Abilify- Stanford Clinic Patients

[Hutan]

The problem is, and I feel ME clinicians know this, is the likelihood of multiple ME subsets, misdiagnosed ME patients, and other unknown confounding factors, that without some knowledge of pathophysiology in at least one subset then drug trials for drugs that really could work for a subset are doomed.

I currently think we need to understand more than near zero about ME and have more accurate diagnostic capabilities before RCTs are really worth spending the resources to do. So in that sense I disagree with many from S4ME and understand much more why patients and doctors experiment with off-label treatments.

But, by using a placebo treatment arm and blinding, even if quite a small percentage of participants have a significant response to the drug, then that will probably show up in the treatment averages. If researchers include a scattergram when reporting on a blinded trial, and relevant outcomes are chosen, then it's likely that good responses in any significant subset will be obvious. And that can lead to a closer look at what it is about those responders that is different to others, and to larger trials by other researchers, to see if there continues to be a subset of responders.

The cost of an RCT is not that much compared to the many costs of not doing RCTs, including
* many patients travelling to try a treatment that doesn't work;
* many patients losing credibility with their doctors and family and friends when they try to try an unproven treatment;
* many patients needlessly suffering side effects;
* clinicians damaging their reputations by promoting unproven treatments;
* the understanding of ME/CFS being delayed, as dead ends aren't quickly discarded and promising leads aren't followed up by a range of researchers;
* successful treatments not being accorded the credibility that they should have, with the result that any benefit only accrues to a select few able to access clinicians willing to prescribe the drug.

 

[wigglethemouse]

The cost of an RCT is not that much compared to the many costs of not doing RCTs, including

Sure. But the money to fund an RCT has to come from somewhere. NIH staffers have stated several times in the last year or two that they think clinical trials are financially risky to fund in ME/CFS as they are expensive, and the outcome is likely poor when we don't know what pathways to target or have a biomarker. Perhaps this is why NIH funding has been lacking.

I know some have said on s4me that it need not cost much but other researchers dispute this. Who's right? I guess it depends, with some locations having an easier time than others.

I looked at the public financials for one unpublished small US study (not clinical trial) to test the applicability of an established test for another disease on a group of ME/CFS patients. No treatment. No clinical appointment. Just a blood draw and questionnaire I believe, followed by processing of the samples and interpretation of the results. $42,000 cost = $10,000 for the doctors time and facility, $32,000 for processing, Research coordinator costs covered by another fund - amount unknown.

For something like an Abilify RCT you need to pay for doctor time, tests, initial appointments, follow up appointments, medication distribution costs, admin costs, lab appointments and processing. And then what about adverse reactions - do you need separate insurance to cover that........ I'd love to know how Dr. Jarred Younger manages the financial aspects of his small clinical trials...........

Lets do a back of the envelope calculation regarding a theoretical study of Abilify at Stanford with 50 people.
* Safety labs would need to be done (e.g. CBC, CMP, Cholesterol ?). Somewhere like LabCorp has a list price ~$200. For example, say you want to test everyone before start, after one week, one month, and at end . 4 x 50 x $200 = $40,000 right away.
* I believe the list price for a doctors visit to the Stanford ME/CFS clinic is around $800. 3 visits x 50 * $800 = $120,000. So for lab tests and three visits we are already at $160,000.
* Add coordinator and admin costs.
* If you want researhers involved to run their own experiments on drawn blood you need to account for that.

Maybe you can negotiate lower prices with Stanford, that's what insurance does after all. Maybe you can figure out a way to have individuals insurance cover some of the costs. I honestly don't know what's possible. I'm sure they are looking at it.

Just for the record, I'm in agreement that I would like to see an RCT for all the reasons @Hutan lists and because sometimes patients do get worse with treatmants and this risk needs to be properly understood by physicians prescribing Abilify.

 

[mitoMAN]

@hmnr asg found this, I got access to full paper (see attached pdf)

Syk and Src-targeted anti-inflammatory activity of aripiprazole, an atypical antipsychotic. Yoo et al. Biochem Pharmacol (2018)

This is something we have to look at rather then the Serotonin/Dopamine targeting. My opinion. So seeking alterntaives cant relay soley on its neurotransmitter affinity. I have taken all kinds of Serotonin and Dopamine Agonists and Antagonists. Nothing ever helped like Abilify did.

 

[hmnr asg]

This is something we have to look at rather then the Serotonin/Dopamine targeting. My opinion. So seeking alterntaives cant relay soley on its neurotransmitter affinity.

I think you are right, otherwise other dopaminergic medications would have the same level of effectiveness, like paramipexole or others.

 

[jaybee00]

I think it’s dopamine—some people respond to dopamine agonists.

 

[mitoMAN]

Thinking of going up slowly to 1.5mg now. Seeing some good results after 14 days at 1mg!

Forgot to say I also take 200mg Celebrex which should increase my serum levels of Abilify a bit!

 

[Push Fwd]

Brex also works, even better, according to someone on the FB group. Caripraz might be hard to get an RX for because in doesn’t have an indication for depression— only schizophrenia.

@jaybee00 Which FB group is meant here? Is it the Abilify group or something else?

 

[jaybee00]

Yes

 

[Push Fwd]

Yes

Thank you. 😊
I asked for Martin because he is thinking about switching to Rexulti since Abilify doesn´t work anymore. We will have a look at the group soon.

The big question is if his desensitization to Abilify could potentially prevent Rexulti to work for him at the moment. The other concern is that it could also interrupt his drug holiday from Abilify and then he would have to start the break for 6 months again.
Is there anyone with expertise that has some thoughts about that? Maybe @Hip? I know that no one can answer this for sure but we would be happy about just some thoughts on this. 😊

 

[jaybee00]

Probably better to take a drug holiday/vacation for a while.

 

[hmnr asg]

Probably better to take a drug holiday/vacation for a while.

I am aiming for six months now.

 

[Hip]

The big question is if his desensitization to Abilify could potentially prevent Rexulti to work for him at the moment. The other concern is that it could also interrupt his drug holiday from Abilify and then he would have to start the break for 6 months again.
Is there anyone with expertise that has some thoughts about that? Maybe @Hip? I know that no one can answer this for sure but we would be happy about just some thoughts on this.

If we assume that dopamine stabilization is the mechanism by which Abilify benefits ME/CFS, then from what I can make out, the new brexpiprazole and cariprazine antipsychotic drugs are also dopamine stabilizers, see here:

Aripiprazole is a partial agonist of the D2R.

At high dopamine concentrations, aripiprazole lowers dopamine neuronal firing, while at low concentrations it increases dopamine firing.

At the time, this mechanism of action was called ‘dopamine stabilization’ because a single drug could increase or decrease neuronal firing as needed.

The newly approved brexpiprazole and cariprazine also utilize this D2 partial agonism mechanism.

So brexpiprazole and cariprazine might work in a similar way to treat ME/CFS.


Another interesting dopamine stabilizer is pridopidine (ACR16), which is also a sigma-1 receptor agonist (neuroprotective), but not yet available as a licensed drug.



It would be interesting to see ME/CFS patients who benefited from Abilify try very low-dose amisulpride instead, and see if they get the same benefits. Preferably before the benefits they get from Abilify disappear.

Unlike Abilify, amisulpride does not target adrenergic receptors, so does not have stimulant effects. I wonder if the stimulant effect of Abilify is somehow the cause of it stopping working after some months in some ME/CFS patients, as long-term use of all stimulants can sometimes lead to tolerance.

If it is the dopamine stabilization effect of Abilify which treats ME/CFS, then Abilify's stimulant effects would not be needed, and may actually be undesirable (because of the tolerance issue).

 

[Hip]

By the way, the original dopamine stabilizer drug that was tested on ME/CFS patients was amisulpride, rather than Abilify. This study from 2010 found that amisulpride 25 mg twice daily generally improved ME/CFS symptoms, and reduced fatigue and pain.

The paper also speculates a bit on the mechanism by which amisulpride ameliorates ME/CFS:

Low-dose amisulpride has been shown to bind preferentially extrastriate dopamine receptors [the extrastriate cortex is the part of the visual cortex] and, in schizophrenic patients, to increase frontal blood flow and to partially improve frontal cognitive functions

The relationship between amisulpride and frontal lobe activity and the link between frontal lobe functions and fatigue seem to suggest that the observed effect of amisulpride on fatigue levels could be mediated through prefrontal cortex activity modulation.

Interestingly, this study found that Abilify increases increases dopamine release in the medial prefrontal cortex and hippocampus.

 

[Push Fwd]

Thank you all for your reply! 😉
It's just so hard for Martin at the moment because he can't communicate with his friends and has to pace all day. So we are searching for something that could improve his situation while he is on drug holiday.

 

[hmnr asg]

I just wanted to update everyone on my appointment with Dr Bonilla at the stanford CFS clinic. Abilify worked amazing for me and then it stopped. I took a month long break and restarted and still it did nothing. I tried 0.5, 1 and 2mg and nothing worked anymore. I wanted to see if Dr Bonilla had some kind of solution. Well, he doesn't!

I told him that abilify doesnt work anymore and he seemed a lot more curious why i hadnt made an appointment before (two years had passed since my last appointment). When he finally let me get my point across he said its my fault because i pushed myself when abilify worked and then i crashed. I totally disagree with this. I didnt crash, I know what a crash feels like. I just lost all the benefits I had gained, but I wasnt experiencing PEM. The pill just stops working.

He then said that I should go back on the pill, because "even though you dont feel benefits, its helping you fight inflammation". So that's that.

He also wants to put me back on LDN and he also mentioned using plaquenil at some point in the future.
Also, when I asked for a refill of famvir (which had worked for me before), he said "no".

 

[jaybee00]

even though you dont feel benefits, its helping you fight inflammation".

No evidence for this inflammation claim. This whole post is disappointing.


Also disagree that you should go back on if it’s not working—doesn’t make any sense.

 

[leokitten]

@hmnr asg Bonilla is clearly horrible I would find another doctor. No ME clinician or researcher knows absolutely anything about how a treatment works in an individual or why it doesn’t work in another. It should ring alarm bells when they try to say otherwise.

And given all this when you say Famvir helped you in the past and it’s a drug with few if any side effects, so I have no idea why he cannot simply write an Rx for it. There is some research suggesting incomplete viral reactivation in some pwME. Good ME clinicians listen to their patients and if a treatment has low risk of harm then they should be open to individualized treatment. Isn’t this how Bonilla possibly found Abilify could work in some pwME?

 

[Zebra]

I just wanted to update everyone on my appointment with Dr Bonilla at the stanford CFS clinic.

Thank you so much for your post!

I have a follow up appt with Dr B in two weeks and I've been wondering what to expect. It's been a year since my last office visit.

Based on your experience, I guess he's going to be a bit fixated on the 1 year that has passed since my last appt at the clinic, but a lot of bad stuff has happened to me since then, and returning in one year is the best I can do this time around. I usually check in every 6 months.

The last time I e-requested a refill on my Famvir RX, he dropped it down from 250 mg x 3 per day to 250 mg x 2 per day without any explanation. I've been wondering if he's going to take it away from me altogether, even though it slowly, but surely, made a difference in a few neuro/nerve symptoms.

I've been taking LDN off and on in 2020/2021, It's difficult for me to know if the LDN is making a difference or if going to far fewer medical appts in 2020, due to pandemic, is why I feel a bit better, a bit more stable right these days.

When I last saw Dr B he was pushing Abilify aggressively. I staved him off at the time because I already take 3-4 medications that *directly* affect the central nervous system, which he was pretty cavalier about. I've been worried that he might drop me as a patient if I don't get onboard the Abilify Train. Do you think that's a possibility?

Thanks again for your update @hmnr asg!

 

[hmnr asg]

I've been worried that he might drop me as a patient if I don't get onboard the Abilify Train. Do you think that's a possibility?

I'm not sure if he will drop you. Of course I have no way of knowing that. He might nag you the way he did with me. But they absolutely are championing abilify now the way they were doing with antivirals before, so he might not take no for an answer.

 

[leokitten]

Hi everyone - I’m at the 1 month mark since I went to Abilify 0.5 mg. Things are going really great, I feel even better than when I posted my previous update.

I stay housebound on purpose to keep my physical and mental exertion in check, as well as not trying to do that much in my apartment. But life is really another universe from where I was a month ago. As you can probably tell since I haven’t been posting much, I am catching up a bit on life now (in my apartment) and am not chained to my bed like a zombie. I’m am spending time doing hobbies that I haven’t been able to do in such a long time that I can’t remember. Things like listening to music! (which would give me PEM if I listened to more than a few minutes before)

I haven’t gotten PEM or any other random symptom worsening or fluctuation. As I wrote before, I still keenly know and feel I have ME, though compared to my last update I feel it’s continued to feel more in the background and manageable . I know the improvements will likely stabilize at some time, but I feel currently there’s no need to increase from 0.5 mg.

Also, I’ve continued to experience no side effects.