Abilify- Stanford Clinic Patients

[mitoMAN]

@Martin aka paused||M.E. did you drop Celecoxib before Abilify pooped out? I think you are taking both?

"Celecoxib may increase the blood levels of ARIPiprazole."

 

[Martin aka paused||M.E.]

@Martin aka paused||M.E. did you drop Celecoxib before Abilify pooped out? I think you are taking both?

"Celecoxib may increase the blood levels of ARIPiprazole."

I took it until last week

 

[bensmith]

Just saw another story on facebook of bad poop out. Very severe young lady (amelia)

3 to 4 months

 

[leokitten]

Just saw another story on facebook of bad poop out. Very severe young lady (amelia)

3 to 4 months

So very interesting that it’s approximately the same amount of time for almost everyone who experiences Abilify poop out.

I REALLY REALLY hope the anecdotal reports of cycling with 4+ month breaks will work for everyone.

 

[hmnr asg]

I REALLY REALLY hope the anecdotal reports of cycling with 4+ month breaks will work for everyone.

The weird thing that is happening to me is that once i go off abilify i end up with severe restless leg syndrome (RLS), which i didnt have before i started abilify.

I believe this is caused by cymbalta that im taking. Before cymbalta, every antidepressant would give me RLS but when I started cymbalta i didnt have it. Once i started abilify and went off of it i started a very severe RLS which went away when i resumed abilify.

I'm taking cymbalta for trigeminal neuralgia pain, so its not that easy to go off of it either.

So seems I cant even take a holiday from abilify.

 

[leokitten]

RLS is thought to be caused by dopamine system dysfunction in the basal ganglia. Cymbalta could play a role because drugs that raise serotonin can have a dampening effect on dopamine in certain areas of the brain. Antidepressants can trigger RLS for this reason. Are you doing a higher dosage regimen of Cymbalta twice a day?

RLS can also be caused by iron/ferritin deficiency or other vitamin or mineral deficiencies that then cause dopamine dysfunction. Definitely worth looking into this (see online resources for the various deficiencies like iron, ferritin, folate, magnesium, etc)

Though you didn’t have RLS while on Cymbalta before starting Abilify yet after a few months on Abilify when you came off it it started. Seems like Abilify made some dopamine or serotonin system network and neurotransmitter changes after taking it over this period of time, which isn’t unexpected but now these systems have changed.

Antipsychotics can trigger RLS but really only at antipsychotic dosages where they shutdown dopamine signalling. The reason Abilify stops the RLS (that it maybe created) is that it’s stabilizing dopamine function, so coming off it RLS comes back.

You could go off of Abilify for an extended break and simply add pramipexole (dopamine agonist) which is an FDA-approved drug for RLS.

 

[hmnr asg]

thank you @leokitten for the response.

Are you doing a higher dosage regimen of Cymbalta twice a day?

I am taking (and have been taking) 40mg once a day in the morning for the last two years.

RLS can also be caused by iron/ferritin deficiency or other vitamin or mineral deficiencies that then cause dopamine dysfunction.

I have a history of RLS which gets worse with antidepressants. I have gone through the gamut of tests. It has been going on for many years now.

You could go off of Abilify for an extended break and simply add pramipexole (dopamine agonist) which is an FDA-approved drug for RLS.

I would, but I worry that taking pramipexole wouldnt be exactly a "break" from abilify since they both affect dopamine systems.

I am thinking of somehow cross tapering from cymbalta to clomipramine or another TCA to address my trigeminal neuralgia.

 

[leokitten]

I’ve been on Abilify for 2 1/2 weeks now and went up to 0.5 mg/day a little while ago. I decided to go to 0.5 mg before reaching 2 weeks on 0.25 mg because I didn’t experience any improvements at the lower dose, and even initially at 0.5 mg I didn’t notice anything.

But recently I’ve started to feel better across all my ME symptoms. It’s not sudden with this drug it kind of just creeps up on you over a few days if you are taking the right dosage for you and your ME symptoms start to improve. Long story short: for me this drug seriously works.

I’ve been bedridden for almost 5 months with only the ability to sit up in bed or get out of bed for 1 hour or so a day before getting strong fatigue and PEM. I could not self care more than every couple weeks and I would almost pass out with dizziness, nausea, cold sweats from being upright in the shower. I would need to immediately lie down horizontal. Even before being bedridden I was mostly housebound (again) since late 2019 - beginning 2020.

I recently started feeling that I could spend more time out of bed and in the living room sitting upright. I can have more conversations and social interactions. I can even walk around my apartment more and take more steps per day. I don’t experience PEM at all from doing this all of a sudden.

All of this was totally impossible just before Abilify. All of you know exactly what I mean because you could easily produce PEM over and over again by doing exertion of specific levels based on your severity. Not just sometimes but for me every single time I would get severe PEM and crash from doing any of this. Now no PEM.

For me this drug is not really stimulating in any way at this dosage. My ME just feels better. I also have no discernible side effects. My ME wired insomnia and sleep disturbances were already bad before Abilify and it hasn’t made it any worse at this dosage.

I was worried this drug would stimulate me and push me to overexert like the ketogenic diet did, but at 0.5 mg it’s not doing that. I think it’s a real plus that Abilify comes as a 1 mg/ml solution since this allows you to find the right dose.

Honestly I’m just really happy and a bit emotional that I’m out of bedridden ME hell at least for a little while (if the drug stops working in a few months).

 

[andyguitar]

I was worried this drug would stimulate me and push me to overexert like the ketogenic diet did, but at 0.5 mg it’s not doing that

Not doing to much, even if you feel you can do more, might be the key to how to get a long lasting improvement from Abilify.

 

[leokitten]

Not doing to much, even if you feel you can do more, might be the key to how to get a long lasting improvement from Abilify.

Yep I’m following that mantra, I’m staying housebound even though I feel I could walk outside some and I’m not doing significantly increased mental exertion.

 

[andyguitar]

Good. Steady as she goes @leokitten remember the tortoise and the hare.

 

[leokitten]

I also forgot to tell people that I didn’t experience any difficult period during the first week or so taking Abilify like others reported feeling temporarily much worse and irritable. I didn’t have any of that and like I wrote above didn’t feel any different at all compared to pre-Abilify for quite a while.

 

[S-VV]

I remember talking to an anesthesiologist that treated crps (one of the "suicide diseases" alongside trigeminal neuralgia) and he emphasized that 5 drugs that improve symptoms by just ten percent usually net a 50% or more clinical improvement when taken together. If so, we may not be so far from a viable ME/CFS symptomatic treatment.
LDN: 10%
Apiprazole: 10%
...
Any ideas?

 

[leokitten]

I’m also taking 4.5 mg LDN and 30 mg etoricoxib (Arcoxia) per day to hopefully synergize with Abilify. I started them at the same time as Abilify.

 

[S-VV]

I’m also taking 4.5 mg LDN and 30 mg etoricoxib (Arcoxia) per day to hopefully synergize with Abilify. I started them at the same time as Abilify.

Nice! I have been thinking for some time that COX-2 inhibition would be a low hanging 10%. For me acetaminophen and ibuprofen + caffeine certainly do the trick

 

[leokitten]

Hopefully soon another new dopamine-serotonin stabilizer Brilaroxazine (also known as Oxaripiprazole) will be out in the market.

https://en.m.wikipedia.org/wiki/Brilaroxazine

It’s almost identical molecular structure to aripiprazole, with only a single carbon change in the quinolinone ring system to oxygen making it a benzoxazinone ring system. The resulting change also makes it closely related to cariprazine.

Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: "A New Option to Address Unmet Needs"

Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder. Cantillon et al. Schizophr Res (2017)

RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia. Rajagopal et al. Behav Brain Res (2017)

Brilaroxazine (RP5063) seems to have fewer potential side effects compared to aripiprazole (which itself already had fewer side effects than other antipsychotics).

Brilaroxazine doesn’t seem to cause any metabolic side effects compared to placebo and other antipsychotics, which is a big improvement compared to even aripiprazole. Patient’s glucose, lipids, and prolactin all actually decreased, and there were no significant changes in weight.

@Janet Dafoe I think Ron was looking for an alternative dopamine-serotonin stabilizer drug with a similar mechanism of action and binding profile to aripiprazole but doesn’t have the negative metabolic side effects, well brilaroxazine seems to be a good candidate.

They’ve already completed phase 1 and phase 2 trials for schizophrenia and are preparing phase 3 (https://revivapharma.com/clinical-trails/). Reviva Pharmaceuticals who is developing brilaroxazine is in Santa Clara, CA so just around the corner from you! https://revivapharma.com/

A good summary document on brilaroxazine from an investment research firm looking at Reviva.

https://s1.q4cdn.com/460208960/files/News/2021/Zacks_SCR_Research_01132021_RVPH_Vandermosten.pdf

You can see the important improvements compared to aripiprazole, eg target receptor binding and affinities, virtually non existent off-target binding, much improved side effect profile (see bar charts summarizing results from phase II trial and comparing to aripiprazole 15 mg).

There’s also a decent summary table comparing all the existing antipsychotics at target receptors.

They are starting phase III trials (for schizophrenia) this year and looks like if everything is successful will be FDA approved in 2025. They are also in earlier trials stages for other indications and looks like it has potential for quite a number of indications.

 

[leokitten]

I’m also taking 4.5 mg LDN and 30 mg etoricoxib (Arcoxia) per day to hopefully synergize with Abilify. I started them at the same time as Abilify.

I forgot, I’m also taking 300 mg/day moclobemide. I started moclobemide monotherapy over two months before starting Abilify and didn’t experience any significant improvements in ME symptoms from it.

It didn’t get me out of bedridden state and severity level. It helped a little with mental energy while in bed and definitely seemed to help feeling more at ease with the horrible situation of being bedridden and possible future becoming more severe, likely due to its antidepressant effect.

RIMA MAOIs like moclobemide work differently than SSRIs/SNRIs and I was hoping continuing to take it with Abilify would have a synergistic effect, even though alone moclobemide didn’t have a significant effect on ME symptoms.

Also important to note, I’d trialed LDN 4.5 mg a few years ago and it did nothing for ME symptoms, and last year I also trialed etoricoxib and didn’t notice a significant improvement in ME symptoms on its own. So I’m just hoping these will also work in synergy with Abilify.

 

[Jessie 107]

Yep I’m following that mantra, I’m staying housebound even though I feel I could walk outside some and I’m not doing significantly increased mental exertion.

So good to hear that you are doing well on Abilify, it's 7months for me now and it's still working.
Yesterday I was able to sit outside for half an hour in my wheelchair, it was amazing to be outside on a beautiful day.
I still pace myself though and I think that is key.
I hope you continue to gain a better quality of life on Abilify.

 

[leokitten]

@hmnr asg found this, I got access to full paper (see attached pdf)

Syk and Src-targeted anti-inflammatory activity of aripiprazole, an atypical antipsychotic. Yoo et al. Biochem Pharmacol (2018)

Aripiprazole (ARP) is a partial agonist of dopamine D2 receptors that is commonly prescribed to treat schizophrenia and bipolar disorder. The anti-inflammatory effect of ARP was recently documented in a few studies, but its molecular mechanisms have not been fully elucidated. In this study, peptidoglycan (PGN)-treated macrophages (RAW264.7 cells), reporter gene assay, an overexpression strategy, immunoprecipitation, and immunoblotting analysis were employed to clarify the anti-inflammatory mechanism of ARP. ARP was found to dose-dependently inhibit production of nitric oxide (NO) and prostaglandin E2 (PGE2) without exhibiting cytotoxicity. In agreement with this result, ARP was found to suppress the mRNA expression levels of inflammatory genes such as cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and tumor necrosis factor (TNF)-α. Luciferase assay and immunoblotting analysis with nuclear fractions showed that activator protein-1 (AP-1) and nuclear factor (NF)-κB are targeted by ARP. Similar to these data, c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 4 (MKK4), MKK7, and transforming growth factor beta-activated kinase 1 (TAK1) for AP-1 activation, and inhibitor of κBα (IκBα), IκBαkinase α/β (IKKα/β), AKT, phosphatidylinositide 3-kinases (PI3K), spleen tyrosine kinase (Syk), and Src for NF-κB activation were revealed to be inhibited by ARP treatment. These results suggest that ARP can suppress inflammatory responses triggered by Gram positive bacteria through suppression of both AP-1 and NF-κB pathways.

 

[leokitten]

Abilify’s potential anti-inflammatory and immunomodulating characteristics...

Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis. Crespo-Facorro et al. medRxiv (2020)

Background Antipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID19-related immunological parameters.

Methods Differential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naïve patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects was performed.

Findings 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher’s Exact Test, two tail; P value=3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the “inflammatory bowel disease (IBD)” (the most significant pathway with a P adj of 0.00021), “Th1 and Th2 cell differentiation” and “B cell receptor signaling pathway”, all three related to the defense against infections.

Interpretation This exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.