay of receptor interactions.

It may not yield any answers, sure, but it's very simple to get hold of some amisulpride and try it, so why not?

For all we know, amisulpride might work better than Abilify. And if amisulpride does work, it might not peter out like Abilify does for some. There is no harm in experimenting.



Also, I know there aren’t many amisulpride reports at all, but even @Hip your experience on how much it improved your symptoms were to me a lot less compelling than what I’ve read about peoples’ experiences with Abilify? I could be wrong but I never read from your posts that it has such an amazing effect like Abilify has had on so many people.

The benefits I got from very low-dose amisulpride are not as major as some of the benefits reported with Abilify.

However, I might be a non-responder to Abilify, and if so, my results with amisulpride would not tell us much. We really need someone who is a known major responder to Abilify to test amisulpride, and preferably test it before the benefits of Abilify peter out for them.



I might also be using too low a dose of amisulpride. The dose equivalence is: amisulpride 38.3 mg/d = aripiprazole 1.4 mg/d. Ref: here.

Some people are taking 2 mg of Abilify daily, so that would be equivalent to 55 mg of amisulpride daily. I have only taken doses up to 25 mg of amisulpride daily on a regular basis, so I have not really explored the full dose range.

I find 50 mg doses of amisulpride tend to numb or tranquilize my mind slightly, and make me less motivated, and so I have not tried 50 mg for more than a day or two. Also, with the serious side effects of antipsychotics, I think it is best to take the lowest dose possible.
 

pattismith

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Switching to amisulpride, whether it works or not, will help identify which receptors are involved in the therapeutic benefits of Abilify.
Why not starting with methylphenidate, the stimulant used on Narcolepsy and ADHD?
it works quickly and a few days trial is enough to test if brain Dopamine level (or norepinephrine to a lesser extent) is involved.

"It binds to the dopamine (DA) transporter (DAT) and norepinephrine (NE) transporter and blocks neurotransmitter reuptake ), thereby increasing their extracellular levels"
 

leokitten

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It may not yield any answers, sure, but it's very simple to get hold of some amisulpride and try it, so why not?

For all we know, amisulpride might work better than Abilify. And if amisulpride does work, it might not peter out like Abilify does for some. There is no harm in experimenting.

One major reason is because @Sele Frank is severe ME. Sorry that I got a little tiffed @Hip (please accept my apologies). I also asked myself why in all this time haven't you experimented with Abilify to test the same thing you are recommending?
 

leokitten

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Why not starting with methylphenidate, the stimulant used on Narcolepsy and ADHD?
it works quickly and a few days trial is enough to test if brain Dopamine level (or norepinephrine to a lesser extent) is involved.

"It binds to the dopamine (DA) transporter (DAT) and norepinephrine (NE) transporter and blocks neurotransmitter reuptake ), thereby increasing their extracellular levels"

I think we can all say with fairly good certainty, because so many here have trialed stimulants for ME over the years, and all different kinds of stimulants (releasers, reuptake inhibitors, etc), that the reason Abilify works is not because it's simply boosting dopamine or acting as a dopamine agonist in place of low dopamine.

Stimulants didn't make my ME symptoms go away or reduce at all, it just allowed me to ignore them more (even though I felt them right there with me) until I crashed hard. Abilify feels completely different actually improves ME symptoms substantially, including the worst and hardest to treat of them all, PEM.
 

Hip

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I also asked myself why in all this time haven't you experimented with Abilify to test the same thing you are recommending?

I tried Abilify in place of amisulpride about 8 years ago just out of curiosity, and also more recently a few month back as a result of all the current interest in Abilify. Unfortunately on both occasions I got an unpleasant overstimulation effect from Abilify, which I do not get from amisulpride.

Because of the long half life, just one dose of Abilify causes this overstimulation to last the for much of the week. It's then a relief when the Abilify finally wears off, and I can go back to a relatively relaxed mental state.

I expect this overstimulation comes from the adrenergic receptor agonism of Abilify. If I could find a workaround (to block the adrenergic receptors), then I could try Abilify, which I would very much like to do. Of course, it could be that the adrenergic agonism is part of the therapeutic effect of Abilify, and so if I block that, it might prevent Abilify from working.



Why not starting with methylphenidate, the stimulant used on Narcolepsy and ADHD?
it works quickly and a few days trial is enough to test if brain Dopamine level (or norepinephrine to a lesser extent) is involved.

It may not be dopamine levels per se which are the issue in ME/CFS. Abilify and amisulpride are dopamine stabilizers, which means they reduce dopamine receptor agonism when the dopamine signal is strong, but increase receptor agonism when the dopamine signal is weak.

Abilify and amisulpride are analogous to a musical compressor effects pedal (often used by guitarists), which boosts the volume of musical notes played softly, but reduces the volume of notes played loudly. A compressor thus reduces the dynamic range of the music. Likewise, Abilify and amisulpride reduce the dynamic range of the dopamine signal.

You cannot mimic the dopamine stabilizing effects of Abilify and amisulpride with just simple dopamine agonists or antagonists.
 

leokitten

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I expect this overstimulation comes from the adrenergic receptor agonism of Abilify. If I could find a workaround (to block the adrenergic receptors), then I could try Abilify, which I would very much like to do. Of course, it could be that the adrenergic agonism is part of the therapeutic effect of Abilify, and so if I block that, it might prevent Abilify from working.

Abilify is very likely an antagonist at adrenergic receptors, like all antipsychotics are if they have any affinity for those receptors. See Exhibit II here https://s1.q4cdn.com/460208960/files/News/2021/Zacks_SCR_Research_01132021_RVPH_Vandermosten.pdf

So if Abilify is stimulating you it’s likely the higher intrinsic activity at dopamine receptors or it’s varied functions at serotonin receptors, which amisulpride has very little of.

But even if Abilify stimulated you more than you wanted, did it work? If it stimulated me too much I would try only taking 0.1 mg.
 
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Hip

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In terms of why reducing the dynamic range of the dopamine signal might be helpful, it could be that the gain or amplification on dopaminergic neurons is set too high in ME/CFS, so that the dopamine signal is over-amplified by these neurons.

Too high a gain might possibly result in further issues, like dopamine receptor downregulation, which in effect is a compensatory way of reducing the gain or amplification of the dopamine signal.

I believe that the gain control ("volume control") on a neuron is set by the neurotransmitter glutamate. The more glutamate, the more the neuron will amplify incoming signals.

Some researchers have speculated that glutamate levels are high in the brains of ME/CFS patients (and speculate this is the cause of the "wired" feeling in ME/CFS). If there is high glutamate, it would explain why the gain control on neurons is turned up to maximum. Copious amounts of glutamate are produced by microglia during brain inflammation, so if there is a chronic viral brain infection in ME/CFS, then that would explain the high glutamate.

So Abilify may be just compensating for an excessively high gain control setting on dopamine neurons. This drug will dampen any strong dopamine signals input to the neuron, so that the signal does not get over-amplified. But at the same time, it allows weaker dopamine signals to get through.
 
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YippeeKi YOW !!

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Second star to the right ...
Abilify and amisulpride are analogous to a musical compressor effects pedal (often used by guitarists), which boosts the volume of musical notes played softly, but reduces the volume of notes played loudly. A compressor thus reduces the dynamic range of the music. Likewise, Abilify and amisulpride reduce the dynamic range of the dopamine signal.
This is probably the best description of the mode of action of antipsychotics, particularly, that I've read so far :trophy::trophy::trophy:....
 

Hip

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Abilify is an very likely an antagonist at adrenergic receptors, like all antipsychotics are if they have any affinity for those receptors. See Exhibit II here

What do the +++ symbols represent in that Exhibit II table, the receptor binding affinity? That will not tell you whether Abilify acts as an agonist or antagonist.

Generally the feeling of stimulation can come from adrenergic receptor agonism, from adenosine receptor antagonism, and I suspect the similar feeling of being "wired" may come from too much glutamate. So there is more than one mechanism which can cause overstimulation.



But even if Abilify stimulated you more than you wanted, did it work? If it stimulated me too much I would try only taking 0.1 mg.

I got this overstimulation effect even from a single 0.1 mg dose of Abilify.

My ME/CFS started after a viral brain infection in 2005, which cause some mild brain damage, leaving me with ADHD, and prone to getting the mental tension symptom of generalized anxiety disorder, which is similar in some ways to the "wired" overstimulation feeling of ME/CFS. So this could be why I have trouble tolerating Abilify.