Abilify- Stanford Clinic Patients

[leokitten]

This will probably be controversial but for me personally, I almost wish I hadn’t started abilify. It is too depressing to have something work for about a month and then slowly go back to the way I was before. I also took up some hobbies that now I am pretty much unable to do once again.

I agree a month or two is way too short, but 7 months I was able to do a lot of one offs that needed to do and couldn’t before, was able to move cities to a cheaper place as well as many more things I was able to accomplish that I don’t regret.

 

[5vforest]

I agree a month or two is way too short, but 7 months I was able to do a lot of one offs that needed to do and couldn’t before, was able to move cities to a cheaper place as well as many more things I was able to accomplish that I don’t regret.

Yes, want to be clear that I’m speaking for myself and my situation only. I know from reading how important it was for you and I’m super happy you got that period of time where you felt better

 

[gm286]

@leokitten just had to mention how very, extremely close (one to one really) your description of your sleep as ME symptom is — how copy-paste it is to mine, and how similar our reaction to Abilify was (for sleep). Your description of it fixing your sleep was exactly my same experience… The first (and only) two weeks that it kicked in and worked, exactly like you say, got me into a pattern of healthy and replenishing wake / sleep, the same kind I had consistently pre-ME.

 

[leokitten]

@leokitten just had to mention how very, extremely close (one to one really) your description of your sleep as ME symptom is — how copy-paste it is to mine, and how similar our reaction to Abilify was (for sleep). Your description of it fixing your sleep was exactly my same experience… The first (and only) two weeks that it kicked in and worked, exactly like you say, got me into a pattern of healthy and replenishing wake / sleep, the same kind I had consistently pre-ME.

It’s definitely doing something very real here, whenever (hopefully) they figure out what causes the unrefreshing sleep and disturbances I know they will see why Abilify helps tremendously here.

I know that a few ME reviews like the one in the recent Mayo Clinic consensus recommendations (https://www.mayoclinicproceedings.org/article/S0025-6196(21)00513-9/fulltext) say it’s due to reduction of heart rate variability in ME, but is this really proven and settled? I thought not

 

[J.G]

0.75 mg. I didn’t want to go any higher because I think that would just buy some time until the same tolerance or do nothing at all.

Makes perfect sense. I'm on 0.2mg and hesitant to increase for the same reason - I'm looking to drag out Abilify's effectiveness for as long as possible. A gentle rolling curve rather than a sharp rise and fall, so to speak.

I've been on Abilify now ~1 month, and already it's working wonders for mental clarity, cognitive stamina, sleep quality (good-bye night sweats), and subjective well-being. Word finding is so much smoother. The constant feverish feeling is much diminished. And funnily enough I recovered some of my sense of taste and smell, which I hadn't realised was partly gone. Before anyone asks - no, I didn't come down with (long)COVID; been sick 11 years.

I'm fully expecting the positive effects to wane sooner or later, so I'm taking it day by day and, like yourself, I'm using the added energy to get some stuff done.

 

[hmnr asg]

@leokitten just had to mention how very, extremely close (one to one really) your description of your sleep as ME symptom is — how copy-paste it is to mine, and how similar our reaction to Abilify was (for sleep). Your description of it fixing your sleep was exactly my same experience…

yup! same for me! For the two months that it worked, I was sleeping like a normal person, waking up at normal hours and feeling refreshed when i woke up. I had forgotten how that feels like. I really feel like Abilify got to the root of the problem when it was working. This is the only real thread there is to an eventual solution. I just hope they follow this thread.

 

[leokitten]

Abilify, at least in an ME subset, definitely targets some very important ME pathology. For me though even though it has worked remarkably on almost all symptoms I can say it has zero effect on one major one.

At night I occasionally get strong gut and abdominal irritation, night sweats, itching, and the abdominal irritation causing I kid you not irritation shooting up my vagus nerve or spinal cord to my brain causing me to wake up almost violently and be suddenly wide awake and unable to sleep like it scrambled my brain. When it happens at night my next day is totally ruined it feels like it causes me poisoning brain damage and exhaustion I feel disgusting.

I’m guessing these symptoms are mast cell activation related as it’s the only thing that seems to line up. Abilify doesn’t seem to help at all with this and on these nights my sleep would be bad again.

I’m also guessing that Abilify doesn’t help an ME subset because their particular ME symptomatology is driven more by symptoms like this that aren’t helped. If I had this mast cell symptom cluster more frequently like I used to I could see myself finding Abilify not having such a positive effect.

 

[jaybee00]

Don’t know if overall sleep was better for me, but Abilify got me up and out of bed early in the morning…like showered and out the door by like 7 am. Would get a bunch of stuff done before 9am, which was nice. That doesn’t happen any more.

 

[andyguitar]

I’m guessing these symptoms are mast cell activation related as it’s the only thing that seems to line up. Abilify doesn’t seem to help at all with this and on these nights my sleep would be bad again.

Would you see this as an indication that you have 2 different illnesses?

 

[Martin aka paused||M.E.]

due to reduction of heart rate variability in ME, but is this really proven and settled? I thought not

That sounds rather bad than good.

Interesting you report better sleep. I had the worst sleep ever on Abilify and now the same with Cariprazine.

@gm286 did you try Amisulpride?

 

[Jessie 107]

I must be in the minority, I have been on Abilify for a year now, and it is still working at 2mg.
I am sleeping well, feeling ok in the morning and still able to leave my bed ( I'm bedbound)
And rest downstairs every day, I can also lay down outside and have a occasional bath.

 

[gm286]

Yes @Martin but the effect was not a good one for me. I wanted to try Wellbutrin as an adjunct to my lexapro but it was discontinued in France it seems. I ordered some but at the rate that it is taking for the medicine to arrive (ordered four weeks ago) the shipment is not too reliable.

 

[leokitten]

Would you see this as an indication that you have 2 different illnesses?

I don’t think so because it’s just way too coincidental to get these two, supposedly independent (I’m assuming you mean that), illnesses at the same time? (When I got ME) It’s so hard to tell what is part of core ME pathology or a comorbidity triggered by core ME. But what I do know is Abilify didn’t effect my occasional night suspected mast cell related symptoms but it affects pretty much every other symptom.

 

[leokitten]

That sounds rather bad than good.

Yes a reduction in HRV is considered bad and it supposedly found in many with ME. But the casual connection to ME sleep issues is this settled science? I thought not I thought it was just a hypothesized cause.

 

[leokitten]

I want to report that the last two nights and following two days my sleep again went back to pre-ME great and during the day I’ve suddenly felt as well as I’ve ever felt during Abilify. I’ve only been off the med for a couple days so it’s still pretty much near the plasma concentration my body was used to.

So I don’t know now if I should stop, I just had this increased downturn in sleep quality and then increase in ME symptoms the past few weeks so thought it was going to be the temp end of my current Abilify journey but then suddenly now I’m as good as ever?!?

Like others have reported here, I’ve had these sudden positive increases in efficacy after thinking I was possibly becoming tolerant in the last months, so all I can say is I don’t know what is going on with how Abilify is interacting with my ME pathology and body.

I also thought that maybe being on the med and having as many good days as possible will push my body into the direction of remission or long-term improvement? Because on the good days my body feels pretty good like it’s not adding to any cumulative ME damage. I know just speculation but in the back of my mind a lot…

 

[WantedAlive]

So I don’t know now if I should stop, I just had this increased downturn in sleep quality and then increase in ME symptoms the past few weeks so thought it was going to be the temp end of my current Abilify journey but then suddenly now I’m as good as ever?!?

This is much the same experience I have but on much smaller dosing compared to most. In fact, I enjoy the best effect from Abilify just coming off steady state than I do dosing up to, or sustaining steady state. There's some weird saturation effect here that I don't understand. I'm now working with pulsing the dose, lower dose one day, higher the next. I may even dose every other day (with a higher dose) to compare. I'd love to be continually coming off the drug to enjoy the best of it, but obviously that's not possible!

When I exceed a certain daily dose threshold I start to get much worse. I then skip a day, feel much better than while I'm dosing, then resume the following day at a fractionally lower dose and sustain that steady state. If it's kicked in again for you @leokitten maybe you could resume at a slightly lower dose, or skip one in three days.

In my first trial I found the same effect, as I came off it it kicked in again, and using a steady state calculation chart I determined my daily dose threshold was around 0.2mg. I must be a very poor metaboliser of Abilify. Thinking that metabolising enzyme CYP2D6 might be inhibited by CBD oil and Doxepin, I discontinued them both, and started a new trial. Nothing changed at all, I still cannot tolerate a daily dose of 0.25mg or higher, it actually makes me worse than without Abilify, whereas it helps at 0.19 - 0.20mg. I'm now having 0.19mg one day, 0.25mg the next, and that seems to work better than daily 0.22mg. Go figure!

 

[JES]

Yep, there are definitely curious things about the dynamics of these drugs. I haven't trialed Abilify yet due to not getting a prescription, but I have trialed several other psychiatric drugs.

I have yet to find a psychiatric or any other drug for that matter that would keep working at dosage X forever. What I notice is that I actually feel best during transition phases compared to steady state. What often happens is the following. At first I notice an improvement in symptoms, typically already after 12 hours or so. From the 12 hour mark, the uptick in functioning lasts anywhere from around a day to 3-4 days, nowadays rarely much over a day, but it's still pretty remarkable.

Then after noticing the drug has stopped working, obviously I decide to reduce the dosage at some point. What happens next is the exact mirror of when I started the drug, i.e., I start noticing improvement in functioning and sleep. This then goes on for as long as I can manage to reduce the dosage before I reach a new steady-state, at which point baseline symptoms return.

Obviously, this doesn't offer much insight into what is the best or any scheme of taking these drugs long-term that would actually work. I guess there's also a possibility that the dosage that @leokitten took was simply too high (even though I reckon you were already on lower end of the spectrum for Abilify ME/CFS doses). Perhaps if you were very close to or slightly over the critical threshold, you managed to get back to the sweet spot after taking a break.

 

[leokitten]

@WantedAlive Yes it’s very strange and confusing! But this drug at the very low dose range we are taking is really doing so much.

And for those in the ME community who might be reading this and without evidence or reason think this drug is simply producing a placebo effect and we are just experiencing illness fluctuations let me be very clear with my experience…

Before low dose Abilify I never experienced rapid disease fluctuations in many years, only extremely slow disease severity changes (mostly worsening) occurring over many months to over year or two. I was bedridden 23 hours a day for almost 6 months before starting Abilify. For the entire 7 months I’ve been on it, there are quite a few symptoms that it made completely disappear which for every day for 8 years of ME before Abilify were constantly there non-stop. Like off the top of my head for example tinnitus and severe eye orbital pain after overexertion, I had these all the time for 8 years now since 7 months totally gone!

This is not a placebo effect and any ME scientist or clinician who doesn’t take this seriously and constructively is ignoring what, to the best of my knowledge, appears to be anecdotally one of the most efficacious drug treatments ever for ME and something that needs to be spurning more research. I know Abilify it’s not the answer, but it is the first step towards figuring out some answers.

At least for me it’s the only thing other than the temporary almost remission I had on keto that has had a huge significant effect on this illness, all else has failed to do anything.

 

[leokitten]

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

To me we don’t know if the reason Abilify stops working in many or most pwME after 3-4 months is because of Abilify’s known side effects on cellular metabolism and glycolysis, particularly if what is driving ME is cellular metabolic dysfunction.

It could be that after 3-4 months this eventually builds up and rears it’s ugly head within dopamine and serotonin system neurons, glial cells and mitochondria, and basically counteracts the positive stabilizing/modulating effects the drug has on these systems.

I wish we could get brilaroxazine into a small trial for ME or on compassionate use grounds, because this is the big game changer with this drug. It does not have metabolic side effects unlike all other antipsychotics, in fact it has shown so far to have mildly positive metabolic effects. So basically it works as strongly as Abilify with no metabolic side effects. Sign me up!

On the brilaroxazine front, good news from Reviva Pharmaceuticals, they raised $34.5 million from investors and will start phase III trial of brilaroxazine for schizophrenia in Q4 this year.

So if things continue to be successful the drug will be FDA approved and available in the US in 2025. They are also in earlier stages trialing for depression, pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and possibly other indications. I think they will start phase II trials for PAH and IPF in the near future.

https://ir.revivapharma.com/news-re...als-holdings-inc-reports-second-quarter-2021/

For those who didn’t see the posts on brilaroxazine, it’s also known as oxaripiprazole as it has one important atom change in the small molecule, and this change gives it an even better binding profile than aripiprazole and really importantly it has shown so far in humans to have zero metabolic side effects in phase I and II trials. This would be a first for an antipsychotic drug.

It’s binding profile also seems to follow a similar functional selectivity and partial agonist activity as Abilify at low doses compared to higher doses. Trialing this drug for ME at least to me who help answer the question if the metabolic side effects of Abilify are the cause of tolerance/efficacy loss for some in ME.

 

[Martin aka paused||M.E.]

This is not a placebo effect and any ME scientist or clinician who doesn’t take this seriously and constructively is ignoring what, to the best of my knowledge, appears to be anecdotally one of the most efficacious drug treatments ever for ME and something that needs to be spurning more research.

Finally, thank you. That's what I was talking about one year ago when no one believed me.

It's tragic for me that it doesn't work anymore but I very much hope that they look closer into the mechanism of action. They failed to do so with Ativan which is driving me nuts!

It might be a bandaid that only works for a certain amount of time. But it has the potential to tell us more about the pathomechanism involved in PEM bc at 4 mg it did not have ANY PEM AT ALL, not from exercising nor working 12 hrs per day/ 7 days a week!

I'm so disappointed with what happens in research. Watching the IACFS/ME was such a disillusionment.

Especially Dr. Bonilla who responded to my question about what one could do if Abilify stops working that he WOULD NOT BE AWARE OF ANY CASE though I know that he is. He just lied to me and hundreds of others and his colleagues and as a consequence stopping them to take a closer look.

End of story.