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Antidepressants, Selective Serotonin Reuptake Inhibitors, SSRIs

SSRIs, including Prozac (fluoxetine), increase the activity of Poison/"Vitamin A" in the nervous system (see other thread on neurotoxicity of Poison/"Vitamin A") via decreasing its breakdown/detoxification.  This would also start to explain the weight gain that happens with these medications (see other threads for the connection between Poison/"Vitamin A" and weight gain).

The title on this next paper is pretty straightforward!

Direct inhibition of retinoic acid catabolism by fluoxetine.

Experiments revealed dose-dependent inhibition of synaptosomal RA degradation by fluoxetine along with dose-dependent increases in RA levels in cell cultures. 

I have a theory that the dependence created by SSRIs is directly related to how they inhibit or even "break" the proper Poison/"Vitamin A" detoxification pathways.

Enhancement of Local Retionic Acid Signaling: A Pivotal Mechanism in Fluoxetine's Pleiotropic Actions

Major depression (MDD) is one of the leading global causes of all non-fatal burden of disease. Involving monoaminergic imbalances, but also hormonal, structural and inflammatory alterations, the underlying pathogenesis remains incompletely understood. The antidepressant drug fluoxetine, which may be considered the “prototype” of all selective serotonin reuptake inhibitors (SSRI), appears to affect all of these processes. Interestingly, this is also the case for retinoic acid (RA), the highly potent active metabolite of vitamin A. In this review, we discuss RA signaling as a central mechanism of action – and missing link – for the multiple, pleiotropic effects of fluoxetine in the CNS, suggesting that direct inhibition of CYP-450-mediated RA catabolism by fluoxetine results in increased local concentration, and enhanced paracrine RA signaling in the CNS.

And here we have the authors suggesting that the CENTRAL MECHANISM OF ACTION (aka "how SSRIs work") is directly related to how they impact the liver's cytochrome abilities to breakdown Poison/"Vitamin A".  In concert with what I stated above, if this is the mechanism by how they supposedly "work", then that is also the likely culprit of how they cause dependence and later problems!  Is this another example of the Duration Paradox?

ljennings13 and Robert Brauer have reacted to this post.
ljennings13Robert Brauer
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