Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Crosby et al. 2021

[wigglethemouse]

There is one warning that people don't always think about. If you are prescribed Abilify that will be noted in your medical record. Anybody viewing your record will see that you have taken an antipsychotic medication. In the US medical records are pulled for disability cases and reviewed so what you are prescribed has implications in the approval process and for coverage of your condition.

 

[Milo]

While this drug trial is preliminary and there is plenty of questions to ask and plenty of answers to get, there are some out there who are completely out of options, in horrible situations without health care. In that case, with a positive publication (not perfect) and considering that the risks for adverse events are low, and the drug in question is a pill (ease of use), and considering the absolute lack of any kind of effective treatment for ME, i would suggest that at least in some cases, off-label use would be he humane thing to do.

i am very much in support of further clinical trials that involves placebo control to examine the effectiveness, safety and dosage.

The unfortunate reality is that it usually takes 17 years in average to put a drug on the market. It may be less in the case of an already existing drug, but safety and efficacy for a particular disease needs to be determined.

 

[Hutan]

In that case, with a positive publication (not perfect) and considering that the risks for adverse events are low, and the drug in question is a pill (ease of use), and considering the absolute lack of any kind of effective treatment for ME, i would suggest that at least in some cases, off-label use would be he humane thing to do.

I guess I'm questioning whether we can view this paper as a 'positive publication'. The results don't exceed the response to placebos that we've seen in blinded ME/CFS trials. When I look at that report, I think, 'there is no response'. They seem to have taken out the 25% of participants with the worst results, and then shown that the remaining 75% averaged pretty minor improvements on subjective outcomes in an open label trial.

If the chances of this drug being truly useful for people with ME/CFS are very slim, the question is, is it the humane thing to do to suggest to people, many of whom, yes, don't have a lot of money or free health care, or people to support them, and all of whom are sick, that they should be making their way to specialist ME/CFS clinics to get hold of the drug? Is it humane for the people who have no way to do that to feel that they aren't doing all that they could to be better, or to waste energy trying to convince a doctor that they should try it? Or worse, to leave some people feeling that they have to experiment with the drug on their own?

And, at the community level, if the clinicians and researchers are busy looking at a drug that has a very low chance of helping, then they aren't busy looking at another drug that might be better. That might delay real improvements for the global community of people with ME/CFS.

What specifically in this report makes you feel that there is a positive result, @Milo?

 

[leokitten]

I think most everyone is adult and able to inform themselves enough to evaluate the pros/cons with their ME doctor and then weigh the personal decision on whether trial Abilify or not.

Given that it is a generic, cheap, easily accessible drug with a low risk of adverse effects at the dosage range then this helps too.

For those who prefer to wait for an RCT or further research to understand the putative role Abilify might play in ME pathophysiology or symptoms I totally understand and respect that decision too.

 

[Jaybee00]

Dear @Hutan

I honestly think you are being overly critical here...~50% reduction in fatigue and brain fog is pretty significant....

And, at the community level, if the clinicians and researchers are busy looking at a drug that has a very low chance of helping,

But this is your opinion...it is not mine.

There are several patient reports of people going from severe/very severe (like bed bound in dark rooms) to moderate on Abilify—not in 6 months but rather within a week or two of starting Abilify. I can’t cite these due to privacy issues. But if you marginalize patient experiences how are you any different from the BPS people?

Lastly, the major problem with Abilify won’t be with response it will be with tolerance/tachyphlaxis/poop-out—this is my opinion.

 

[James Morris-Lent]

Dear @Hutan
But if you marginalize patient experiences how are you any different from the BPS people?

It's not about marginalizing patient experiences. It's about demanding the production of reliable evidence.

BPS goofs have abused 'patient experience' to excuse their pseudoscientific research campaigns and unethical medical practices. Let us not allow 'allies' to take the same path.

If OMF is serious they can easily set up an RCT or preferably a dose-response trial. I don't see how the circumstances could be any easier and less expensive - it's a pill that's already a common, approved drug. I'm confident that any single one of our members could oversee this trial (but for the lack of stamina).

If the drug is truly beneficial, conducting rigorous, reliable clinical trials would make it available to however many millions of patients worldwide within several years; failing to conduct such trials would result in a very small percentage of patients being able to access the treatment at much greater cost. And then consider the scenario where the drug is harmful. I think the best course is obvious.

 

[dreampop]

IMO, the only thing you can say about this paper is Abilify may require a proper trial. It is not a paper that can be used to say Abilify treats me/cfs for reasons Trish and Hutan mentioned. I'm not impressed when authors use improvement in any side effect with self-reported outcomes. I'm a sap, but I always try to say somethign postive about a drug when I'm starting and all that even for a random symptom. The fatigue improvement is not "small" but it's the context that mediates the result.

I'm sure that when a medicine comes to treat me/cfs (if it ever does) it will have side effects. I'm glad people talk about them and make that information available in this context, as the drug is speculative. But, yeah, it is a very low dose.

Abilify, I don't know what I think, I have read the long thread on PR and Whitney's posts. They are interesting but I've read many such posts that go nowhere. Wasn't Bonilla pushing another drug a few years ago? Maybe an anti-viral? I can't even remember the name of it now.

Actually, I'm more interested in a palliative treatment that has side effects at this point. I think that's the best we will get in my lifetime, but I don't know if it's gonna be Abilify.

 

[Hutan]

I'm just trying to assess the findings, as we do for the BPS and other papers, and questioning if we can really say this is a positive result. Sure, it's not a negative result.

But, if the paper is not showing anything more than what might be expected with a placebo response in an open label trial with no controls, then I think we should say so, just as we would for a trial of CBT. I think there were 40% decreases in fatigue with the placebo in the blinded rituximab trial, and that result didn't benefit from the higher level of certainty that an open label brings.

Do we marginalise the experience of people who recover while receiving CBT when we say reports that are of a similar quality to this one don't show that CBT is promising for people with ME/CFS? Should we say nothing about the low quality of that evidence because people who improved while receiving CBT might feel marginalised?

 

[Andy]

Feedback from someone who reports being involved in this study.

https://www.reddit.com/r/cfs/comments/lc10p9/new_paper_on_low_dose_abilify_use_in_cfs/gly9xl6?utm_source=share&utm_medium=web2x&context=3

 

[Milo]

I guess I'm questioning whether we can view this paper as a 'positive publication'. The results don't exceed the response to placebos that we've seen in blinded ME/CFS trials. When I look at that report, I think, 'there is no response'. They seem to have taken out the 25% of participants with the worst results, and then shown that the remaining 75% averaged pretty minor improvements on subjective outcomes in an open label trial.

This current study actually did not test in a blinded manner. Therefore you cannot necessarily judge against a typical placebo. In my view it would vary depending on the specific cohort.

If the chances of this drug being truly useful for people with ME/CFS are very slim, the question is, is it the humane thing to do to suggest to people, many of whom, yes, don't have a lot of money or free health care, or people to support them, and all of whom are sick, that they should be making their way to specialist ME/CFS clinics to get hold of the drug?

Look, I am not convinced it will bring major improvement either, enough to send us all back to normal life. But someone pointed out to me that seemingly, the reason that Whitney improved is because of this medicine. And the patients i am connected with are desperate for anything. It is a drug that potentially A well informed GP could prescribe, the same way they prescribe LDN.

Is it ideal? No. Is it science-based? No. But for them, it may be the best thing to do. But this paper provides the little glimmer of home that a micro-dosage of an anti-psychotic drug may bring some relief to someone, and you know, who are we to judge?

My personal choice would not be to try this drug. But someone presented a different argument for their personal situation and it is not my choice to make and i’d know better than to argue that.

The status quo has got to change.

 

[Andy]

The status quo has got to change.

I agree, but my opinion is that it has to change on the basis of solid science providing good evidence, otherwise desperate patients could well end up wasting valuable energy, general health, time and money on treatments that don't work for them, and this study doesn't provide that [good evidence].

But this paper provides the little glimmer of home that a micro-dosage of an anti-psychotic drug may bring some relief to someone, and you know, who are we to judge?

Many things are reported to bring relief to some patients, such as GET, CBT, LP etc, and we judge those. We should have the same approach to all that are claimed as treatments, that way we will be able to make real progress.

 

[Jonathan Edwards]

Various members are suggesting that patients are able to make 'adult' rational decisions about this drug.
But as far as I can see even the authors of the study fell short on that. How on earth are patients going to know the odds? How is someone with ME going to know the right choice here if none of us have any idea, despite having the 'evidence' in front of us and being used to detailed scientific debate?

The status quo must change and what is needed is for patients to insist that 'ME expert' clinicians do proper trials on new treatment options rather than exposing people to risk without gathering any useful data. The argument about 17 years to drug approval is irrelevant since if these authors had done a controlled study in the first place we would already have an answer. A small but meaningful dose response study could easily be done at no more cost than hading out pills the way they have.

 

[Milo]

Agreed on clinical trials now, and good science now.
However we are fighting a culture of current practitioners who preach the CBT stuff and who do not have time to spend on research and clinical trials, let alone finding the money. The whole system, from where i stand, needs to be upgraded with a biomedical outlook instead of bio-psycho-social approach.

 

[Hutan]

Looking at all of the participants, the change in reported levels of fatigue went from an average of about 6 to 4, on an 11 point scale (0 to 10).

There might even have been a little bit of unintended bias from the clinicians. Records were only evaluated for patients seen twice or more. Without an intention to treat register, some patients might have excitedly tried it, found it didn't help and then not returned to the clinic. Even some of the patients who seemed to improve for a while and filled out a questionnaire recording the improvement may have got worse and been too sick or too demoralised to get back to the clinic to fill out another questionnaire noting the deterioration.

A small but meaningful dose response study could easily be done at no more cost than hading out pills the way they have.

I think the argument that would be made against that is that each person's dose is individualised, being titrated up and down according to symptoms. So, the theory is that each person has their own dosage response curve, that might possibly change from time to time. But the general idea still holds, they could have done a placebo controlled crossover design, given that Ablify is reputed to work quickly.

 

[Andy]

Agreed on clinical trials now, and good science now.
However we are fighting a culture of current practitioners who preach the CBT stuff and who do not have time to spend on research and clinical trials, let alone finding the money. The whole system, from where i stand, needs to be upgraded with a biomedical outlook instead of bio-psycho-social approach.

And I doubt anybody here would disagree with that, but just because the current system needs improving doesn't mean that we should be happy to encourage experimentation with unproven drugs on desperate patients outside of properly run trials.

 

[NelliePledge]

Two points about making general assumptions about other people with ME

1. people with ME active in forums, on Twitter aren’t the whole ME community - the understanding of science among people I’ve met in Facebook support groups is pretty much that of the general public

2. in the U.K. and probably to some extent in every country few people have access to anyone that can actually be described as an ME doctor.

 

[Jonathan Edwards]

However we are fighting a culture of current practitioners who preach the CBT stuff and who do not have time to spend on research and clinical trials, let alone finding the money.

That seems to confuse two different issues. Whether or not practitioners preach CBT has nothing to do with whether or not they have time to do trials. I know practitioners who recommend CBT but also make use of dog therapies. The issue of having time to do proper trials before handing out unproven drugs has nothing to do with what practitioners' time is taken up with. The whole idea that practitioners do not have time to do trials is to me a fallacy. I did trials in my 'spare' time while having to do research in the lab, organise the teaching programme and also run clinical service.

 

[Rain]

Not able to read the publication at the moment. Does it say what self-report form they have used? Never seen PEM being mentioned as a variable before. Have they made their own? Is that form public?

 

[lunarainbows]

While this drug trial is preliminary and there is plenty of questions to ask and plenty of answers to get, there are some out there who are completely out of options, in horrible situations without health care. In that case, with a positive publication (not perfect) and considering that the risks for adverse events are low, and the drug in question is a pill (ease of use), and considering the absolute lack of any kind of effective treatment for ME, i would suggest that at least in some cases, off-label use would be he humane thing to do.

I just wanted to say, I do not think it is right to say the risk for adverse effects are low. I know people keep saying this is a low dose. But if this is in fact working therapeutically for those with Severe or Very Severe ME, which would be no small feat, then by that same logic it would have side effects at that dose too.

And psychiatric medications and anti psychotic medication are not something to be taken lightly. They can cause tardive dyskinesia (and there’s no research to say it won’t cause that at low doses in those with Severe and very severe ME, who are already very sensitive to medication), which can be permanent - and anecdotally I was told by my autism counsellor (edit: and assessor) that some people with autism (who already have differences in brain functioning), have been permanently harmed by psychiatric and anti psychotic medications and so doctors need to be aware of possible harm even at lower doses if I am ever offered something as an impatient at hospital - in fact this is even in my notes and report somewhere. Given the similarities between autism and ME (in terms of sensory processing, and other neurological signs), I would not be so sure that there are not adverse effects in patients with ME, for those who are susceptible. For Whitney and for a few it seems ok, but we don’t know enough yet.

 

[Mij]

Has Abilify been used off-label for other 'fatiguing' type medical conditions?

I think most everyone is adult and able to inform themselves enough to evaluate the pros/cons with their ME doctor and then weigh the personal decision on whether trial Abilify or not.

This has nothing to do with being 'adult'. Come on now. Your ME doctor would have to truly understand what is occurring in your own particular case in order to even consider it.