Beyond “Psychotropic”: Repurposing Psychiatric Drugs for COVID-19, Alzheimer’s Disease, and Cancer, 2023, Santosh et al

rvallee

rvallee

Senior Member (Voting Rights)
Beyond “Psychotropic”: Repurposing Psychiatric Drugs for COVID-19, Alzheimer’s Disease, and Cancer
https://www.psychiatrist.com/jcp/be...tric-drugs-covid-19-alzheimer-disease-cancer/


Importance: “Psychotropic” drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact.

Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine’s use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer’s disease, cancer, and other conditions.

Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.
 
I've seen some discussions lately of fluvoxamine and its possible relevance to both COVID and Long Covid, especially given their "other" properties. I've long suspected that SSRIs have much more to explain their impacts than some "antidepressant" effect, or even the simple blocking of serotonin receptors.

Unfortunately the obsession over biopsychosocial ideology and its cheap reductionism over simple terms like "depression" and "anxiety" seems to take all the air out of this avenue of research. This is so much more complex than this, and although I don't think that SSRIs are likely to be especially significant, they seem to be a step on the way to understanding where immunity influences behavior and systemic/overall well-being.

This particular caught my eye:
In April 2020, a team of researchers at Washington University School of Medicine (St Louis, Missouri) initiated a randomized controlled trial (RCT) to test fluvoxamine for the treatment of early COVID-19. The motivation for testing fluvoxamine was its strong activation of the sigma-1 receptor (S1R), leading to anti-inflammatory effects.15 Specifically, preclinical research found that S1R activation dampens cellular stress responses by inhibiting activity of the endoplasmic reticulum stress sensor, IRE1. This S1R-IRE1 pathway appears to be an essential mechanism by which organisms regulate inflammation in response to proinflammatory signals such as infection. Preclinical rodent models demonstrated that absence of S1R causes animals to succumb quickly to hyperinflammation induced by inflammatory challenges.16 In contrast, by modulating the S1R-IRE1 pathway, fluvoxamine restricts cytokine expression in models of sepsis, resulting in reduced morbidity and mortality.16 Moreover, fluvoxamine does so without inhibiting classical inflammatory signaling pathways that may be necessary for a successful host immune response to the virus.16 Fluvoxamine is the strongest activator of S1R among the selective serotonin reuptake inhibitors (SSRIs), with a Ki = 36 nM, compared to 120 nM for fluoxetine and 292 nM for citalopram.
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Bit similar here:

SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids
https://www.nature.com/articles/s41398-023-02343-3
When hippocampal slices are exposed acutely to lipopolysaccharide (LPS), a strong pro-inflammatory stimulus, basal synaptic transmission in the CA1 region remains intact, but induction of long-term potentiation (LTP), a form of synaptic plasticity thought to contribute to learning and memory, is completely disrupted.
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SSRIs are lipophilic weak bases and readily access sites within cell membranes and intracellular compartments including direct effects on endoplasmic reticula (ER), Golgi, lysosomes, and the NLRP3 inflammasome, among others [3,4,5,6]. Potential non-serotonin targets include sigma-1 receptors (S1Rs), acid sphingomyelinase (ASM), and cellular enzymes involved in the synthesis of neurosteroids from cholesterol [7,8,9,10,11,12,13]. These various effects can promote intracellular production of brain-derived neurotrophic factor (BDNF) and activation of its primary receptor, tropomyosin receptor kinase B (TrkB receptors), a mechanism thought to contribute to antidepressant effects [14]. Certain SSRIs also appear to interact directly with TrkB receptors [15].
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I wonder how many of these drugs being touted for re-purposing are highly addictive. I wouldn't take a drug I thought was going to wreck my life with an addiction.

Edit : Given that doctors have denied that many common drugs in use throughout the last 70 years are addictive and patients have been told that weaning off is not necessary, I simply wouldn't trust a doctor on this issue.
 
rvallee said:
Beyond “Psychotropic”: Repurposing Psychiatric Drugs for COVID-19, Alzheimer’s Disease, and Cancer
https://www.psychiatrist.com/jcp/be...tric-drugs-covid-19-alzheimer-disease-cancer/


Importance: “Psychotropic” drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact.

Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine’s use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer’s disease, cancer, and other conditions.

Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.
Click to expand...

According to the better studies we've seen fluvoxamine has no effect on Covid or preventing LC:
Unless someone can actually produce good evidence this seems no different to the Ivermectin conspiracy which had to undergo multiple trials showing it didn't work, even though there was no evidence it would work in the first place, all of this money could have been better spent elsewhere to actually help people.
 
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