Aripiprazole - Abilify

I understand and sympathise with your thoughts on this, @lunarainbows.

And I hope you don't mind me saying it is the very reason why taking too much notice of how individual patients respond to unresearched treatments can cause harm. So little is known about ME, we don't even know whether we all have the same condition, and so many exciting sounding treatments are followed by temporary improvements for individuals, only for them to relapse into an even worse state afterwards.

I would not criticise anyone who shares their experiences, or anyone who decides for themselves on the basis of that personal anecdote to try something too. I understand the desperation that drives us to do that. But please, please, everyone, be careful.
 
I understand @Trish and I’m glad for you saying so. It’s those thoughts as well that makes me worried. Another worry I have is not only whether it would make ME itself worse in the long run, but the side effects on my brain chemistry. My counsellor who knew about Autism warned me that some people wi autism can react very badly to very small doses of psychological drugs. And I already have a few of the more serious side effects that are written on there, which if they got worse, could put me at risk of harm. Like I don’t want to get worse intrusive suicidal thoughts (which I already do have, but do not and will not act on), and if it then changes my brain chemistry, it could be much worse. I already take notrypryline at a low dose and have not noticed any of those issues getting worse, despite this being a warning on the box, but it could interact with that.

The other worry I have is that I wouldn’t be monitored by someone who understands interactions. Like, I take Ivabradine to bring down my heart rate or blood pressure medication but I have regular reviews with doctors who regularly use it, who have seen it in trials, and know how to monitor it and look at side effects. For this, no one knows as it’s so new in ME.

I am also so desperate to get better, especially recently when hospitals are give me such a hard time and I know the reason I’m even in this situation is because of how severe my ME is. If it wasn’t so severe, I would have just been allowed and even able to have surgery anywhere and I wouldn’t be suffering and getting weaker like this. It’s my sensory sensitivities that make it this bad and I’m so angry at myself that it’s like this. Plus the housing situation. So seeing these stories in Pw Very Severe ME is what makes me wonder and think about it. Some of the stories sound amazing, you’re right I think the fact Whitney is well known also makes it more popular, so more people in the groups are talking about it and trying it. But I am also scared of getting worse and the side effects (which I might not know about until it’s too late), and knowing it’s not been studied, and all the things you said too.
 
lunarainbows said:
I remember thinking a while ago that if there’s a drug that gets Whitney better.. that’s the one I would try.
Click to expand...

Just wanted to be clear, this is not just because of Whitney being a famous patient. Well, it probably is to an extent because I wouldn’t have heard about him otherwise as I’m not that active on fb forums. But it’s more because a lot of what he and his parents said regarding his symptoms (sensory sensitivities, difficulty with people, eye contact), is very similar to me, so although his condition is worse than mine, what was described came close to my symptoms. Whereas when I hear of people with different or milder symptoms getting better, I tend not to take as much notice. And I know he’s tried a lot of drugs before that didn’t work or made him worse and he’s been through a lot. So that’s why I was interested - it’s not just that he’s a well known patient, although I know that does have an effect on people including me. I find that when I hear stories I often end up picking up on similarities between me and someone else.
 
Last edited:
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.
Click to expand...
 
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.
Click to expand...
 

Attachments

Jonathan Edwards said:
I suspect that dexamethasone completely covers these targets.
I cannot see any need to look for more vaguely a bit sort of anti-inflammatoryish drugs.
Click to expand...

I think it is likely stronger than placebo, but also I believe it mediates its positive effects via dopamine and serotonine. More like rocket fuel, Abilify is.
 
leokitten said:
To me the paper is interesting not in relation to COVID-19, but to possible (hypothetical) mechanism of action in ME/CFS.
Click to expand...

But we don't have evidence of inflammation in ME/CFS. If Syk kinase was involved I think one would expect some evidence of immune activation like raised CRP and there isn't.

It looks to me as if someone with a financial interest in repurposing aripiprazole because it isn't selling much is trying to dredge up ideas.
 
Jonathan Edwards said:
But we don't have evidence of inflammation in ME/CFS. If Syk kinase was involved I think one would expect some evidence of immune activation like raised CRP and there isn't.

It looks to me as if someone with a financial interest in repurposing aripiprazole because it isn't selling much is trying to dredge up ideas.
Click to expand...

Abilify is not selling much? Ehm, no.
 
Jonathan Edwards said:
But we don't have evidence of inflammation in ME/CFS. If Syk kinase was involved I think one would expect some evidence of immune activation like raised CRP and there isn't.
Click to expand...

I think Syk elevated CRP assumes the inflammation is systemic or at least outside CNS?

I believe that Syk and Src are part of a microglial activation pathway. So maybe the “inflammation” (I know, you don’t like this word in relation to microglial activation) is in CNS and you wouldn’t see elevated peripheral CRP.

We do have some limited evidence of microglial activation in ME/CFS, and hopefully another paper coming soon on it (Stanford James lab) which replicates some of the Nakatomi findings.
 
leokitten said:
The pharma company that discovered aripiprazole already has a new FDA approved drug for the same indications, brexipiprazole (Rexulti). So I have my doubts that the authors of the paper, if related to the company at all, have this as a principal intent.
Click to expand...

On the other hand I find it extraordinarily difficult to understand why anyone without a commercial motivation would bother to test a drug so obliquely relevant to a severe viral response.

Strategies for repurposing drugs are very complex. Companies may not want to queer a pitch for a potential money-making drug for one condition with studies in another condition that might fail or reveal adverse events.
 
leokitten said:
I think Syk elevated CRP assumes the inflammation is systemic or at least outside CNS?
Click to expand...

I said like CRP - there are lots of others that are also missing. If the Nakatomi study is replicated that would be very interesting but it is a very long way from providing a rationale for using a drug that might be a little bit anti-inflammatory when major anti-inflammatories like steroids have proved ineffective.
 
You must log in or register to reply here.
Back
Top Bottom