Abilify- Stanford Clinic Patients

[YippeeKi YOW !!]

But for me personally sharing what helps feels a bit like being in a defensive situation.

I agree that it seems that way, but it may just be the way some people process unconventional information: by first questioning it aggressively, then seeming to attack it, then eventually absorbing it.

Please don;t feel personally attacked. Your input has been critical to a lot of people, not all of whom are posting here. This is a controversial treatment protocol, and every bit of first hand, experiential information about it is invaluable, and thank you for your courage in posting here.

what you do with these information is completely up to you.

Totally agree. No one is holding a gun to anyone's head here and demanding that they accept the same treatments or medications that have helped them, especially since we've all pretty much learned that this is NOT a one size fits all illness, and that what helps one of us may not help another, and may actually set yet another one back.

Caveat emptor. Use common sense. Proceed with caution.

And you ggggooo, @Martin aka paused||M.E. .... I applaud your courage, both in trying the Abilify protocol, and in posting about it here for the benefit of others .....

Onward and upward !!!

 

[YippeeKi YOW !!]

It's my speculation that these drugs may stop working the same way as benzos, SSRIs and other antidepressants tend to do over time,

I'm not sure about that.

Benzos work by overstimulating GABAa receptors, flooding them with chemical GABA, causing them to down regulate, since they're no longer necessary to maintain a steady flow of GABA, which leads to complete dependence on the benzo for any GABA response at all, and that leads to unbelievable hellfire and damnation for a large percentage of the population.

Abilfy works as a sort of chemical adaptogen, increasing dopamine where it's too low, decreasing it where it's too high, creating a sort of 'healthy' homeostasis ...

Not saying that some sort of tolerance might not eventually express, but I'm not putting any big bets on 'when' or 'if' either ....

 

[YippeeKi YOW !!]

The half-life for aripiprazole is a lengthy 94 hours. Nearly double that of Diazepam.

Diazepam's half-life ranges as high as 74-78 hours, so not exactly double. Comparably higher in terms of longevity in the brain, but not double ...

B) The half-life is relatively long, so would 2mg every other day will be effective?

Since Abilify is prescribed for ME in a very, very small dose, once it starts decaying towards it's first half life, there might not be enough in the system to make a sufficient difference ...

Abilify is extensively metabolized in the liver mainly by the CYP2D6 and CYP3A4 enzymes whereas diazepam, while also demethylized by the CYP3A4, is also primarily metabolized by the CYP2C19 enzyme system .... so slightly different mechanisms in play which could make a big difference ....

 

[choochoo]

Diazepam's half-life ranges as high as 74-78 hours, so not exactly double. Comparably higher in terms of longevity in the brain, but not double ...

Since Abilify is prescribed for ME in a very, very small dose, once it starts decaying towards it's first half life, there might not be enough in the system to make a sufficient difference ...

Abilify is extensively metabolized in the liver mainly by the CYP2D6 and CYP3A4 enzymes whereas diazepam, while also demethylized by the CYP3A4, is also primarily metabolized by the CYP2C19 enzyme system .... so slightly different mechanisms in play which could make a big difference ....

When I start my Abilify trial, I will be starting on 1mg ( or less ) every other day for the first month. If there is a marked beneficial response I will remain at that. If not, I will move to 2mg every other day for another month and then go from there. I will report back with my findings in due course.

 

[YippeeKi YOW !!]

When I start my Abilify trial, I will be starting on 1mg ( or less ) every other day for the first month. If there is a marked beneficial response I will remain at that. If not, I will move to 2mg every other day for another month and then go from there. I will report back with my findings in due course.

A very sensible approach, allowing your body and brain to kinda let you know what they think about all this .... and if 1 mg (or even less) every other day does the job, why take more? Abilify isn't without potential backlash, and I've always believed that the less of anything you can take to get good results, the better ....

Please do report back .... we'll be anxious to know how you'e doing, and how your well-thought-out Abilify regimen is working for you.

Onward and upward !!!

 

[YippeeKi YOW !!]

Any drug that causes tolerance over time should be very concerning, and one should think very hard about the consequences before taking one. There are many other drugs and supplements that are far safer and do not induce tolerance.

While I totally agree with you, and am appalled at the way so many Drs, from dentists to dermatologists and gynecologists to gastroenterologists hand out mind and spirit bending psycho-actives like anti-d's, anti-convulsants (touted by their manufacturers as being effective against anxiety, depression, you name it, altho they were developed for epileptic seizures which sadly, didnt produce the expected revenue streams), anti-psychotics, anti-anxiety drugs, benzodiazepnes, and the coyly named Z-Drugs, (which are benzos in a hipper suit) like they were party favors at very large wedding.

The truth is that used judiciously and with thoughtful and informed oversight, they can be a life saver, short term, for a lot of people.

But they never seem to be prescribed short-term, and Drs rarely, if ever, warn their patients about the fire-breathing dragons waiting at the end of that tunnel when the Dr, for whatever reason, decides to take their patients off them, usually waaaaaay too fast, causing indelible, long term, sometimes life-time damage to a structure that the more honest among them will admit that none of them really understands fully, or often at all: the brain and the CNS.

And another aggravating truth is that our bodies will become acclimated to everything from vitamin supps to herbs to facial moisturizers and shampoos, inhibiting their initial good effects, which is why it's so often suggested to 'pulse' them, especially herbs, so your body doesn't have a chance to decide, "Well, enough of that .... next please ..... ", and launch us into the constant, endless search for something similar that will work as well as the original did, before it stopped working at all.

But pulsing isnt really always possible with psycho-actives, especially after your brain/body/CNS have become dependent on them to perform the tasks your brain etc used to do effortlessly, but now no longer can, which can happen pretty quickly if you're genetically unlucky.

You can, however, start as low as possible, establish the smallest dose that produces the desired effect, then experiment carefully with that using a variation of one-day-on-two-days-off, or one on, one off, or whatever works for your body and circumstances, extending, sometimes dramatically, the period of time that the substance you're taking will remain fully effective.

Wow !!! A LOT of very long sentences here .... I apologize. I'm tired and a little brain dead, but I hope this proves helpful to someone, at some point, somewhere here in the PR Universe ....

As ever, onward and upward !!!

UPDATE FOR THIS ARTICLE I CAME ACROSS THIS MORNING:

Popular anti-anxiety medications may be highly addictive, FDA says. But is the warning too late
https://www.yahoo.com/gma/popular-anti-anxiety-medications-may-100600932.html

My guess? Nothing will change. But the warning's out there now, so caveat emptor .... not you, @Martin aka paused||M.E. , cause what you're doing is well-considered, researched, and under careful supervision for a devastatingly debilitating and currently incurable condition. Better yet, it's working for you !!!!

 

[Alesh]

Amisulpride, aripiprazole (Abilify) and lurasidon--These three antipsychotics help me but I have hypoglycemia/hyperphagia after them so I don't take them every day. Their effect and what unique these three antipsychotics have is 5-HT7 antagonism.

 

[choochoo]

Amisulpride, aripiprazole (Abilify) and lurasidon--These three antipsychotics help me but I have hypoglycemia/hyperphagia after them so I don't take them every day. Their effect and what unique these three antipsychotics have is 5-HT7 antagonism.

Hi

This is very interesting. Have how long have you been taking Amisulpride and have you any 'permanent' side effects?

Also, are you a diagnosed diabetic?

 

[andyguitar]

Their effect and what unique these three antipsychotics have is 5-HT7 antagonism.

That's an interesting observation @Alesh as abnormalities of 5-HT7 could be a factor in me/cfs.

 

[Alesh]

Hi

This is very interesting. Have how long have you been taking Amisulpride and have you any 'permanent' side effects?

Also, are you a diagnosed diabetic?

I have been taking amisulpride since 2004. Then in 2011 I started suddenly to gain weight and also my breasts swelled because of this so I reduced the dose to 50mg every other day. I am not diagnosed diabetic but who knows if I have diabetes I am totally bedbound. I have no permanent side effect like tardive dyskinesia.

 

[leokitten]

It’s clear to all of us suffering with ME that the underlying disease pathology has very significant neurological effects. One effect could be significant dysregulation of various neurotransmitters or dysregulation of neuronal firing and this might contribute to some symptoms and Abilify might help with this dysregulation in some people.

But as someone pointed out Naviaux saying, this is symptomatic treatment and likely isn’t disease modifying or giving us any insight towards the core pathology of ME. I do hope though it continues to work in those people who are taking it and have seen a benefit.

What I would like to see is in those who are taking Abilify is if it consistently helps with PEM or other important symptoms after you increased exertion and that these effects continue over time. The problem with ME is empirical treatments available so far show no symptom improvement at all or they only seem to improve some symptoms for a short time before becoming useless.

 

[hmnr asg]

I suggest reading this thread about amisulpride by @Hip :
https://forums.phoenixrising.me/threads/amisulpride-a-multipurpose-drug-for-me-cfs.20964/

And this thread talking about the combination of antidepressants with third gen antipsychotics:
https://forums.phoenixrising.me/thr...-used-to-treat-me-debilitating-fatigue.50775/

I think as @Hip emphasizes we need to be on *low* dose of abilify or amisulpride since the mechanism of the drug is completely different on lose dose and high dose. He takes very small doses.

@leokitten I agree with you 100% that this isnt any kind of real cure. I personally just want to be able to shower once in a while and be able to play with my cat once in a while. I frankly dont think I will see a real cure in my lifetime

 

[leokitten]

@leokitten I agree with you 100% that this isnt any kind of real cure. I personally just want to be able to shower once in a while and be able to play with my cat once in a while. I frankly dont think I will see a real cure in my lifetime

Sorry @hmnr asg I was updating my post with more commentary in middle of your reply my typing is really shitty today. Maybe what I added shows what I mean more clearly. I do hope Abilify can work for people who try it and help people have enough symptom improvement that they can do more self care.

 

[leokitten]

This thread discussing some preliminary research work from the James Neuroimaging Lab at Stanford where they used their TSPO-PET/MRI technique and found increased neuroinflammation in the basal ganglia of ME/CFS patients compared to matched healthy controls.

Maybe Abilify helps here and not necessarily by decreasing neuroinflammation as there is no real evidence that it does, it could be that neuroinflammation here causes dysregulation of neuronal firing or neurotransmitters in the basal ganglia and Abilify might help counteract some of the downstream effects.

 

[hmnr asg]

The problem is that its hard to disentangle correlation and causation. There have been many studies that have shown difference between some measured quantity between CFS patients and healthy people. But is that particular biomarker indicative of the cause of the disease? or just the result of CFS messing with another system in the human body.

 

[leokitten]

This thread discussing some preliminary research work from the James Neuroimaging Lab at Stanford where they used their TSPO-PET/MRI technique and found increased neuroinflammation in the basal ganglia of ME/CFS patients compared to matched healthy controls.

Maybe Abilify helps here and not necessarily by decreasing neuroinflammation as there is no real evidence that it does, it could be that neuroinflammation here causes dysregulation of neuronal firing or neurotransmitters in the basal ganglia and Abilify might help counteract some of the downstream effects.

I also read in research discussing immune dysfunction in schizophrenia, that uncontrolled microglial activation, release of pro-inflammatory cytokines, and resultant neuroinflammation can result in neurotransmitter dysregulation. So this hypothesis about Abilify might make sense, not that it’s doing anything about ME-related neuroinflammation, but that it’s helping in some way with neurotransmitter dysregulation in some patients.

But that being said I want to see if it works for these patients long term and quantitatively by how much, eg steps, increased exertion and reduced PEM, etc.

Neuroinflammation and neuroimmune basis for schizophrenia:

Neuroinflammation and Schizophrenia

Neuroinflammation in Schizophrenia: A Critical Review and The Future

 

[leokitten]

This also made me think that if there is such significant chronic microglial activation, release of proinflammatory cytokines, and neuroinflammation in ME then why aren’t we seeing significant neurodegeneration and brain atrophy in MRIs of pwME?

 

[leokitten]

Very interesting paper on new findings regarding Abilify mechanism of action

Update on the Mechanism of Action of Aripiprazole: Translational Insights into Antipsychotic Strategies Beyond Dopamine Receptor Antagonism

 

[choochoo]

I have been taking amisulpride since 2004. Then in 2011 I started suddenly to gain weight and also my breasts swelled because of this so I reduced the dose to 50mg every other day. I am not diagnosed diabetic but who knows if I have diabetes I am totally bedbound. I have no permanent side effect

Microglia
These, CNS-specific phagocytic mononuclear cells (Wolf et al. 2017), are produced in the yolk sac and migrate during early CNS development, before the blood brain barrier is formed. In adult life, microglia are involved in a number of homeostatic functions, including neurogenesis, synaptogenesis and synapsis remodeling, as well as neuronal apoptosis and removal (Li and Barres 2018). Microglia also actively survey the CNS for preserved molecular patterns suggestive of infection (pathogen-associated molecular patterns [PAMPs]) and tissue injury (damage-associated molecular patterns [DAMPs]) (Sankowski et al. 2015; Salter and Stevens 2017). Adult microglia express several serotonin receptors, including 5-HT2a, 5-HT2b, 5-HT5a, and 5-HT7 receptors (Krabbe et al. 2012). Microglia express at least two splice variants of the 5-HT7 receptor: 5-HT7(a/b). In these cells, the administration of serotonin, as well as 5-carboxamidotryptamine (5-CT) induces an inflammatory priming and IL-6 production, indicating that these receptors may play a role in CNS inflammation and repair (Mahé et al. 2005).

 

[choochoo]

The above is a theory involving the 5HT-7 receptor and CFS. In theory this receptor actively seeks out and monitors inflammation and infection. If found, the receptor then 'assists' in the body's immune reaction. Its a simple but possible theory for everything we all have to put up with. If the theory is correct it takes us a long way by explaining why Aripiprazole may move the needle in the very severe. It's a similar explanation to the " cell danger response " theory. It is the last sentence that interests me."In these cells, the administration of serotonin, as well as 5-carboxamidotryptamine (5-CT) induces an inflammatory priming and IL-6 production, indicating that these receptors may play a role in CNS inflammation and repair (Mahé et al. 2005)".