Abilify- Stanford Clinic Patients

[leokitten]

With antipsychotics more isn’t better. For example low doses of aripiprazole actually produce a different and more dopamine activating and stabilizing effect compared to higher doses, which are dopamine blocking. This is why very low doses helped at least temporarily many people with ME, but higher doses didn’t work or didn’t work any better and just produced more side effects. This is a property of partial agonists that depending on their IA at a receptor will behave differently at low vs high doses. Wrt cariprazine since at D3 it has 70% IA, then for sure it’s more activating at D3 at LOW doses but more D3 blocking at higher doses.

If you don’t have psychosis and want the reduce side effects you might not want to take such a high dose.

 

[SlamDancin]

Well, first of all to answer your question, it’s not exactly by choice. In order to not derail the thread, I won’t get into specifics, but the people that are responsible for my financial support, and a team of psychiatrists they contracted, believe it’s possible that I may be having psychosis. I’m not, but they cannot be convinced otherwise at least at this point. Secondly, as I posted before, with the D3 receptor it appears as if antagonism may be activating versus agonizing the receptor. So, fingers crossed.

 

[leokitten]

Well, first of all to answer your question, it’s not exactly by choice. In order to not derail the thread, I won’t get into specifics, but the people that are responsible for my financial support, and a team of psychiatrists they contracted, believe it’s possible that I may be having psychosis. I’m not, but they cannot be convinced otherwise at least at this point. Secondly, as I posted before, with the D3 receptor it appears as if antagonism may be activating versus agonizing the receptor. So, fingers crossed.

Do you get PEM after physical and/or mental exertion? What is your severity level?

 

[SlamDancin]

I think I’m an interesting case as I seem to be one of those with a physical root cause. PT exercises given to me by a sports medicine doctor after taking X-rays a few years back have improved my baseline significantly.

I was very severe, spending most days in bed. Over the last five years or so I’ve improved my
Baseline to mild levels. Unfortunately, my exercise intolerance is still very strong, for example if I walk just a little too much in a day I can trigger PEM. The PEM Is still relatively strong, so it knocks me out with the same ferocity as before, but because my baseline is much improved it’s not as terrible.

I just saw a neuromuscular specialist who tested for neuropathy/myopathy/dystrophy and ruled them all out. He referred me to the PT clinic and, frustratingly but possibly correct, said that with PT I will possibly be able to overcome PEM.

And yes, certain things like especially mentally stressful/emotional days can also trigger PEM for me, although it’s slightly different from physically triggering PEM

 

[leokitten]

If Vraylar is going to work you will notice it within the next week or so. If I’m not mistaken for virtually everyone who had a significant response to these drugs it takes only a couple weeks. For me on my first trial in 2021 it took two weeks of feeling nothing and then bam the ME symptoms just melted away. I cannot explain why but the two cycles after that it started working after one week.

 

[hmnr asg]

I was just started on 1.5mg Vraylar (Cariprazine) for non-CFS reasons. As you may know it’s much stronger at the D3 dopamine receptor relative to D2 than Abilify. How long have you been taking it and what dose? Glad to know it’s helping you and not hurting. I had the weirdest insomnia last night where I fell asleep only to wake up shortly after all throughout the night. Have you noticed any insomnia?

Im taking 1.5 which is the minimum dose, and since its a capsule its a pain to try to take a lower dose. But i guess since it has such a long half life i could take it every other day or maybe every 2 days. I virtually had no side effects.

With antipsychotics more isn’t better.

Do we know this to be a fact from actual people's experience? I know the original paper from Stanford argued this but I don't trust that Bonilla quack. Imagine if higher doses would also work and it would help the people who have pooped out. I guess my question is, is your statement coming from the paper and is based on theory or from actual CFS peoples' experience?
ps long time no chat and hope youre well!

 

[leokitten]

Im taking 1.5 which is the minimum dose, and since its a capsule its a pain to try to take a lower dose. But i guess since it has such a long half life i could take it every other day or maybe every 2 days. I virtually had no side effects.


Do we know this to be a fact from actual people's experience? I know the original paper from Stanford argued this but I don't trust that Bonilla quack. Imagine if higher doses would also work and it would help the people who have pooped out. I guess my question is, is your statement coming from the paper and is based on theory or from actual CFS peoples' experience?
ps long time no chat and hope youre well!

Evidence for this is from the many anecdotal reports from pwME, including my own experience experimenting with Abilify, that going to 5 or 10 mg a day did nothing for efficacy and only brought on a lot of side effects. I never saw a report from anyone saying >2-4 mg per day had better efficacy.

 

[leokitten]

Im taking 1.5 which is the minimum dose, and since its a capsule its a pain to try to take a lower dose. But i guess since it has such a long half life i could take it every other day or maybe every 2 days. I virtually had no side effects.


Do we know this to be a fact from actual people's experience? I know the original paper from Stanford argued this but I don't trust that Bonilla quack. Imagine if higher doses would also work and it would help the people who have pooped out. I guess my question is, is your statement coming from the paper and is based on theory or from actual CFS peoples' experience?
ps long time no chat and hope youre well!

Sorry I just remembered there is more evidence. In the various human radioligand PET occupancy studies on the dopamine partial agonists (3rd gen) antipsychotics, Abilify being the prototypical one, they all showed that they will already occupy a lot of our dopamine receptors at dosages much lower than the schizophrenia or bipolar dosage ranges. Already at 2mg per day aripiprazole occupies 72% of D2 receptors. Here’s the latest and I think best of the aripirpazole PET studies:

Kegeles LS et al. Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride. Neuropsychopharmacology. 2008 Dec;33(13):3111-25.

So if we use one of the prevailing theories of ME that parts of our immune system are stuck in a chronic inflammatory and dysfunctional state and this has deleterious neurological and cellular metabolic consequences, and one likely consequence being that our dopamine and serotonin CNS systems are dysfunctional causing a lot of our symptoms, and that low dose Abilify comes is able to partially correct some of this for a time, then there’s no reason to go to higher doses because we mostly need the agonist and stabilizing effects of Abilify not the blocking effects at higher dosages.

 

[leokitten]

Im taking 1.5 which is the minimum dose, and since its a capsule its a pain to try to take a lower dose. But i guess since it has such a long half life i could take it every other day or maybe every 2 days. I virtually had no side effects.


Do we know this to be a fact from actual people's experience? I know the original paper from Stanford argued this but I don't trust that Bonilla quack. Imagine if higher doses would also work and it would help the people who have pooped out. I guess my question is, is your statement coming from the paper and is based on theory or from actual CFS peoples' experience?
ps long time no chat and hope youre well!

How was your experience with Rexulti? Based on hundreds of anecdotal reviews on drugs.com Rexulti seems to get the best overall users reviews compared to Abilify and Vraylar. Did you find Rexulti less activating than Abilify?

 

[SlamDancin]

Well I had to stop Cariprazine after just five doses as I was getting the same sleep myoclonus that Abilify was giving me. It prevents me from being able to sleep and it’s hellish, having tremors right as I am falling asleep over and over all night. After around 36 hours post last dose I was able to get some sleep. These D2/D3 partial agonists cause movement disorders more often than even older antipsychs, be careful people, as leokitten pointed out they occupy the D2 receptor with high occupancy% even at 2mg. I think with the partial agonists you really have no way to predict, unless you have schizophrenia, what the drug is going to do at the receptor. There’s no definitive evidence that the D2/D3 receptors are under active in ME.

 

[Dude]

Apologies for the off-topic question.
I've always wondered why Abilify works for some people with ME/CFS and whether it's actually related to dopamine. My doctor suspected that since Abilify worked well, Wellbutrin should also be effective for me, which it wasn't. Lately, there have been increasing reports and medication studies focusing on acetylcholine receptors.

For instance, the nicotine patch trial, the muscarinic acetylcholine group of G receptors , the amifampridine medication trial where 5 people were almost in remission, etc.

I looked into the potential effects of low acetylcholine levels, and surprisingly, it reads almost like ME/CFS symptoms. I wondered if dopamine also affects acetylcholine, and yes, dopamine D2 receptors can influence the release of acetylcholine in certain brain regions. What if this is a receptor issue? It's speculative, of course, just a hypothesis.

 

[hapl808]

Apologies for the off-topic question.
I've always wondered why Abilify works for some people with ME/CFS and whether it's actually related to dopamine. My doctor suspected that since Abilify worked well, Wellbutrin should also be effective for me, which it wasn't. Lately, there have been increasing reports and medication studies focusing on acetylcholine receptors.

For instance, the nicotine patch trial, the muscarinic acetylcholine group of G receptors , the amifampridine medication trial where 5 people were almost in remission, etc.

This all interests me. I have huge crashes from any cognitive stimulation or enjoyment, so dopamine (or norepinephrine) seems likely to be involved. I also have muscular issues.

I'm interested in trying LDA, and even Wellbutrin sounds like it works on all the right receptors. However, I'm also very concerned about trying things that might alter my cognitive abilities. Right now my cognitive function is 'reduced' greatly, but I still feel like me (I think). When I've had really bad crashes (after injuries, allergic reaction, etc), the cognitive symptoms were pretty horrific, but luckily mostly temporary.

I'd love to experiment, but wish we had an UNDO button if things go awry.

 

[SlamDancin]

@Dude I’m also confused because my understanding of the D2 autoreceptor was that activation would result in lower dopamine release. I could be wrong but all these things need to be studied so that we know what is happening in patients that improve from Abilify.

 

[leokitten]

Well I had to stop Cariprazine after just five doses as I was getting the same sleep myoclonus that Abilify was giving me. It prevents me from being able to sleep and it’s hellish, having tremors right as I am falling asleep over and over all night. After around 36 hours post last dose I was able to get some sleep. These D2/D3 partial agonists cause movement disorders more often than even older antipsychs, be careful people, as leokitten pointed out they occupy the D2 receptor with high occupancy% even at 2mg. I think with the partial agonists you really have no way to predict, unless you have schizophrenia, what the drug is going to do at the receptor. There’s no definitive evidence that the D2/D3 receptors are under active in ME.

Have you tried Rexulti? It’s supposed to be less activating the Abilify and has a lower IA at dopamine receptors.

 

[leokitten]

Apologies for the off-topic question.
I've always wondered why Abilify works for some people with ME/CFS and whether it's actually related to dopamine. My doctor suspected that since Abilify worked well, Wellbutrin should also be effective for me, which it wasn't. Lately, there have been increasing reports and medication studies focusing on acetylcholine receptors.

Bupropion doesn’t work because it inhibits reuptake of your own dopamine and norepinephrine, so if we aren’t making enough of these neurotransmitters or something else is dysfunctional with dopamine signaling then bupropion won’t be that effective. Abilify on the other hand functions as a partial agonist with ~60% intrinsic activity (IA) of dopamine and will effectively replace dopamine we aren’t able to make, plus because since it’s a partial agonist then it will stabilize dopamine signaling across the CNS.

 

[SlamDancin]

Apparently Bupropion doesn’t even inhibit DAT at all in people. If it raises dopamine at all it would be through NRI or other mechanisms.

@leokitten i would be afraid to try rexulti at this point. A study I read showed that abilify, rexulti and Cariprazine all inhibited Complex 1 of the ETC and inhibited mitochondrial respiration, causing necrosis of neurons, especially in the motor control area of the brain, explaining their apparent highly prevalence of causing movement disorders. They didn’t test whether a D2/D3 antagonist reversed the damage so not sure if it’s dopamine receptor dependent but yeah, those drugs are all apparently just straight up toxic

 

[leokitten]

Apparently Bupropion doesn’t even inhibit DAT at all in people. If it raises dopamine at all it would be through NRI or other mechanisms.

@leokitten i would be afraid to try rexulti at this point. A study I read showed that abilify, rexulti and Cariprazine all inhibited Complex 1 of the ETC and inhibited mitochondrial respiration, causing necrosis of neurons, especially in the motor control area of the brain, explaining their apparent highly prevalence of causing movement disorders. They didn’t test whether a D2/D3 antagonist reversed the damage so not sure if it’s dopamine receptor dependent but yeah, those drugs are all apparently just straight up toxic

See two review papers about how many antidepressants also inhibit various aspects of mitochondrial respiration. Evidence on damage is really still unfounded and not considered established science especially given how many millions of people have taken antidepressants with no long term issues. The same is true for antipsychotics.

Look at the main figures in these papers you will see a number of widely used drugs inhibit mitochondrial function.

Emmerzaal TL et al. Effect of neuropsychiatric medications on mitochondrial function: For better or for worse. Neurosci Biobehav Rev. 2021

Nuñez NA et al. Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value. J Clin Psychopharmacol. 2023

 

[hmnr asg]

How was your experience with Rexulti? Based on hundreds of anecdotal reviews on drugs.com Rexulti seems to get the best overall users reviews compared to Abilify and Vraylar. Did you find Rexulti less activating than Abilify?

I had no gains from rexulti, and i gave it a few months. Perhaps the dose wasnt correct. I just cut the smallest pill that I could get and cut it in half and did that for about two months. No benefits as far as i remember.

Currently on vraylar and as i mentioned maybe small gains, but everything you said im going to take it every other day since it is actually interfering with my sleep (and has increased my libido, which is not something that is welcomed with cfs).

 

[leokitten]

@hmnr asg thx. Yeah like all of us I’m wondering if tinkering with Abilify succesors will produce a better result. I’m getting the new bottle of Abilify oral solution today and will purposely go back down to 0.5 mg and see what happens. I am hoping having to take 2-3 mg per day and the more slow-building response this third time compared to before was due to the bottle that is expired and has been opened for 2 years

 

[hmnr asg]

@hmnr asg thx. Yeah like all of us I’m wondering if tinkering with Abilify succesors will produce a better result. I’m getting the new bottle of Abilify solution today and will purposely go back down to 0.5 mg and see what happens. I am hoping having to take 2-3 mg per day and the more slow building response this third time compared to before was do to the bottle that is expired and opened for 2 years

I just skipped a dose of my 1.5 vraylar today to see if lower doses would help, but i feel like death today. not sure if its even worth trying to experiment with the dose because i was fairly stable on the 1.5 dose. I will give it another week and then go back (or hek, increase the dose).
ps good luck with the new bottle!