Aripiprazole - Abilify

In the NICE guidelines, it is only prescribed in psychosis or mania in the U.K.

https://bnf.nice.org.uk/drug/aripiprazole.html

Even as an adjunct to depression meds - which isn’t listed in the guidelines - probably only if the other meds didn’t work, or perhaps if you saw a psychiatrist who would prescribe it off label. It doesn’t appear in the NICE guidelines above for Abilify.

I think most people in the the U.K. on Abilify probably do have schizophrenia. If I were to ever take it, if it was in my medical record, (since my medications are reviewed & checked every time I see a specialist / once in a while with the GP), it would definitely be heavily questioned why I was on antipsychotic medication. Especially when there is no proper research backing this up, nothing in the NICE guidelines about it, no firm understanding really on what dosages or why it helps ME, it wouldn’t be properly monitored by anyone as to side effects, dosages or interactions, and I am certain I wouldn’t find a consultant on the NHS willing to back it up either.

 

Yep, so exactly the same guideline as in Finland. The only reason I point this out is that for people reading this thread, they shouldn't think they can just walk into the doctor's office and complain about a little depression and hope to get Abilify. The medical records are the other issue (although that access can be hidden I suppose, at least in my country's software). The third thing to point out is that you probably don't want to make up that you have psychosis or are hearing voices if you are not, as there is a small, but real risk that you get sectioned involuntarily.

 

Dr Shepherd's comments look to me to be nuanced and appropriate.
My own experience with psychotropic drugs is that typically half a dozen are tried that make people worse before anything is found that helps. For people with lethal psychiatric disorders like schizophrenia or psychotic depression you have to try them but otherwise I wouldn't go near them.

But then that is just my personal experience, not a randomised trial!

 

I’ve been pretty excited and vocal on PR about it, just to say it here too that I’m looking forward to trialing low dose brilaroxazine (RP5063 aka oxaripiprazole) for ME as a replacement for Abilify when it gets approved if there’s nothing better than low dose Abilify by 2025.

It has an even better binding profile than Abilify with few to no off target effects. So far in phase 1 and 2 trials for schizophrenia and on normal adults it has shown no endocrine or metabolic side effects which will be a breakthrough in the antipsychotic space:

Reviva Announces Full Details of Positive Phase 2 Clinical Trial Results for Acute Schizophrenia (brilaroxazine)

Reviva starting brilaroxazine phase III trial for schizophrenia in mid-2021

 

As I see, no one of critics has addressed that the dose is far lower in ME than for psychiatric use.
Far lower normally means that side effects should be more seldom.

 

Yes i was prescribed it in the uk as an add on, to my anti depressant, for depression.
I think you have to put the potential dangers of using it into context. I lot of meds can cause severe side effects and are used without any concern at all. I was given a drug for stomach function that could cause a permanent twitch.
I noticed on the packet it says one of the uses for abilify is irritability in autistics. I would say that's a lot less reason to use it than M.E.

 

Here’s the paper on the phase 2 clinical trial results for brilaroxazine. Abilify is also an arm in the trial (powered for sensitivity not efficacy).

If not clear from my previous post, I think low dose brilaroxazine could be a drug worth trialing as a potential treatment for ME. The following papers provide a lot of useful information for people wanting to learn more about this drug.

Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder

 

Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy Volunteers and Multiple Doses in Patients with Stable Schizophrenia

Pharmacokinetics of RP5063 Following Single Doses to Normal Healthy Volunteers and Multiple Doses Over 10 Days to Stable Schizophrenic Patients

 

Brilaroxazine (RP5063) is also being trialed by Reviva for PAH because of its effects on serotonin receptors.

 

This paper has useful pharmacological and kinetic information:

RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia

 

For those who are new to this thread and reading about Abilify for ME thinking, "could ME be a neuropsychiatric disorder?", the answer is no. It's as much a neuropsychiatric order as I would say lupus, multiple sclerosis, Parkinson's and dementia are, diseases that are physiological but dramatically affect brain function as well.

As a person for whom very low-dose Abilify appears to have significant efficacy, I can tell you just by how I feel - and I know this is a subjective assessment, but those of you with ME reading this know exactly what I'm talking about, the disease and symptoms have a constant, non-stop, every second of the day effect on your entire body so you intimately feel what is going on and develop a pretty good barometer - the way ME is currently interacting and negatively affecting my body with Abilify and the difference between pre-Abilify is that Abilify does not feel like it targets whatever the root driver(s) of ME are in me (I sincerely feel that), but it seems to have some huge counteracting effect on some of what the root driver(s) are dyregulating and affecting.

My particular case too I feel my ME barometer works pretty well now (but not long ago) because during the first couple years I had way more varied and fluctuating symptoms and immune activation but as the years have gone by fluctuations subsided and symptoms have concentrated to this core set that just never got better and were slowly making me worse. So I don't have a lot of ME "noise" anymore affecting how well I can feel what the disease is doing to me on a daily basis, if that makes any sense.

If we just assume for the sake of it that the reason Abilify significantly improves some very important core ME symptoms in a subset of patients is because of it's dopamine and serotonin system stabilizing effects, then the root driver(s) of ME in this subset are dramatically affecting dopamine and serotonin system function in a very negative way, therefore causing some of the core symptoms of the disease, i.e. PEM, fatigue, neurological symptoms, light and sound sensitivity, etc. Abilify dramatically reduces these, even makes them completely go away, or makes it much more manageable that you can be more than just a suffering zombie with severe illness in bed 24/7 unable to sleep or truly be alive.

I think this is a big deal because at least for me I feel this is the beginning of a much needed potential door opening towards understanding something about this terrible disease. I believe even the rituximab saga didn't help nearly as much with some initial clues as Abilify, just my personal opinion. That's why I hope for in future better dopamine-serotonin system stabilizers with fewer off-target side effects, because I don't see anything else promising coming down the pipeline.

I'm currently not feeling very hopeful that there will be some huge mechanistic and targetable breakthrough with a new drug treatment that will make everything significantly better for most pwME. I feel its going to be as it has been a chipping away strategy of taking a number of drugs and possibly supplements that have shown some clues in research or anecdotally to have some effect and that each will have some additive effect in a subset which brings us to a threshold where we can live some kind of life.

 

I have much of the same thoughts and experiences as leokitten. I also have had a steady decline, unless I found something that works, ketogenic diet last year, and Abilify this year.
I wrote this when I entered this thread, that answer Trishs question,

Good to hear you are still having effect, @leokitten. I have too. I am trialing different doses, right now my working theory is that my sweet spot dose is 1mg/day. I am a little below that now and not as good as I was when the doses was higher. But they should not too high either, there was both poop out and side effects at doses higher than 1,75mg.

edit; I also see the need to be catious about what is working and not. Living in Norway where the Lightning Process is a nightmare for us, it is inevitable that the successstories of LP is getting very much attention and can’t be overseen or overlooked, so when saying something is having effect, it is kind of not more valuable, in principle, than the LP stories. Which does not represent the majority of ME patients, so maybe this doesn’t either.

 

The biggest difference by far I can remember, and this is a huge difference - is with the ketogenic diet after the first couple weeks, where I felt OMG I'm in remission, if I physically or mentally exerted to the same level I can now do on Abilify I would crash. Keto would make the crashes pretty short and recovery fast for the first few months, but I would still crash from overexertion nonetheless. I would also increasingly get the intense carb hunger signaling that I was overexerting and going to crash very soon even before keto, but keto made that stronger once it started to slowly not work as well. With Abilify (and moclobemide) nope none of that.

I've been on Abilify over 3 months now and haven't crashed once or had any really significant PEM, and I've exerted the same or sometimes more than when I was on keto. It's like Abilify just prevents it from happening or drastically reduces it.

If the reason Abilify is able to do this has nothing to do with the effects it has on cellular metabolism (it has a negative effect on sugar metabolism, but counterintuitively with ME who knows that could be pushing ME metabolic dysfunction to normalize somehow), then this is one step towards proof that, at least for a significant ME subset, PEM and other symptoms are neurological and at the end of some pathway driven by dysregulation of dopamine and serotonin systems in the brain.

Another difference is that Abilify had normalized my sleep! Or maybe the moclobemide with Abilify is the combo making the difference here. But the over two months I was on moclobemide before starting low dose Abilify I didn't have any improvements in sleep.

For the first month or so Abilify made falling asleep more difficult, but once I got through that phase the payback on sleep has been really good. I wake up at a normal early time now and get truly tired, even yawning and watery eyes, at the right time at night. Everything shifted forward back to normal instead of ME falling asleep at 2-4am because of intense wired but tired and other symptoms.

I still need to take my regular sleep meds which I've been cycling and taking for years, but for some reason the Abilify (or together with moclobemide) makes them work much more effectively with a lower dosage, and the important thing is that they never fail to work. And I fall asleep fairly quickly after getting the wave of tiredness at night, similar to before ME.

Before Abilify, multiple times a week (depending on exertion that day or days before) I would not be able to fall asleep or get control of the night symptoms no matter how much I tried to knock myself out in desperation with sleep meds.

The keto diet did help with sleep too, particularly in the beginning along with the other symptom improvements. I felt a significant improvement in the wired but tired symptom at night, but it didn't normalize my sleep time or help nearly as much as Abilify has (and possibly moclobemide).

 

One aspect of my ME that Abilify appears to have little effect on is my suspected mast cell activation problems in my gut and lower abdominal skin at night.

I’ve had this ME-related symptom making everything else worse and causing me anguish since 8-10 months into the illness. I don’t know why not until more recently did I try to pinpoint that these symptoms appear to be mast cell related given other people’s experiences.

Abilify appears to help my brain overcome or counteract the neurological effects this has irritating and shooting up from my gut through my nervous system at night (it literally feels like that) but it doesn’t seem to effect whether I’m going to get it or not.

Given the possible mechanistic hypotheses I’ve mentioned regarding Abilify it would make sense, it doesn’t seem to have any effect on the immune system outside the brain in any way.

 

@leokitten
YOu write: "...
the disease and symptoms have a constant, non-stop, every second of the day effect on your entire body so you intimately feel what is going on and develop a pretty good barometer - the way ME is currently interacting and negatively affecting my body with Abilify and the difference between pre-Abilify is that Abilify does not feel like it targets whatever the root driver(s) of ME are in me (I sincerely feel that), but it seems to have some huge counteracting effect on some of what the root driver(s) are dyregulating and affecting."

Your sentence is very interesting. Abilify you say, a) does not target the root drivers, but b) seems to be counteracting some of what the root drivers are affecting.

My daughter also says there is not one second of the day or night where she is free of ME, but she says the primary problem is exertion intolerance--mental or physical or emotional exertion. Because there is constantly payback. Therefore, she is unable to do much--not because her body can't move or think, but because these exertions, even the most minimal, bring on PEM--or crashes, which are hell on earth.

Thus, Ron Davis, called this illness SEID.

Would you say your situation was like my daughter's? Or different?

So, is it that Abilify stretches that envelope, so that you can do things, exert, and not get payback? (In other words, it is not a cure but raises the baseline??)

I am reading the FB forum on Abilify and there are so many side effects that people are writing about. And withdrawal effects too when someone wants to stop.

The other thing is, if this drug is helping with 'exertion,' why aren't the researcher trying to figure this out more. (Rhetorical question,I know.)

 

I can't answer your other questions, but figuring out why and how Abilify seems to be beneficial to (a subset of) pwME is an area of active investigation at the OMF. Ron mentioned it a few times in update videos and presentations.

 

I knew that trying to be as detailed as possible would probably get confusing. It’s really hard sometimes to describe clearly how this illness changes or feels.

Imagine this, on Abilify my skin changes haven’t improved anywhere towards normal, my hair changes haven’t, my subcutaneous tissue and muscle haven’t improved back towards how they were before ME, and other clear physiological symptoms and signs in my body (not brain) that changed very suddenly after getting ME haven’t improved back, like eg the suspected mast cell flare ups too.

Whatever fundamental and totally screwed up mechanism(s) causing these issues that are at the core of my ME are also causing some pretty major neurological problems and symptoms too, which only after taking Abilify I realize that wow ok whatever ME is messing up in my brain is a big downstream driver of debilitating symptoms, PEM, fatigue, light and sound sensitivity, etc.

Abilify feels like it’s counteracting whatever is happening at the end of these dysregulated pathways in the parts that are affecting my brain. It’s appears to be silencing or strongly dampening it.

And after over 3 months on it I feel more confident in saying that it’s not just covering up overexertion signals and damaging myself without realizing it, otherwise it would’ve stopped working by now or I would be worse off, like I felt with keto that the crashes were making me worse and it was giving me more of a false sense of improvement after a couple months.

Hope this makes more sense.

 

Yes, exactly, and by A LOT.

 

I am reading the postings on the FB page. I am very concerned to read that a few people are saying they or a family member now have 'permanent damage' from this drug, in the form of tremors, and other problems. I just don't know what to make of a drug that can do this sort of thing. Of course, the other issue is that as there is no diagnostic test for ME, it is hard to know if everyone trying this drug actually has ME, or some other malady. I just don't know what to think.