Abilify- Stanford Clinic Patients

[hmnr asg]

Maybe dopamine actions are only part of the mechanisms that help ME, just throwing this out there wondering if dosing would work differently for brexpiprazole and cariprazine than aripiprazole.

I'm still skeptical about this theory that the LDA effects on dopamine are causing the improvements in CFS. If that was the case why not use strictly dopaminergic meds like Mirapex (https://en.wikipedia.org/wiki/Pramipexole) ?
shouldn't they have an even stronger effect on dopamine receptor? I haven't heard of anyone getting benefits from them (or have they or I just didn't come across it?)
I think we have been over this question but I'm still confused.

 

[leokitten]

I'm still skeptical about this theory that the LDA effects on dopamine are causing the improvements in CFS. If that was the case why not use strictly dopaminergic meds like Mirapex (https://en.wikipedia.org/wiki/Pramipexole) ?
shouldn't they have an even stronger effect on dopamine receptor? I haven't heard of anyone getting benefits from them (or have they or I just didn't come across it?)
I think we have been over this question but I'm still confused.

Totally agree (see my above posts to Martin). This recent discussion made me ask myself, if since we think it’s probably not all about dopamine, and that makes sense, why do very low doses of Abilify help a lot but somewhat higher doses don’t? If it’s due to anti-inflammatory or immunomodulating effects for example why would somewhat somewhat higher doses not help more?

 

[leokitten]

One person on the FB group takes .75 mg vraylar (cariprazine) and says it’s a bit better than Abilify, but generally pretty similar.

Also if you pm/dm me your email I can forward you an email related to dosing frequency.

Unfortunately here in the US Vraylar is still not generic, but hopefully in Germany

 

[bob800]

If that was the case why not use strictly dopaminergic meds like Mirapex (https://en.wikipedia.org/wiki/Pramipexole) ?
shouldn't they have an even stronger effect on dopamine receptor?

Actually there are anecdotes on this forum of dopamine agonists substantially helping ME/CFS symptoms.

Pramipexole + LDN: https://forums.phoenixrising.me/threads/how-i-solved-my-neuroinflammation.81625/

Cabergoline + ITPP:
https://forums.phoenixrising.me/thr...eatment-can-anyone-please-explain-this.80654/

I would be very interested to know if these members continue to get benefit over the long-term from these drugs. It's also interesting that both posters only derived significant benefit when the dopamine agonist was combined with another drug (LDN or ITPP).

 

[nolongerdiseased]

I also think that when you contract this illness at a younger age, you have more of an opportunity to basically stop you life to do what is needed to recover. If I had gotten sick in my 20s or earlier I could’ve basically closed up shop on my life, moved in with my parents, and focused 100% on recovery. You simply can’t do that when you are older, you have a ton more responsibilities and you can’t just quit everything for however long it takes, which is what is needed for ME recovery, society for adults just isn’t built to support this.

So it’s all too common that we spend the first crucial years pushing and crashing and doing everything wrong we had no choice. I got sick at 37 I don’t know for sure but if I could’ve just quit life and focus on recovery the first 2-3 years it might’ve made a difference.

I've considered what it would be like if I were to relapse again later in life, and I do think this is one of the major positives of getting the disease so young. I didn't have to worry about rent, about how I was getting the money to feed myself or how I was going to do general life duties like cooking and cleaning.

As for the Abilify, it definitely was vital in my remission but I can't speak to its longevity as I was only on it for 2-3 months. I assume the dopamine upregulation and whatever other mechanisms further regulated my already improving immune state. At the point I started taking it I was very mild, improved from my baseline of mild/50% function, which is just a completely different beast than improvements in disease when you are moderate or severe.

 

[hmnr asg]

Actually there are anecdotes on this forum of dopamine agonists substantially helping ME/CFS symptoms.

Pramipexole + LDN: https://forums.phoenixrising.me/threads/how-i-solved-my-neuroinflammation.81625/

Cabergoline + ITPP:
https://forums.phoenixrising.me/thr...eatment-can-anyone-please-explain-this.80654/

I would be very interested to know if these members continue to get benefit over the long-term from these drugs. It's also interesting that both posters only derived significant benefit when the dopamine agonist was combined with another drug (LDN or ITPP).

Then how come none of us are trying Pramipexole? If dopamine is the key that should be the drug of choice I would think.
@leokitten @Martin aka paused||M.E. what do you think? maybe we ought to give it a try!
I am surprised how come nobody seems to have tried it on the LDA facebook group. So many of us have had LDA stop working on us, it seems to be the next logical step?

@leokitten
If dopamine is not the key, I don't think immunomodulation or anti-inflammatory properties would be the explanation for why LDA works. There are many more potent drugs in those classes that don't have any positive impact on CFS.
I think it's either dopamine (in which case lets try pramipexole) or its something entirely different if not that.
I am going to make an appointment with my psychiatrist right now to ask for Pramipexole.

 

[leokitten]

I’ve tried dopamine agonists actually all the way back in 2014, long before I knew of Abilify. They didn’t work for me. I tried both pramiprexiole and ropinirole or cabergoline (can’t remember which). I also tried MAO-B inhibitors selegiline and rasagiline. None of these worked.

Also, only a couple or handful of anecdotal reports on dopamine agonists is nothing, on PR we could find a couple anecdotal reports of chakra crystals helping ME patients. It’s no where near the likely thousands of anecdotal reports all saying the same positive effects of LDA.

 

[leokitten]

I’ve tried dopamine agonists actually all the way back in 2014, long before I knew of Abilify. They didn’t work for me. I tried both pramipexole and ropinirole or cabergoline (can’t remember which). I also tried MAO-B inhibitors selegiline and rasagiline. Nothing worked.

A couple anecdotal reports on dopamine agonists is not much to go on, on PR we could find a couple anecdotal reports of chakra crystals helping ME patients. It’s no where near to the likely thousands of anecdotal reports all saying the same positive effects of LDA.

Actually there are anecdotes on this forum of dopamine agonists substantially helping ME/CFS symptoms.

Pramipexole + LDN: https://forums.phoenixrising.me/threads/how-i-solved-my-neuroinflammation.81625/

Cabergoline + ITPP:
https://forums.phoenixrising.me/thr...eatment-can-anyone-please-explain-this.80654/

I would be very interested to know if these members continue to get benefit over the long-term from these drugs. It's also interesting that both posters only derived significant benefit when the dopamine agonist was combined with another drug (LDN or ITPP).

I think for both those people @Swim15 and @stefanosstef likely both those combos stopped working or working as well. The problem with people on PR is they aren’t generally good at following up long term and say it failed in the end or I’m in remission.

 

[hmnr asg]

Also, only a couple or handful of anecdotal reports on dopamine agonists is nothing, on PR we could find a couple anecdotal reports of chakra crystals helping ME patients. It’s no where near the likely thousands of anecdotal reports all saying the same positive effects of LDA.

I looked in the facebook group (LDA for CFS) and I couldnt even find anecdotal stories. In fact I saw a few comments that seem to indicate it did nothing for them.
Dang, got excited for nothing. Sorry.
but I will add it to the list of things to try, but at the bottom.

 

[Viala]

It is interesting that Abilify works for a while, then it stops working and after a couple of months it starts to work again. What if the dose was too high in the first place and the solution here is to lower the dose and wait longer for a remission to kick in?

 

[Andryr]

after a couple of months it starts to work again

Are there many for whom it works like this? I've only seen a couple of posts in the Abilify group in Facebook.

 

[hmnr asg]

Are there many for whom it works like this? I've only seen a couple of posts in the Abilify group in Facebook.

You are correct, no idea what op is talking about

 

[Viala]

Are there many for whom it works like this? I've only seen a couple of posts in the Abilify group in Facebook.

I've seen only a couple of posts as well.

 

[gm286]

I posted about some “vague” thoughts I had regarding why I think Abilify works. I am not on it any longer (once more) due to the unmanageable side effects (weight gain at even 0.25mg/ml). Not just weight gain — bloat, practically inflating around the midsection.

It working / ceasing to work obviously has something to do with its metabolic effects, not sure why this has not been pondered more.

Not a scientist so excuse the phrasing — it is “doing something” to the sugar pathways. It could be exerting some stimulatory effect upon the pancreas. I definitely did not metabolize sugar, while on the drug, the same way. It just made the side-effects worse (more bloat), as if the sugar was not absorbed or properly used (who knows).

Abilify is to the body what Adderall or another is to the brain — it stimulates, in this case, the whole body instead of just the brain.

While on the Abilify, my A1c marker (diabetes) had been rising steadily. It no longer has. That marker apparently describes how well / poorly glycolysis is taking place upon red blood cells.

All these parameters make me think it works because of its metabolic effects. It stimulates / promotes more sugar uptake (for energy, of course). It stops working when our other pathways can no longer burn / uptake the sugar.

 

[leokitten]

Are there many for whom it works like this? I've only seen a couple of posts in the Abilify group in Facebook.

I’ve done two trials of LDA that worked well and pretty much the same with each lasting a few months before having to stop. I took a pause of 6 months in between. I will do a third trial this year.

 

[hmnr asg]

@leokitten I think (pure broscience speculation) the effects of LDA are due to dopamine. I think that because when I was in a partial remission after starting LDA i felt like my brain's reward circuitry was back online. Also, a very large number of CFS folks seem to have ADHD-like symptoms secondary to CFS which may be caused by a change in dopamine circuitry.

But I dont think its a simple matter of increasing or decreasing dopamine. Since abilify is a partial agonist it may be doing something more complicated than a dopaminergic medication like pramipexole. Also there are five dopamine receptor subtypes and different meds seem to effect each different, could that be a clue? maybe one of those subtypes is the key.

If you check out this table:
https://en.wikipedia.org/wiki/Atypical_antipsychotic#Binding_profile

It seems the only meds that seem to work are the ones that are partial agonists at the dopamine receptors.

Also it seems the only partial agonists at the dopamine receptor are the three meds we have mentioned so far: abilify, rexulti and cariprazine.

So, do we need more dopamine or less? why is a partial agonist any better than a pure agonist? are their effects on each dopamine receptor subtype a clue to why they work? so many questions.

 

[leokitten]

@leokitten I think (pure broscience speculation) the effects of LDA are due to dopamine. I think that because when I was in a partial remission after starting LDA i felt like my brain's reward circuitry was back online. Also, a very large number of CFS folks seem to have ADHD-like symptoms secondary to CFS which may be caused by a change in dopamine circuitry.

I think a lot of pwME might disagree here based on their personal experience. I for one didn’t feel any change to my reward/motivation pathways both times I took LDA and went into temporary partial remission. Hope I can explain it better below. I also haven’t heard that a lot of pwME have ADHD-like symptoms, I certainly don’t and haven’t heard that before?

For me LDA makes the ME debilitating symptoms dramatically improve or disappear, this crushing weight is what is preventing my motivation and reward, not because there’s something broken with the pathway. Then what happens is I just become my old self again, the person I have been all the time but couldn’t get through because I don’t have this huge weight of symptoms punishing me every second of the day.

Normally it feels like my brain is hugely inflamed and feels damaged like I’ve had head trauma, my eyes hurt with light, my ears ringing all the time, my bones and muscles ache very badly all the time, I can’t keep my balance, I have terrible headaches, and much more, but once those are taken away by LDA I can be the person inside I’ve always been and I just jump back to life.

So in my experience I think LDA isn’t activating my reward/motivation pathway more than removing all the debilitating symptoms that get in the way of my motivations and reward that have always been there.

 

[leokitten]

So, do we need more dopamine or less? why is a partial agonist any better than a pure agonist? are their effects on each dopamine receptor subtype a clue to why they work? so many questions.

Partial agonists increase dopamine neurotransmission in brain areas where there’s too little, and decrease dopamine neurotransmission in areas where there’s too much. The intrinsic affinity of the drug at dopamine receptors and the dosage you take is directly tied to how this works

But I think we are missing with all these drugs that they do just as powerful things to the serotonin system, via partial agonism and antagonism at various receptor subtypes and in synergy to the dopamine partial agonism. And as you and others know, antagonism, depending on receptor, isn’t necessarily turning off serotonin, it can be doing the opposite in certain brain areas because the receptor is inhibitory or it’s antagonism could be causing downstream changes in other neurotransmitters.

 

[leokitten]

While on the Abilify, my A1c marker (diabetes) had been rising steadily. It no longer has. That marker apparently describes how well / poorly glycolysis is taking place upon red blood cells.

All these parameters make me think it works because of its metabolic effects. It stimulates / promotes more sugar uptake (for energy, of course). It stops working when our other pathways can no longer burn / uptake the sugar.

This is totally plausible and we’ve discussed this theory before, research has shown that Abilify (and similar Vraylar, Rexulti) have potent cellular metabolic effects that prevent cells from either bringing glucose into the cell or utilizing it as effectively (I forgot), so it could be that in ME this effect somehow pushes our particular cellular metabolism dysfunction back towards normal, at least temporarily.

 

[hmnr asg]

I think a lot of pwME might disagree here based on their personal experience. I for one didn’t feel any change to my reward/motivation pathways both times I took LDA and went into temporary partial remission. Hope I can explain it better below. I also haven’t heard that a lot of pwME have ADHD-like symptoms, I certainly don’t and haven’t heard that before?

In terms of ADHD like symptoms, I think you don't notice it much on the PR forum because we are an older crowd and not trying to study for exams or anything like that.

But i spend a lot of time on the CFS subreddit where the average age is way lower than here and a lot of posts are about how either the person is struggling with ADHD along with CFS or how CFS has destroyed their ability to maintain focus.

You might explain it in terms of fatigue preventing them from paying attention, but the same people are always complaining about too much screen time, so it really does feel like their ability to direct their attention has been compromised as a result of CFS. They either say explicitly that they are suffering from ADHD or they describe ADHD-like behavior.

Whether or not this is connected to dopamine circuitry and whether or not that is the cause of CFS or a symptom of it, i have no idea! But I am sure i have observed a lot of ADHD-like symptoms on the CFS subreddit. In addition, i myself am suffering from ADHD and i am in my 40s and I know for a fact this wasn't the case pre-cfs. I graduated top of my class both in highschool and in university, so i don't have ADHD (otherwise it would have showed up in my younger years). But right now I have the attention span of a jack russel on coke.