Martin aka paused||M.E.
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My ATP is absolutely fine (tested in three labs) and Abilify took me from very very severe to almost moderate
Abilify- Stanford Clinic Patients
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I'm not saying not trying both, I'm just saying there's no info to go by and that is my critique of that person's post. Really annoys me when people write they've been doing so much research yet don't seem to share any of it with us, thanks to this person (but no thanks)!
Maybe ME metabolic dysfunction only affects certain cell types i.e. in the brain, or liver, etc. So not covered by ATP measurements you did of peripheral cells.
This isn't what people have reported, if anything for many people where it works 2 mg is too high and seems overall that 1 mg is the "sweet spot". But yes for some 2 mg is best but others not, so just be careful you might overshoot and and then you are just increasing risk of side effects without beneficial effects.
so then I'll stay at 1mg for few months to evaluate improvements, then increase to 2mg to see if bigger dose gives more improvement?
Martin aka paused||M.E.
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My contact at Stanford (staff of Ron's team) doesn't think it has sth to do with ATP... Our weakness I mean
I'll let others chime in here too, but from my summary of all the other anecdotes in general 1 mg seemed like a sweet spot but it depends on the individual. But I've read many times people go higher than their individual sweet spot and the drug doesn't work any better than at lower dosage, only increases in side effect risk.
Then what is their theory as to why Abilify works? I mean they are spending all this effort on the metabolic trap which unless I'm mistaken effectively causes similar cellular metabolism issues to what I've quickly described in the theory above.
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From my experience with Abilify you won't need months to evaluate at a specific dosage the improvements you've experienced and where it will plateau. Takes 2 months max at a specific dose.
Martin aka paused||M.E.
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I didn't ask her... Last talk is half a year ago
Like this to me is conflicting data
Amisulpride: a review of its use in the management of schizophrenia
It’s doing the same thing here as Abilify so why would it prevent any tolerance if as people are suspecting the tolerance is driven by dopamine autoreceptors? Seems like you would just get cross-tolerance.
Unless dopamine autoreceptors have nothing to do with poop out in ME.
Amisulpride: a review of its use in the management of schizophrenia
It’s doing the same thing here as Abilify so why would it prevent any tolerance if as people are suspecting the tolerance is driven by dopamine autoreceptors? Seems like you would just get cross-tolerance.
Unless dopamine autoreceptors have nothing to do with poop out in ME.
sb4
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@leokitten I'm having trouble understanding your idea on how abilify works. As far as I understand it, you are saying that dopamine is very costly energetically to the brain so abilify has the dopamine hang around longer. It does this by blocking presynaptic autorecepters?
I thought blocking these would just lead to more dopamine release requiring more energy but that aside. Why couldn't the body just do what abilify does, as in let the dopamine hang around longer. It has to be keeping dopamine low deliberately and the medication bypasses what the brain wants to do but it leads to symptomatic improvement regardless. IDK.
I thought blocking these would just lead to more dopamine release requiring more energy but that aside. Why couldn't the body just do what abilify does, as in let the dopamine hang around longer. It has to be keeping dopamine low deliberately and the medication bypasses what the brain wants to do but it leads to symptomatic improvement regardless. IDK.
Remember too that the aripipirazole molecule itself is like a partial dopamine molecule and has instrinsic activity and binding affinities between 15-90% of endogenous dopamine depending on dopamine receptor type and brain area. So it’s not only affecting the flow of dopamine in synapses etc and where but it itself functions as a neurotransmitter.
Running the dopamine system of the brain appears to be an energy intensive process compared to other neurotransmitter systems and it’s has to create dopamine and put into vmat2 vesicles near ends of neurons, unpackage dopamine and push into the synapse, bind to pre and post synaptic receptors, perform neurotransmission, collect dopamine back into neuron, package into vmat2 or mao oxidize, etc etc very frequently compared to other neurotransmitter systems (it’s controlling all fine and gross muscle movements, arousal and desire, reward, etc, you get my drift your dopamine system is at the very center of what we are)
I think you are just looking at the synaptic neurotransmission part, but I’m guessing at some other points in the entire cycle reduced ATP and/or increased ROS generation due to cellular metabolism and mitochondrial dysfunction can driving overall dopamine system dysfunction too.
For example reduced ATP generation and increased ROS generation due to dysfunction of mitochondrial complex I is implicated in Parkinson’s disease.
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I’m not sure the brain is doing any kind of down-regulation as a reaction, it just cannot keep up with the required dopamine system demands to not have many neurological ME symptoms. I do not think the dopamine system can run at a lower state without issues, and I think in ME given some symptoms it’s not necessarily running at a lower state it’s more erratic (light and sound sensitivity, cognitive overload, etc)
I also think it’s not just about increased dopamine with Abilify and ME, it could also be the system stabilization aspect that is very helpful at mitigating symptoms here too?
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One fact I was wondering about, neurons preferentially metabolize glucose and generate energy via the pentose phosphate pathway (PPP) instead of glycolysis in order to retain their antioxidant status, is there some research regarding ME and disturbances in the PPP?
Interesting piece about dopamine reservoirs and receptors outside the brain.
The Effects of Dopamine and Antipsychotic Drugs on the Body’s Ability to Respond to Insulin
Maybe, just maybe, Abilify’s positive effect on ME has nothing to do with dopamine-serotonin system stabilization in the brain but some counterintuitive positive effect it has on ME metabolic dysfunction.
The Effects of Dopamine and Antipsychotic Drugs on the Body’s Ability to Respond to Insulin
Maybe, just maybe, Abilify’s positive effect on ME has nothing to do with dopamine-serotonin system stabilization in the brain but some counterintuitive positive effect it has on ME metabolic dysfunction.
Martin aka paused||M.E.
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Hmaybe. But why then the tolerance? And why does this tolerance also occur if you don’t take it low dose for ME but for depression
But I thought it what was unique about Abilify tolerance in ME is that it happens so fast (3-4 months).
If Abilify stopped working in 3-4 months for current FDA approved conditions the drug would be done for, no clinician would prescribe it. I believe similar to antidepressants and other psychotropic meds, Abilify tolerance can develop in some people much more slowly for depression or other FDA approved conditions (taking years to develop).
Martin aka paused||M.E.
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I don’t think that tolerance occurs in so many. I think we are around the 1-5% of poor souls. And the German guy also says that it occurs in some after weeks
Wait so poop out in ME anecdotally is as low at 5% in pwME who trial Abilify? Sorry I thought it was much, much higher.