Martin aka paused||M.E.
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Abilify- Stanford Clinic Patients
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@Martin aka paused||M.E. I’m not entirely sure that there’s any consensus that low dose Abilify helps many ME symptoms because we just have dopaminergic hypofunction and that Abilify corrects for this. Your theory on tolerance seemed to be based on this pathology? Because then why wouldn’t stimulants, bupropion, other ADHD meds, or dopamine agonists etc help us? They really don’t work at all. I think what Abilify is doing to help might be more complex than that, and since it is multimodal (dopamine and serotonin stabilizer, anti-inflammatory, immunomodulating and cellular metabolic effects, etc) it’s hard to know how it’s helping and what then causes tolerance to develop after weeks or months.
I’m not saying that your theory isn’t worth trying on yourself, go for if you want. But from one person with ME for whom Abilify worked twice to another, I never personality felt like it was just increasing my dopamine function, and stimulants, bupropion, dopamine agonists never worked for me. Many of the symptoms of this illness don’t feel like they come from dopamine hypofunction, yet Abilify made these symptoms temporarily improve dramatically or go away as well.
If I were to give a subjective explanation of how it feels, it’s like all the inflammation in my CNS and feeling of chronic low grade peripheral immune activation and body pain simply melt away and I become myself again, for a while until it starts creeping back in.
I’m not saying that your theory isn’t worth trying on yourself, go for if you want. But from one person with ME for whom Abilify worked twice to another, I never personality felt like it was just increasing my dopamine function, and stimulants, bupropion, dopamine agonists never worked for me. Many of the symptoms of this illness don’t feel like they come from dopamine hypofunction, yet Abilify made these symptoms temporarily improve dramatically or go away as well.
If I were to give a subjective explanation of how it feels, it’s like all the inflammation in my CNS and feeling of chronic low grade peripheral immune activation and body pain simply melt away and I become myself again, for a while until it starts creeping back in.
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YippeeKi YOW !!
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Hi @Martin aka paused||M.E. .... you've been flitting through my mind, which is saying a lot right now. because I;m dealing with a world of difficulties, drama, and symptomatic reactions to same .... It's good to know that you're still working on your plan, and to see you pop in from time to time, tho I wish it were for a happier reason ... sending a large hug to you and your g'friend ..... Your Forever Fan ....
On a related note, Martin’s posts made me think, has anyone tried low dose Abilify with an antidepressant, like low dose Abilify with bupropion or SSRI or latest gen atypical antidepressant (vilazodone, vortioxetine)? The latest gen antidepressants supposedly not only have fewer side effects than SSRIs/SNRIs, but they also have multimodal mechanism of action on different serotonin receptors not just SERT reuptake inhibition. Or even low dose Abilify combined with anything else that looks like it would work synergistically? Like for example an idea: combining Abilify with guanfacine or atomoxetine. If the dopamine hypofunction hypothesis is at least partially real, then maybe these non-stimulant ADHD meds could combo with Abilify. Or if they just promote overstimulation and then PEM it would mean like stimulants it’s not just about increasing dopamine function.
Has any of this helped with ME symptoms? I know many of us have reactive depression after years of having ME with no hope, but if you’ve tried any of these combos and could delineate between depression symptoms and ME symptoms and whether it helped with the latter?
Has any of this helped with ME symptoms? I know many of us have reactive depression after years of having ME with no hope, but if you’ve tried any of these combos and could delineate between depression symptoms and ME symptoms and whether it helped with the latter?
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The Stanford study found no statistically significant effect of concurrent antidepressant use on Abilify's effectiveness in ME/CFS:
"The difference in antidepressant use between responders vs. non-responders was not statistically significant (p = 0.145) using the test for proportions, suggesting that antidepressant use does not predict or preclude a clinical response to aripiprazole."
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02721-9
Right, but this study didn’t tell us which classes of antidepressants patients were using and didn’t do any analysis wrt this, so as a big single group of concurrent antidepressant use of multiple types it would squash any possible signal coming from specific types of antidepressants or other drugs. Maybe SSRIs/SNRIs have no synergistic effect (the most common antidepressant classes) but atypical ones like bupropion, vilazodone, vortioxetine, or non-stim ADHD meds etc might show some synergistic signal. We’ll never know from this non-conclusive study.
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That's true. But there are so many possibilities for how Abilify might work in ME/CFS. Other pathways might have stronger evidence.
Some examples:
https://pubmed.ncbi.nlm.nih.gov/35044019/
Some examples:
The antipsychotic aripiprazole induces peripheral antinociceptive effects through PI3Kγ/NO/cGMP/KATP pathway activation
Interesting snippet:(note: antinociceptive = decreasing sensory/pain sensitivity)
https://pubmed.ncbi.nlm.nih.gov/35044019/
The effect of acute aripiprazole treatment on chemically and electrically induced seizures in mice: The role of nitric oxide
https://pubmed.ncbi.nlm.nih.gov/26037847/Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro
https://pubmed.ncbi.nlm.nih.gov/18429930/@bob800 totally agree, see my posts above to @Martin aka paused||M.E. just made me wonder if people had tried these various other combos to give us more data on whether an ME dopamine hypofunction partial hypothesis for Abilify is possible
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@hmnr asg did you ever trial low dose brexpiprazole (Rexulti)? Another way we could understand better what mechanism Abilify might have in ME is if people who tried other drugs of this class at low dose and we see similar effects.
@jaybee00 how are you? On the FBK, Reddit, and Discord ME Abilify groups did people report similar effects from other low dose antipsychotics?
@jaybee00 how are you? On the FBK, Reddit, and Discord ME Abilify groups did people report similar effects from other low dose antipsychotics?
Don't have a ton to add as someone who hasn't trialed LDA quite yet.
I wish someone had continued Goldstein's research, as he seems to have looked at a lot of this stuff. From Tuning the Brain (I just OCR'ed a small section and tried to correct some subscripts, so don't take this as the gospel).
I think Abilify had just been released when Tuning the Brain came out so it's only mentioned once in his discussion of dopaminergic autoreceptors. He also mentions DS121 and OSU6162, which AFAICT are still in trials.
He has various discussions of tolerance, sensitization, etc. Might be worth looking at with the benefit of your research which wouldn't have been available to Goldstein in 2004.
I really don't know enough to say if any of this is related, and I don't think we really know what LDA is doing when it does (or doesn't) work, but Goldstein's stuff at least sounds like it's in vaguely the same ballpark, even more remarkable that it's 20 years old. I just wish someone like him had continued down this path for both research and treatment.
The only thing I can think to add to what @hapl808 said is with olanzapine or some similar earlier generation atypical antipsychotics compared to later generation atypicals is that the earlier generation definitely have more side effects and long-term effects. Olanzapine can make you binge eat and I believe it has one of the highest weight gain issues of all antipsychotics.
It totally messes with the body’s metabolic and endocrine state and therefore increases fasting blood glucose, cholesterol, triglycerides, prolactin, risk of type 2 diabetes etc. Not to mention also higher risk of CNS issues EPS, akathisia, etc.
It has a much higher risk of all these typical antipsychotic side effects compared to Abilify were these risks are lower especially at low dose. I think some doctors prescribe metformin with olanzapine to reduce some of the bad metabolic effects.
It totally messes with the body’s metabolic and endocrine state and therefore increases fasting blood glucose, cholesterol, triglycerides, prolactin, risk of type 2 diabetes etc. Not to mention also higher risk of CNS issues EPS, akathisia, etc.
It has a much higher risk of all these typical antipsychotic side effects compared to Abilify were these risks are lower especially at low dose. I think some doctors prescribe metformin with olanzapine to reduce some of the bad metabolic effects.
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Thanks @jaybee00 for some of this anecdotal info, which I know isn’t super reliable we don’t know for sure if those people actually have same ME as others who responded to low dose Abilify, but we can start looking at the shared known mechanisms of action between these drugs and Abilify. I will look at it tomorrow.
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Martin aka paused||M.E.
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do you know what dose of cariprazine they take? thank you
hmnr asg
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I tried rexulti (it wasn't cheap since there is no generic). What happened was maybe 2 days of improvements and then reverted back to baseline. It was almost the same response as I would have expected from abilify after the long break, which makes sense since they are so similar.
I also tried amisulpride (@Hip has a very nice and detailed post about it) at the dose that he recommended. Its also an atypical antipsychotic but its not approved in the US so i had to buy it from an online pharmacy. I think @Hip said that he got calming effects from it, but for me the effects were the opposite. It felt like I was experiencing serotonin syndrome: agitation, restlessness, fast heart rate... I was really freaked out and never tried it again.
ps as always when sharing my experience I like to mention the other related meds im currently on: duloxetine 30mg/day, pregabalin 150mg/day, occasional benzos and melatonin. (Not sure what interactions it might have had with antipsychotics have but I had to mention in case someone finds it relevant).
ps @Martin aka paused||M.E. we interacted on the facebook group for LDA and I mentioned that I will try rexulti and amisulpride and report back. Sorry I never got to do it, but here it is.
Thanks for the details @hmnr asg. I can say from my experience I was taking moclobemide every day (MAO-A inhibitor antidepressant), and once or twice a week gabapentin, eszopiclone (sort of benzo), and melatonin during both my LDA trials where each time it improved ME symptoms tremendously for me for months and these other drugs didn’t seem to have a negative effect. Though I can’t tell you if without some or all of these other drugs if LDA would’ve worked longer.
Since these other meds I took during LDA were similar to yours I’m guessing yours didn’t contribute much to LDA not working for you again. Though of course only two anecdotal comparisons. But like mentioned above antidepressant use seemed to have no synergetic or negative effect on LDA supposed efficacy in the Stanford retro study.
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Btw brexpiprazole became generic in the US last year after court battles against Ostuka and Lundbeck, but funny even today when you look it up on GoodRx you can find it and the dosages but seems like no pharmacy carries it yet and no prices? Weird
hmnr asg
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I just checked my online pharmacy and they dont have the generic listed either.
What i did is to use the coupons on the manufacturer website to get a steep discount (I paid almost nothing). I think you can get 3 months worth of it for very little if you use the coupon, and since we are doing low dose and not the whole pill this will go a long way (if it works hopefully, which I doubt if abilify is not working).
Here is the link: https://www.rexulti.com/savings
Supposedly brexpiprazole and cariprazine, because they have a lower intrinsic affinity at dopamine receptors than aripiprazole, function differently than aripiprazole at low and high doses, they actually function in the opposite manner. See the Wikipedia page on brexpiprazole for the explanation. This info could be wrong honestly, because these three drugs with similar molecular structures already have quite high dopamine receptor occupancy at low doses, and since they are partial agonists you would think no matter what at higher doses they will block more since IA much less than dopamine.
Supposedly from that Wikipedia page aripirpazole has an intrinsic affinity of 60%+ depending on dopamine receptor subtype and therefore increases dopaminergic neurotransmission while balancing at lower doses and it’s more blocking at higher. Whereas brexpiprazole is about 45% and cariprazine 40% so it’s said there they actually increase dopamine neurotransmission at higher doses and blocking at lower.
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.
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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.