Nearly all SSRIs undergo hepatic oxidative metabolism before their elimination from the body; therefore, genetic differences in oxidative metabolism can significantly impact the levels of active drug circulating in a patient. CYP2D6 is a member of the cytochrome P450 family of enzymes involved in the oxidative metabolism of drugs. The cytochrome P450 enzymes are involved and if inhibited during inflammation/infection or via other reasons like mag deficiency: levels will be higher: Hepatic expression levels of these enzymes are known to cause interindividual variability. Some SSRIs, such as paroxetine (Paxil), fluoxetine (Prozac), and citalopram (Celexa), as well as statins, are known to inhibit CYP2D6 activity and may make EMs resemble IMs or PMs. Finally, since most SSRIs are also substrates of CYP2D6; SSRIs that both inhibit and are metabolized by CYP2D6 can inhibit their own metabolism and produce higher than expected plasma concentrations.
https://web.archive.org/web/20160302190615/https://emedicine.medscape.com/article/1879354-overview
The CYP2D6 enzyme activity for example ranges considerably within a population and includes ultrarapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs) so checking that would be important for drugs that use CYP2D6.
https://www.snpedia.com/index.php/CYP2D6 And the drug itself in some cases such as with certain SSRIs might also inhibit the enzyme as well. One study found that paroxetine and fluoxetine both inhibited the enzyme cytochrome P450 2D6 (CYP2D6), required for the conversion of tamoxifen to its more active metabolites, resulting in lower levels of these metabolites and, potentially, a reduction in the drug’s anticancer effects so this all requires further investigation and mention to patients and doctors to be more on the lookout rather than the drug itself is bad.
https://pubmed.ncbi.nlm.nih.gov/20141708/ https://pubmed.ncbi.nlm.nih.gov/33498694/
Antidepressants lowered NLRP3, IL-1b and IL-18 so they are anti inflammatory as well and I've had good experience.
The innate immune response releasing pro inflammatory cytokines, such as IL-6, may also have the ability to suppress xenobiotic-metabolizing CYP450 enzymes as well.
https://www.xenotech.com/access-adm...-toll-like-receptor-9-agonist-in-hepatocytes/ Expression of CYP450 enzymes is downregulated in the hepatic tissue during the host response to inflammation or infection
https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.2008.302 Liver disease as well
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1016/j.clpt.2006.05.006 Now that explains why so many are affected with taking medicine that requires metabolism with these enzymes.
On top of that, over 600 enzyme systems require Magnesium as a cofactor to function optimally, including the cytochrome P450 enzymes, and magnesium deficiency is widespread. Aluminum, Mercury, Copper, Polysorbate 80, and others all further may possibly be able to impact the enzymes based on the published research but would benefit from more study.
Also Patients who are overmethylated have an adverse reaction to serotonin-enhancing substances such as Prozac, Paxil, Zoloft, St. John’s Wort, and SAMe. This has been mentioned by Dr William Walsh and others like Dr Mensa
https://www.mensahmedical.com/common-symptoms-of-overmethylation/
SSRI-induced akathisia, suicide and homicide cases were related to cytochrome P450 metabolizer status. Many instances of suicide, violence and shootings are related to these type of medications. Antidepressants have been reported as causing suicide and homicide and frequently producing akathisia, a state of severe restlessness associated with thoughts of death and violence. That antidepressants cause some people to commit suicide has been known since the advent of the tricyclic antidepressants in the late 1950s.
https://www.sciencedirect.com/science/article/pii/S1752928X16300051
