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

leokitten said:
Just like @cassava7 said about POTS where the drug evidence base is somewhere in the middle and nowhere near where it should be for the level of prescribing by doctors and use by patients. But I don’t see the level of skepticism and risk aversion here on S4ME regarding mestinon, midodrine, etc. for POTS, even though there actually quite little evidence that they work well. This is just one example there are others.
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There are tests for POTS to determine whether a patient responds to a medication. They can be properly monitored.

What tests were done for pwME taking Abilify? What is ME? It's a shot in the dark.
 
There are several medications that can improve POTS symptoms and are supported by small prospective studies or retrospective case series. The patient can be SAFELY monitored.

From the OP original link:
Results: Of the 101 patients taking aripiprazole, 75/101 (74%) experienced an improvement in one or more categories: fatigue, brain fog, unrefreshing sleep, and frequency of post-exertional malaise (PEM) episodes, or “crashes.” Twelve individuals (12%) had no observable difference in symptoms at the maximum dose of 2 mg, and 14 individuals (14%) reported worsening of symptoms or onset of side effects that led to discontinuation of the drug (Fig. 1).

There is not biomarker for PEM. They are referring to PEM and fatigue interchangeably to treat fatigue.

Where is the evidence that pwME have a 'neuroinflammatory condition'?
 
A year ago I showed a psychiatrist a list of the various studies being done on ME (with very short 3 line summaries). He flipped through the pages and said: Holy smokes, they are all over the place. They just don't know what is going on.

I think that it might be useful for Stanford, if they are going to do more Abilify studies, to bring on board some psychiatrists who have experience with this drug.

In our experience, various drugs helped very briefly: hydrocortisone, fludrocortisone, midodrine, HGH, oestrogen, and many others, but nothing lasted. Mestinon was awful and not tolerated. Everything just brought massive side effects and whatever little temporary gain there was petered out. ( The CFS/ME doctors in the usa have lots of experience trialing these drugs on patients who are so desperate and who are suffering abominably.) But in our case the disease just marched forward like Charlemagne's army.
 
Trish said:
The suggestion that we would be against a medication that was originally developed for a psychiatric condition, but is used for a different effect in a different dosage for ME has, as far as I can see, no foundation, and some might consider it offensive.
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Correct—I agree. Which is why I was put-off by the somewhat overly-critical sentiment coming from this thread about a med originally developed for psychiatric conditions that might be repurposed for MECFS. Fine to criticize the shortcomings of the published study. But not fine to criticize the concept that Abilify might be useful in treating the symptoms of MECFS. If you think the study is flawed then you can’t make any conclusions one way or another. That means you can’t conclude that it has a very low likelihood of helping patients.

MECFS is a horrible disease that leaves many people bedbound in dark rooms. If you’ve already made up your mind that the many people who have dramatically responded to Abilify are placebo effects and conclude that there is no reason to proceed with further studies, then you may not be helping the pwmecfs.
 
Jaybee00 said:
MECFS is a horrible disease that leaves many people bedbound in dark rooms. If you’ve already made up your mind that the many people who have dramatically responded to Abilify are placebo effects and conclude that there is no reason to proceed with further studies, then you may not be helping the pwmecfs.
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Pardon me for interfering, but I did not get that impression from Trish at all. They are just discussing the cons of the retrospective study, which is great - thats the point of this site no?
 
Going back to Abilify and this paper, have we ever seen any other treatments have such a positive effect on so many very severe and severe pwME?

I know that very severe or severe pwME are not totally immune to placebo effect, just wondering when you are so very sick every second of the day if it would be harder to mount a placebo effect.

Did RituxME have significant numbers of very severe and severe ME cases? Were there placebo effect differences depending on ME severity level?
 
Jaybee00 said:
If you think the study is flawed then you can’t make any conclusions one way or another.
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That's not always true. The PACE study was flawed, but we can still conclude that it provides fairly good evidence that CBT and GET do not cure CFS, or even markedly improve it. The Ablify study had a number of flaws that worked to amplify positive outcomes and yet the reported findings were of relatively minor average changes in subjective outcomes and very little impact on people resuming work. To me, it looked like there was evidence of a low likelihood of Ablify substantially helping a majority of people with ME/CFS. Of course, it's possible that a minority were truly greatly helped.

I do hope a proper study will be done. It's just for me, on the basis of this study, at least as it is reported in the paper, if I was prioritising funds to be allocated to research in order to bring the greatest benefit as quickly as possible, Ablify would not be my highest priority. It has nothing to do with what kind of drug it is, or even its side effects.

However, I have not personally seen people with ME/CFS seem to respond in remarkable ways to Ablify - for sure, if I had, I would be very keen to see more research.
 
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leokitten said:
Going back to Abilify and this paper, have we ever seen any other treatments have such a positive effect on so many very severe and severe pwME?

I know that very severe or severe pwME are not totally immune to placebo effect, just wondering when you are so very sick every second of the day if it would be harder to mount a placebo effect.

Did RituxME have significant numbers of very severe and severe ME cases? Were there placebo effect differences depending on ME severity level?
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They didnt look at very severe. I think in cyclo they looked at severe, but they did not have much effect I think. I think the other intervention were one have seen very severe report huge improvement is Lightning Process, hence why skepticism is warranted always for retrospective studies, although the method there explicitly involves lying about your symptoms

Edit: to answer your question, no i dont think many interventions have. And thats what made me interested initially.
 
If a RCT trial demonstrates a 30 or 50% decrease in fatigue for Abilify that would be huge and would almost certainly earn Abilify a prescribable (sp) indication for MECFS. And would be fantastic for patients!

So my opinion is that this should be among the highest priority areas of research because it is a low hanging fruit. But duration of response also needs to be looked at in addition level of response.
 
Jaybee00 said:
If a RCT trial demonstrates a 30 or 50% decrease in fatigue for Abilify that would be huge and would almost certainly earn Abilify a prescribable (sp) indication for MECFS. And would be fantastic for patients!

So my opinion is that this should be among the highest priority areas of research because it is a low hanging fruit. But duration of response also needs to be looked at in addition level of response.
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As long as they design the damn RCT properly! Not like the OSU6162 RCT where they gave the drug for only 2 weeks!

Let’s get the trial dosages right, the treatment time course right, and physical and cognitive endpoints right! I think we pwME collectively sigh and shake our heads as much or more than any other illness community when reviewing research on our disease.
 
Jaybee00 said:
Which is why I was put-off by the somewhat overly-critical sentiment coming from this thread about a med originally developed for psychiatric conditions that might be repurposed for MECFS. Fine to criticize the shortcomings of the published study. But not fine to criticize the concept that Abilify might be useful in treating the symptoms of MECFS. If you think the study is flawed then you can’t make any conclusions one way or another. That means you can’t conclude that it has a very low likelihood of helping patients.
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Given that it has been suggested that I have been too negative about Ablify, I want to try to explain my reasoning:

Over a quarter of the participants either didn't improve or worsened for every outcome, or had side effects that led to withdrawal. Think about that - coming to a specialist ME/CFS treatment centre for multiple visits and reporting not improving, not even a little bit, on any of fatigue, brain fog, unrefreshing sleep, or frequency of PEM outcomes. These people aren't just receiving Ablify - they are also being treated with a range of other medications and presumably being given good advice on how to manage their illness. Many people will have been motivated to seek treatment when their illness was worst and would improve naturally with time anyway.

With that context, the average reported improvement in fatigue from the 75 people in the 'responder' group doesn't seem very remarkable. Only 66 people contributed fatigue data from the 75 - it seems likely that there was a cherry picking effect here and the 9 'responders' who didn't contribute fatigue data had a worse fatigue outcome than those who did. The average change in reported fatigue in the 66 people from the responder group was from around 6 to around 3 on an 11 point subjective scale. So - two thirds of the participants in the study reported an average of an improvement from 'somewhat bad fatigue' to 'not too bad fatigue', with some no doubt doing better, and some doing worse. It's likely that more than one third of 101 participants either didn't report on fatigue, or reported no change or a worsening in fatigue. This is despite all the other care that they were receiving at the clinic and the powerful incentive to feel that their decision to go to the clinic was worth it.

And that's just the fatigue outcome. The numbers of people contributing data to results vary, and there are things that aren't clear.

There's nothing there suggesting to me that Ablify did anything remarkable or even anything at all over and above what time, good advice on pacing and perhaps other drugs for pain and sleep would have done. But, I can't rule out the possibility that Ablify did significantly help a subset of people.

I support a blinded trial, as I do for any drug that clinicians are suggesting is a treatment for ME/CFS. I continue to believe that encouraging people to take Ablify outside trials is not warranted by this data.

Just for the record, I am not negative about the chances of Ablify being the treatment we are all hoping for because it's a psychiatric drug. I have a problem with the BPS idea that it is my and my children's lack of will to get better that keeps us sick. I don't believe that psychiatric illnesses, for example, schizophrenia, are caused by a lack of will to get better either, I think there are biological causes - and so I have no problem at all with a drug that successfully treats psychiatric illness being proposed as a treatment for ME/CFS.
 
Hutan said:
Just for the record, I am not negative about the chances of Ablify being the treatment we are all hoping for because it's a psychiatric drug. I have a problem with the BPS idea that it is my and my children's lack of will to get better that keeps us sick. I don't believe that psychiatric illnesses, for example, schizophrenia, are caused by a lack of will to get better either, I think there are biological causes - and so I have no problem at all with a drug that successfully treats psychiatric illness being proposed as a treatment for ME/CFS.
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I agree wholeheartedly with this, the BPS folks give the rest of psychiatry a bad name, because at least here in the US psychiatry believes and there’s an ever increasing mountain of evidence to show that psychiatric disorders have a neurobiological basis. There is also a very fuzzy line between neurological and psychiatric disorders/diseases. So much overlapping pathophysiology and symptomatology.
 
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Hutan said:
Over a quarter of the participants either didn't improve or worsened for every outcome, or had side effects that led to withdrawal. Think about that - coming to a specialist ME/CFS treatment centre for multiple visits and reporting not improving, not even a little bit, on any of fatigue, brain fog, unrefreshing sleep, or frequency of PEM outcomes. These people aren't just receiving Ablify - they are also being treated with a range of other medications and presumably being given good advice on how to manage their illness. Many people will have been motivated to seek treatment when their illness was worst and would improve naturally with time anyway.

With that context, the average reported improvement in fatigue from the 75 people in the 'responder' group doesn't seem very remarkable. Only 66 people contributed fatigue data from the 75 - it seems likely that there was a cherry picking effect here and the 9 'responders' who didn't contribute fatigue data had a worse fatigue outcome than those who did. The average change in reported fatigue in the 66 people from the responder group was from around 6 to around 3 on an 11 point subjective scale. So - two thirds of the participants in the study reported an average of an improvement from 'somewhat bad fatigue' to 'not too bad fatigue', with some no doubt doing better, and some doing worse. It's likely that more than one third of 101 participants either didn't report on fatigue, or reported no change or a worsening in fatigue. This is despite all the other care that they were receiving at the clinic and the powerful incentive to feel that their decision to go to the clinic was worth it.

And that's just the fatigue outcome. The numbers of people contributing data to results vary, and there are things that aren't clear.

There's nothing there suggesting to me that Ablify did anything remarkable or even anything at all over and above what time, good advice on pacing and perhaps other drugs for pain and sleep would have done. But, I can't rule out the possibility that Ablify did significantly help a subset of people.
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Maybe I missed something in the paper, but I don’t think it was cherry picking but that they were missing data for some cases.

I would agree with you here IF it could be said that the retrospective analysis endpoints were robust. They weren’t in my mind which really makes it hard to judge the findings, meaning it could’ve been worse or better had they used more robust measures.
 
Hutan said:
I'm not suggesting that it was deliberate cherry picking, and maybe that's not quite the right word, but that the effect of such a significant amount of missing data was probably to produce a more positive result.
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Yes, cherry-picking is mostly not deliberate. Cherries often pick themselves. The manky ones have already dropped off the tree. The underripe ones refuse to be picked. It's cherry picking.
 
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