Abilify tolerance

pattismith

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hmnr asg

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but he suggested Rexulti. So I’m going off Abilify and starting that soon. All my doctors said that the half life of Abilify is so long you don’t need to taper it. But that doesn’t invalidate your withdrawal symptoms.

Hey Whit,
How did rexulti end up working ?
 

leokitten

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@leokitten how are you doing? Is your second chance with Abilify still working? (I hope so:angel:)

My second cycle was still helpful until Nov 2022 when I had to stop. Didnt get to do a third cycle until this past March and it worked again though something different this time I had to take 2 mg per day instead of 0.5 and the effects came on in a more slow and smooth fashion compared to the first two cycles. Even though it came on slower it worked amazingly though I was able to go on a vacation for the first time in 3 years. But unfortunately this time LDA only worked for a little over a month before my ME symptoms came back in full. The need for a higher dose, the slower initial response, and the shorter response period all of this I still don’t understand maybe because I’m taking Prozac as well now.
 
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leokitten

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Let’s bring this thread back to life

Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone, Stove et al, 2022

In addition to ziprasidone there are other generic drugs people could try to inhibit VMAT2 for a while and possibly reverse Abilify tolerance.

OMG I didn’t know fluoxetine is a known and pretty strong VMAT2 inhibitor! Ok wow maybe this is a theory as to why LDA didn’t work as long this third cycle
 
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Why do you view VMAT2 inhibition as a goal? VMAT2 inhibitors like reserpine deplete dopamine pools, and are commonly used to induce fibromyalgia- and fatigue-like states in lab animals.
 

leokitten

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Why do you view VMAT2 inhibition as a goal? VMAT2 inhibitors like reserpine deplete dopamine pools, and are commonly used to induce fibromyalgia- and fatigue-like states in lab animals.

I’m asking @jaybee00 the same question I think it’s in the other Abilify thread. He posted that valbenazine would be an idea to reverse Abilify tolerance in ME.
 

leokitten

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A Method to Reverse Abilify Tolerance

The problem with this idea is the user doesn't explain what is the basis for his theory as to why it would work.

Amisulpride is a D2/3 and 5-HT2B/7 antagonist. It has no efficacy at other receptors. For this reason I think something like ziprasidone, which is a D2/3/4 and 5-HT2A/2B/2C antagonist and 5-HT1A/1B/1D partial agonist, and I believe is a safer antipsychotic to use than amisulpride, would work similarly to reverse tolerance.
 

leokitten

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Amisulpride hits a few serotonin receptors to a degree, table of receptor affinities halfway down this page.
Anything with binding affinity >100 is meaningless and doesn't contribute to efficacy. The only serotonin receptors with significant binding are the two I listed 5-HT2B/7
 

leokitten

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@Hip and others - I might've missed it in this thread, but what is the theory as to why amisulpride would work to reverse Abilify tolerance, other than just one anecdotal report?
 

Hip

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@Hip and others - I might've missed it in this thread, but what is the theory as to why amisulpride would work to reverse Abilify tolerance, other than just one anecdotal report?

I don't what the theory is, but it seems that the German person in the the post that you linked to above had some sort of theory.
 

leokitten

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I'm thinking the theory is that in pwME the initial triggering illness and immune response triggered permanent dopamine dysfunction and particularly hypofunction in at least part of our dopamine network and this is what contributes in a major way to PEM and fatigue.

Abilify is generally a D2 autoreceptor agonist in areas with low dopaminergic tone, and this agonism inhibits presynaptic dopamine synthesis and release. In full detail Abilify is a unique functionally selective agonist or antagonist depending on dosage and local dopaminergic tone. But in general I think that its presynaptic receptor agonism is what's thought to cause us tolerance after a few weeks to months.

Amisulpride is a D2 autoreceptor antagonist at low doses, which promotes presynaptic dopamine synthesis and release and this property is what I believe people think will reverse Abilify tolerance that has built up.
 
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