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what is causing adverse reactions to SSRI class of drugs?

hapl808

Senior Member
Messages
2,180
Also, a few years back I used tryptophan for insomnia at 3000mg an hour before sleep and it worked OK. I did notice the next day I felt quite Good mood wise, which I think was the increase in serotonin. I think the tryptophan worked better than 5htp but tryptophan has to be timed better ie a few hrs away from any protein meals, where 5htp supposedly you don't. Tryptophan I don't know why, but is expensive for a supplement especially at 3000mg a day.

That's my experience with serotonin.

I really think neurotransmitters are affected for me, especially since cognitive exertion often crashes me worse than physical exertion (although I can't do much of either one). A 30 min videochat is fun, but will crash me for a week.

I've experimented a bit with tyrosine (initially helpful, but then made it worse), tryptophan (maybe helpful, hard to say), 5HTP (same), and so forth. Since a lot of my symptoms take 1-3 days to manifest (like after a long phone call), so I find it very difficult to figure out what these short half life things are doing, especially when I'm also taking magnesium, allicin, NAC, vitamin C, and so forth.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,129
Location
australia (brisbane)
I really think neurotransmitters are affected for me, especially since cognitive exertion often crashes me worse than physical exertion (although I can't do much of either one). A 30 min videochat is fun, but will crash me for a week.

I've experimented a bit with tyrosine (initially helpful, but then made it worse), tryptophan (maybe helpful, hard to say), 5HTP (same), and so forth. Since a lot of my symptoms take 1-3 days to manifest (like after a long phone call), so I find it very difficult to figure out what these short half life things are doing, especially when I'm also taking magnesium, allicin, NAC, vitamin C, and so forth.

I think they can help some people create more energy, appears more mental type energy than physical energy but we need something in place to help recovery. I'm not sure what that would be, possibly improving quality and quantity of sleep would help as well as have a good dhea to cortisol ratio and for guys a good testosterone to cortisol ratio, both would help contribute to better recovery from activity but not sure either are the holy grail as both of these tactics have been used. Still need to get to the root of the issue I guess. But it's still worth trying while looking for or treating the root issue??
 

hapl808

Senior Member
Messages
2,180
I need to revisit the testosterone ratios. For me, one of the absolute worst things I tried was testosterone - made my muscles feel like they were tearing apart. I wonder if DHEA or pregnenolone might be worthwhile (I've tried DHEA a few times but didn't notice a lot). On tests, my testosterone usually read somewhat high for my age, but DHEA usually a bit low (not a huge deficit, though).
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,129
Location
australia (brisbane)
I just read something last night about Lysine and it's ability to regulate serotonin.

I wonder if it would help with other neurotransmitters as well.

Possibly. I've only looked into lysine as a treatment for herpes viruses. Certain amino acids or just a higher protein diet and lower carbs can increase dopamine levels which could increase mood???

Lysine sounds like it's worth a shot👍
 

datadragon

Senior Member
Messages
404
Location
USA
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.
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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
 
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Messages
4
My husband with ME took 5 mg of escitalopram for 20 days, feeling not particularly bad until the end. He stopped taking it cold turkey because he started feeling too bad to put up with the "expected side effects". It's been 5 weeks now, in which his condition has gotten much worse: very intense mental fog, feeling very weird, all the discomforts concentrated as in a cognitive pem. Now reading this thread I learn that there is such a thing as "serotonin syndrome". He is now taking low doses of prozac (no more than 5mg a day) which is the only thing that helps him to improve the symptoms a bit. I read a while ago also a thread that I can't find now about benzos where @andyguitar made some very interesting comments. If anyone who had a strong reaction to SSRIs could share their experience on how to cope better with these symptoms or if @datadragon could help me (I'm not a science person, so I don't understand very well what you commented, sorry), I would appreciate it very much.
 

Rufous McKinney

Senior Member
Messages
13,465
I"m afraid I could not tolerate the Zoloft ...two days. I had a full page of adverse symptoms I wrote down at the time.

Made me horribly ill, and that included my jaw locked up. Edit: three months to get back to something more normal after two days of Zoloft.
 
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ilivewithcfs

Senior Member
Messages
122
I had bad reactions to stimulating SSRIs (Zoloft, Prozac). Neutral/sedating SSRIs are fine with me.
Fluvoxamine is the best, in my experience. It has strong antiinflammatory effect, which is what we need. 100mg of fluvoxamine took away about 25-30% of my symptoms with no side effects.
In my opinion, stimulating drugs should not be given to most PWME.
 

Rufous McKinney

Senior Member
Messages
13,465
Fluvoxamine is the best,
This doctor I won't see again, recommended I take Lexapro. (after not talking to me at all, and ignoring my daughter's attempts to inform her about ME) (of course, nobody here knows anything about that)

(When she called back to check, told her I won't be taking any of that)

I just read that taking antidepressants when you are not depressed, can injure the brain.

https://www.banyanmentalhealth.com/2022/02/09/effects-of-taking-antidepressants-without-depression/
 

Rufous McKinney

Senior Member
Messages
13,465
Now I am reading that the antidepressant Lexopro- can CAUSE Inflammation.

Also reading that MORE STUDY is necessary on this entire topic. Effects on the immune system ARE NOT CLEAR.

"As a result of our study, we observed that Escitalopram caused a significant increase in TNF-α, IL-6, and GM-CSF levels in mammalian macrophage cells, but did not induce IL-12p40 production. We observed that the p38 and PI3K pathways play a role in inflammation in the presence of Escitalopram."

https://www.sciencedirect.com/science/article/abs/pii/S0278584623000489
 

Blazer95

..and we built castles in the Sky.
Messages
269
Location
Germany
Maybe thats why i feel so good on Citalopram. My IL-6 is so Low it actually Looks supressed.

What Always boggles my mind is how different ME can present and how volatile this disease is. We have atleast 3 reactions on the Same class of drug: Group A with improvements, Group B with worsening, Group C with neither.

These opposite direction comming from the "Same" Disease Just Shows how complex ME really is and that I highly doubt there will ever be one single cure for this. The Key to unlock this illness is understanding every single subgroup and having a remedy ready for each one of them. The medicine will move to this Goal at one Point I am quite Sure, but WHEN will be the Problem.

Oh and by the way: Citalopram inhibits secretion of IL-2 and IL-4 of T Cells this May also Attribute to worsening/improvements.

As for me I am very surprised that citalopram worked for me as its one of the few that ever did, and its actually still working. (From mod-severe and nearly bedbound to moderate wich is housebound in my Definition)


Cheerio
 

andyguitar

Senior Member
Messages
6,647
Location
South east England
My husband with ME took 5 mg of escitalopram for 20 days, feeling not particularly bad until the end. He stopped taking it cold turkey because he started feeling too bad to put up with the "expected side effects". It's been 5 weeks now, in which his condition has gotten much worse: very intense mental fog, feeling very weird, all the discomforts concentrated as in a cognitive pem.
It's a bit strange that it took that long before he started feeling bad -adverse reactions usually start in a couple of days. Could something else be having a bad effect like a change in diet or new supplement?
Now reading this thread I learn that there is such a thing as "serotonin syndrome". He is now taking low doses of prozac (no more than 5mg a day) which is the only thing that helps him to improve the symptoms a bit.
That is a very low dose. Yes Serotonin Syndrome is a pretty nasty thing and there are some drugs and the herb St Johns Wort that can trigger it in those who are taking SSRI's. One point to bear in mind is that Escitalopram and Prozac are similar drugs.
 
Messages
4
It's a bit strange that it took that long before he started feeling bad -adverse reactions usually start in a couple of days. Could something else be having a bad effect like a change in diet or new supplement?

That is a very low dose. Yes Serotonin Syndrome is a pretty nasty thing and there are some drugs and the herb St Johns Wort that can trigger it in those who are taking SSRI's. One point to bear in mind is that Escitalopram and Prozac are similar drugs.

Thanks for your reply, @andyguitar. No, he is not taking any supplements at the moment. He stopped taking Q10 when he started escitalopram treatment. He says the symptoms went from bad to worse, to the point where on the 23rd day he stopped taking it because he could no longer tolerate it.

In my previous post I made a mistake and wrote "prozac" when I meant valium (diazepam). The low doses of this benzodiazepine (between 2.5 to 5 mgs a day) help him quite a lot, but the main problem is that there is a lot of restriction to get it with the GP, and my husband wonders how much benefit he could get if he could take a higher dose, no more than 10 mgs a day. Also, he would like to know if taking high quality omega 3s could help to ease his nervous system at this time and if it doesn't interact with the diazepam.

@datadragon
I would recommend to consider monitoring c-reactive protein levels with your doctor and perhaps trying to not take or intermittently when no longer showing higher inflammation based on my personal experience with taking ssris but your medical practitioner needs to be involved.

Thanks for your explanation. What are the benefits to test this? If I understood correctly, it would be a measurement to consider before taking any drug that can trigger inflammation?

Many thanks.
 
Messages
4
Thanks, @andyguitar ! I’m not sure if it was clear before but the screens aversion and inability to concentrate without feeling ill began before my husband stopped taking it. Since he began to taking it, the effects of escitalopram get worse and worse until they became unbearable after 23 days. Since then initially improved and then stabilised, and then got worse again and then just in the last week he started to feel small improvement. It’s now been 7 weeks since his last dose. Is this kind of a normal timeline? Because he is wondering if he is following a “regular pattern” of withdrawal or SSRI problem with ME.

Thanks for any help.
 
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