Aripiprazole - Abilify

You have to remember when reading research or other reports on Abilify that none of the existing research on the drug is based on very low dosages between 0.25 - 3 mg / day. It’s just is a very different drug at those dosages so doubtful what is described even applies anymore.

 

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This is why it is urgent to get a diagnostic test asap. How can we be certain that everyone has the same illness? Some folks respond to Abilify, some to steroids, some to diet or to mould avoidance, and some respond to absolutely nothing. Without a test, we cannot know who has what.

(Just as an aside: during the Covid lockdown, the traffic in Montreal virtually came to a halt. The air became wonderfully breathable. The same thing happened all over Canada. I noted that a few people with ME (whom I am in touch with) suddenly started to feel a touch better. Does this mean that cleaner air is the prescription....)

 

I recall hearing something about the discovery of a potential mechanism for the action of lithium in bipolar disorder. The suggestion was that lithium modifies the shape of a protein and that leads to an improvement in bipolar symptoms.

Immunoregulatory drugs successfully treat autoimmune NMDA receptor encephalitis - it presents like schizophrenia/epilepsy.

I suspect future generations will look back at the dark ages (i.e. now) before we understood the biomedical basis for "psychiatric" diseases - pretty damn convenient label i.e. "psychiatric" diseases.

@Jonathan Edwards has said that he believes that all diseases are physical - I like that - https://www.s4me.info/threads/nice-...-10th-november-2020.17687/page-13#post-302003

 

The more real research psychiatry has done over the years the more they uncover that many psychiatric disorders have potential neurobiological bases. They are disorders of the brain not the mind.

This was an interesting article:

The wall between neurology and psychiatry. Baker et al. BMJ (2002)

 

There's a Christmas post on MEAction Global by Janet Defoe/Whitney re Aripiprazole/Abilify - OMF are looking at the underlying mechanism for Aripiprazole/Abilify

 

They also need to look at the tachyphlaxis (poop out) mechanism and how to overcome it.

 

https://med.stanford.edu/content/dam/sm/dbds/documents/data-studio/abstract.20201118.pdf

Retrospective data analysis of Abilify plus plans for a randomized clinical trial. 74% of patients reported symptom improvement.

@Jonathan Edwards —your critical thoughts?

 

We need something more professional than this to get anywhere. Why is a retrospective review being done rather than looking prospectively? If patients are assessed retrospectively we need details of the indications for treatment, the nature of the referral pattern for the clinic involved, the full list of their diagnoses and so on. We do not even know if these patients were treated for depression or for CFS.

74% reporting improvement is probably what one would expect from an inactive agent (even without expectation bias 50% are likely to be better by chance and 50% less good). The drug may be of value but this account does not help us.

The questions raised suggest that the investigator does not really understand trial design. The question about statistical significance is meaningless unless a clinically significant effect size has been decided. There is no mention of any trial design in fact, despite asking if it is the best trial design.

 

I'm sure psychiatric drugs create side effects aka symptoms that could be mistaken for new diseases in a patient. So, it doesn't seem to me that altering the presentation of a disease or modifying a disease would be impossible. If it did happen then I would guess it was an accident. I doubt that improving chronic diseases is something Big Pharma ever does deliberately.

 

May I ask then, in pwME why do we not see even remotely close to those percentages for any drug, procedure, supplement, etc? If you say placebo effect is typically that strong? In pwME interventions historically have anecdotally shown benefit (whether placebo effect or not) in zero or very small percentages of patients. Let’s assume that the Stanford ME clinic is diagnosing patients for ME using best practice clinical criteria, which is not a big assumption they are a well established and regarded ME clinic.

 

Do you have any evidence for casual retrospective record reviews showing less than 74% of cases reporting improvement on at least one of several endpoints? I think you are thinking of rates of improvement in prospective trials according to predefined criteria. Even in the PACE trial control group more people had improved scores than worsened scores - so that's probably about 75% improving after getting not even a placebo - just 'standard medical nothingness'.

If you record the weather on one day and then record the weather on another and look to see in how many cases at least one aspect of the weather is better what percentage would you expect. It is likely to be 60-70%.

The reputation of a clinic is of no real interest if investigators do not understand basic rules of obtaining reliable clinical trial evidence.

This is why I keep saying that activists should be banging on the doors of 'top ME clinicians' and asking them to start doing clinical research properly.

 

Yes but if people are saying they are getting positive effects from 0.2 mg and such microdoses, assuming those effects are real, then they can also get harmed by the same dose. Published literature is irrelevant.

 

Maybe we are assuming too much of the intent of Stanford’s retrospective chart review, it could very well be to look at the data they have before going forward with a trial, whether open-label or blinded placebo controlled.

From what it looks like OMF and Stanford might do this and did the retrospective review with that in mind, especially since it doesn’t take a ton of work comparatively to do such a review, even though you cannot trust the efficacy evidence but there was other information gathered as part of the review that they wanted to look at.

 

Patients with comorbid depression should be excluded from a trial of aripiprazole because this is a recognised adjunctive treatment for depression.

 

It could also very well be that on the Zoom meeting they discussed far more details as it was a meeting for clinicians and investigators. I wonder if we can get more information from the meeting.

 

Nobody is assuming anything other than what you suggest. That is obviously what they have done.
The problems are:
1. That they should never have been in the situation of reviewing 70 cases of CFS treated with Abilify without having started a trial and if the cases were treated for something else then I doubt we can make anything of the findings.

2. If they want to make use of this information in a discussion session with a view to a trial then they need to be a bit more professional about how the data are gathered and presented.

I feel uncomfortable being critical other clinical groups. However, I am constantly reminded of the tweet from Michael Sharpe where he accused me of being 'disloyal' to fellow colleagues. That made me realise that my only loyalty was ever to the patients, never to colleagues. I am critical because to do anything else would be disloyal to patients who need to know if research that is being done on their behalf's below basic minimum standard.

 

I think it depends a lot on how the trials were set up though. A retrospective study of LDN in ME/CFS (article) showed almost the same number (73.9%) of patients improving, but we know LDN is no miracle drug in ME/CFS despite lots of patients having trialed it. I think it's very much conceivable that you'd get such a number without the drug itself having any positive effects. Having said that, I hope they go forward with doing more robust studies with Abilify if they have reason to think it helps.

 

Here’s the answer you’d get: “we don’t have the money for that. No funding. Clinical trials are very complicated. It would take too long.” Chances are, these physicians do not have the relevant training and support to conduct clinical trials, for many reasons, including the fact that they never did it before, and they are not necessarily supported by academic institutions. And that explains why so many drugs are offered off-label.

A medical specialty would solve many problems (but not all), along with the commitment from funding and academic bodies to solve the problem.