Abilify- Stanford Clinic Patients

[choochoo]

Well isn't low dopamine a chemical imbalance?

 

[Badpack]

@choochoo and which study implies that cfs patients have low dopamine ?

 

[YippeeKi YOW !!]

But once people start listing, non-objective reasons for it while putting them forward like they are objective reasons then this is fully open to critique.

Open exchange of input and ideas is how hypotheses are constructed, then tested, then matured into actual theses which could definitely help a whole lot of patients in this forum.

Einstein's Theories all evolved pretty much that way, starting with a thought process originating with Einstein, then batted about by Einstein in partnership with other scientists ....

That's pretty much what this forum is for, whether or not we're actual scientists. We're experimenting with the most valuable and irreplaceable thing we have: our lives, so the stakes are pretty high.

 

[stefanosstef]

Let's stop this argument and focus on the drug and Stanford's updates please.It's everyone's responsibility to research any drug he/she takes.Nothing is without risk but I will repeat that the known side effects may very well not apply to such a low dose that in fact works in an opposite way than full dose.

 

[Badpack]

@stefanosstef everyone seems to always say low dose works in an opposite way than full dose. Do you have a study at hand for this ? Would like to read into this some more.

 

[YippeeKi YOW !!]

@stefanosstef everyone seems to always say low dose works in an opposite way than full dose. Do you have a study at hand for this ? Would like to read into this some more.

I'd be interested too.

It's become received wisdom that somehow the off-label use of Abilify for ME at low doses morphs into something else, something healing and much less damaging and dangerous, but I've never been able to pin down any research studies that indicate that in a scientific, as opposed to hypothetical and anecdotal, way.

 

[Rebeccare]

THIS THREAD HAS BEEN RE-OPENED. PLEASE KEEP THE DISCUSSION RESPECTFUL AND ON-TOPIC.

IF YOU SEE ANY VIOLATIONS OF THE FORUM RULES, PLEASE REPORT THOSE POSTS INSTEAD OF RESPONDING TO THEM.

 

[YippeeKi YOW !!]

One significant positive thing about pramipexole (and I believe also with ropinirole) is that there’s significant scientific evidence that it exhibits strong mitochondrial protective effects in the brain.

Could you cite your sources for that significant evidence?

And I thought that any mitochondrial involvement in ME had been negated by either you or another poster in this thread a little ways back.

 

[stefanosstef]

@stefanosstef everyone seems to always say low dose works in an opposite way than full dose. Do you have a study at hand for this ? Would like to read into this some more.

@YippeeKi YOW !!

There are a few studies on this and from what I've read it is widely known and not questioned:

Low-dose systemic aripiprazole (<1 mg/kg) also increased extracellular dopamine levels in the cortex [62, 63]. On the other hand, high-dose systemic aripiprazole (10–40 mg/kg) reduced dopamine levels [64–66]. This biphasic effect may depend on the prevalence of agonistic 5-HT1AR-mediated effects at low doses, and the prevalence of inhibition of mesocortical dopaminergic neurons activity at high doses [65].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602118/

Edit:Actually that is what partial agonism means.Receptor agonism at low doses and antagonism at full doses.

 

[leokitten]

@choochoo and which study implies that cfs patients have low dopamine ?

@Badpack there’s a couple studies, one looking directly as basal ganglia activity in CFS

Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue

And a few other well known studies which found neuroinflammation in CFS in certain areas of the basal ganglia, as well as other areas. Neuroinflammation we discussed will cause neurotransmitter dysfunction in those brain areas.

There is also a recent talk on prepublished work discussed in a thread here by a group at Stanford which did TSO-PET MRI and is yet another group to find neuroinflammation in the basal ganglia.

 

[leokitten]

Could you cite your sources for that significant evidence?

And I thought that any mitochondrial involvement in ME had been negated by either you or another poster in this thread a little ways back.

You took this quote out of context as I was just stating something general about these two drugs regarding mitochondrial neuroprotection, and I followed this quote saying exactly that in ME there isn’t proof that there’s anything up with our mitochondria.

Search PubMed for “pramipexole mitochondria” etc and you will find a number of papers.

 

[andyguitar]

And a few other well known studies which found neuroinflammation in CFS in certain areas of the basal ganglia, as well as other areas. Neuroinflammation we discussed will cause neurotransmitter dysfunction in those brain areas.

So how about using the same scanning techniques on patients in an Abilify trial. Scans before and after a course of treatment?

 

[Badpack]

@stefanosstef thanks. Will look into this some more.

@leokitten decreased activity in these regions doesn't automatically means less dopamine activity though. Otherwise Cfs ppl would show significant symptoms of other diseases with low dopamine in these regions. Like Huntingtons diseases or Parkinson.

 

[leokitten]

@stefanosstef thanks. Will look into this some more.

@leokitten decreased activity in these regions doesn't automatically means less dopamine activity though. Otherwise Cfs ppl would show significant symptoms of other diseases with low dopamine in these regions. Like Huntingtons diseases or Parkinson.

There’s a huge difference between dopamine cell death and that level of dysfunction and simply having lower activity due to local neuroinflammation due to some other cause.

Remember people with PD do not exhibit any motor symptoms until they’ve lost 50-70% of their dopamine neurons in the substantia nigra. That is a devastating loss. But for years prior to that they certainly have other subclinical and non-motor symptoms.

EDIT: even people with treatment-resistant depression have been shown to have lower dopamine activity in the basal ganglia, and its generally agreed upon that depression is a neuroinflammatory disorder.

 

[YippeeKi YOW !!]

Please take into account that the low dose regimen discussed here effectively change antipsychotics into totally different drugs.

In what way, and exactly how. And to what new effect?

This seems to fly in the face of all laws of physics. Would be interested in knowing more, could you cite your sources?

 

[leokitten]

In what way, and exactly how. And to what new effect?

This seems to fly in the face of all laws of physics. Would be interested in knowing more, could you cite your sources?

please read @stefanosstef recent post, we’ve also had similar posts in this thread discussing how partial agonism/functional selectivity works and how low dose changes the effect compared to higher dose.

 

[Badpack]

@leokitten sure, but Cfs ppl even after +20 years of sickness dont show any sign of progression in this way. No dyskinesia or other sign that would show a progression in lowering dopamine over time. So the theory here would be it gets lowered once and then stays there forever ? without any progression or worsening in dopamine levels ever again ? Doesnt sound very plausible to me.

 

[leokitten]

@leokitten sure, but Cfs ppl even after +20 years of sickness dont show any sign of progression in this way. No dyskinesia or other sign that would show a progression in lowering dopamine over time. So the theory here would be it gets lowered once and then stays there forever ? without any progression or worsening in dopamine levels ever again ? Doesnt sound very plausible to me.

Neither do treatment-resistant depressed people. If you don’t have a physiopathology which causes dopamine cell death like PD then you won’t get progression, but if you have a pathology which causes neuroinflammation in the region without cell death then you will have chronic lower activity and symptoms without progression.

 

[YippeeKi YOW !!]

Believe me there is not much to lose on my end at this point.

I truly hope that's not the case .... I know how grim this illness gets, but even that can be turned around, and it could be that Abilify is exactly what will do that for you ....

And maybe at least I can be a data point on this forum for others to use in forming some kind of hypothesis.

I hope more than that. Maybe a shining success story? Yeah, that's the ticket .....

As @stefanosstef said, when things are bad enough, different issues and weights go on the scales ....

 

[YippeeKi YOW !!]

Edit:Actually that is what partial agonism means.Receptor agonism at low doses and antagonism at full doses.

Agreed, and thank you for your very civil post .

There are numerous drugs, if not possibly all of them, that function in different ways at different dosage levels, hence the old axiom, "The dose makes the poison" .....

But it still doesn't support the actual conversion of a known drug into something else entirely, which is the post I was questioning .... throwing around a lot of foggy assertions can be potentially damaging if taken at face value.