Anxiety / panic - but can’t tolerate SSRIs - COMT MAO MTHFR and various orhers

Is there known information on inability to tolerate SSRIs? I had severe increased anxiety and tried to push through but it got to a point I no longer wanted to live by the 3 week mark. Dr has said they’re elevating me too much and I need to go off them. I’m now seeking a functional Dr to treat me wholistically given this medicine isn’t an option.

I have COMT variants suggesting reduced pain tolerance and lower COMT activity
Numerous ++ MAO variants
MTHFR Hetero c677t

And I just wonder if my serotonin and dopamine levels are affected in these traits and if this is something others identify with?

Of course a functional practitioner will provide a wholistic understanding that isn’t only related to my genotypes but it’s an area of interest for me


I have similar issues with not being able to tolerate SSRI’s. I have had trouble tolerating all anti depressant/anti anxiety medications that I’ve tried. They either make me more depressed or more anxious. I’ve tried nearly all of them too. After about 2 weeks to a month I can hardly stand it. I’m not entirely certain which genes cause the issue though. That’s something I would love to do, is see a functional practitioner.

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Yes. I went to a new doctor at a group practice and he ordered DNA tests from Genesite. It broke down all the different psych conditions with all the prescribed medications, and splits them into Green, Yellow, and Red groupings. (because doctors have so much time to study lab results :wink: ). I thought it was genius - no more trial and error.

So for me, at least I know I’m “yellow” for anxiety meds (hate them, but I’d be curled in a ball of fear the last 20 years w/o…). The first one I was put on was a Red category. Felt like I was falling over or being electrocuted.

I have a TON of methylation cycle variances (referring to Yazko’s huge diagram) and as my health cascaded further and further, the anxiety went through the roof. I’m still trying to understand her “genetic bypass” supplementation protocol - customized for my 23&me data, I’m just too confused anymore. She says “First, get GABA under control.” That’s what’s contributing to so much anxiety for me.

Functional doctor (and their $$$ supplements, but it makes sense). Or a naturapath N.D. I have a immunologist who is very functional yet is head researcher and does a lot with infusions. The goal is to catch it before we get that bad!

Good luck.

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Check your CYP snp’s. If you have snps then the SSRI WILL build up in your system. For example, if you have the CYP2d6 snp, then Prozac is both acts as a substrate and an inducer of the enzyme system. There are 5 snps (cyp1a2, cyp2c9,cyp2c19,cyp2d6,cyo3a4) that are the most researched. CYP Enzyme System If you know your CYP status you can look up how various drugs might affect you in a chart included in the above document. There is a test that your Doctor can order which can guide in the dosage and type of SSRI that might be best for you depending on your CYP status. SSRI and Genetic Tests Mayo I’m unsure why this isn’t a mandatory test for SSRI patients, perhaps too much of a bother or because of the cost of the test? BTW, everyone should know there CYP status, why play roulette with your body and pharmaceuticals?

Psychotropic DNA Test
This looks like an excellent test, perhaps better than others that test only one med at a time. Great resource!!!

It really is. I was on Medicaid at the time and they paid for it!

I’m no doctor but when it comes to my health and meds and illness, I geek out.

I ramble too much (symptom) so feel free to skip it all and go to the links below. They are important for the original poster.

I have had to become my own doctor and advocate. Because I was SO tangential, psych wanted to try bipolar meds. Heck no!!! Life finally defeated my spirit so I agreed to try other meds in addition to what I was on, against my own wisdom. Sure, I’ll try, but only after I researched all the meds in the results. I was SO powerless, it gave me a tiny sense of agency again. I’d point to green meds and doc would know the technical stuff, like post-synaptic or pre-synaptic mode, which are generally excitatory, etc.

It lays the ground for a conversation, basically. Psych only knew 1/18th of the whole picture.

I finally tried adding Buspar after some ‘huge research was published’ and it did nothing but prevent me from eating grapefruit. :frowning: Immunologist knew all along that the cognitive symptoms were from a systemic immune source (hyper IgM that looks like multiple myeloma - off to the blood oncologist…).

When a test came back high and long-term for m.pneumonea (walking pneumonia) and a CT with calcified lymph nodes, I started taking an anti-biotic of sorts for mycoplasma. For leprosy, specifically! But this is long term - years to life.

MASSIVE side effects with the Buspar.

I just quit the Buspar on my own - lungs are more important. So while the Genesite test has 2-4 liver gene/enzyme tests, it doesn’t have all of them. It’s on us as patients to utilize our data and web resources “before it’s too late.” I learned the rest of the liver gene variants from that Genesite missed, and the antibiotic was competing for the enzyme. Not fun.

Also, their “MTHFR” test is just that. So Psych gave me a couple months of high dose 5-methylfolate (more research in psych re: depression - so just throw massive amounts of one vitamin at it!) He was stumped when I came back 2 months later unchanged. Turns out I couldn’t even process 5-MTHF at that point. I had to add adenocobalamin and/or hydroxycobalamin for starters. Even methylcobalamin was stripped of whatever makes it work in the downstream process.

I presented this monster microbiology-genetic-nutrient diagram to both doctors and they were blown away. My immunologist is working with it because Serine is in a compromised cycle for me, and I have A1A-Def syndrome (aka rare lung disease) expressing yet I’m merely a carrier. Serine is the root of it the innate immune system and low C1, the key cytokenes behind A1A-def. So he’s writing research papers now (yay!).

I try to share it w/ everyone who mentions COMT or MTHFR because it opens up a whole new conversation with doctors. The good ones will get curious and start digging with you.

Another version that pulls in heavy metals and specific nutrients:

And you can upload your 23&me data to get a general idea of most of the genes identified:

Click the huge “Start Here” button to start uploading and see if/where your methylation cycle could use support.

This is new stuff, and one Ph.D.'s take on it. It turns out Shoemaker in the book Mold Warriors is wrong about how to collect C4a - based on experience. So the initial works that are always shot down by the Ivory Towers of Academia and Politics aren’t 100%, but they’re so much closer than “all in the mind.”

It’s the most thorough view I’ve found. So when the psychiatrist started saying my sleeping all the time and fatigue were depression, I whipped out the 2 diagrams above w/ my variants circled, which resulted in problems with SSRI, Dopamine (there are 2 MOA* markers, one flows down to Parkinson’s, the other ADHD etc), GABA (root of anxiety in a doctor’s view). Then I pointed over to the Kreb’s Cycle and said “I took Botany during my undergrad, this is energy at the cellular level and for me, it’s broken.”

Ding! I finally earned my credibility card with him.

Hope they help, if not already posted here.

(I know livewello doesn’t have a thorough methylation cascade variant report).

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Thank you so much for your reply, it solidifies for me that the onus is on us as you say. Your enthusiasm and determination are giving me hope in my research. At times, I so want to hand it all over to a geneticist but then realize the futility. It’s personalized to each individual and until better software is developed to analyze genetics it may take hundreds of hours to sort it all out, not something a geneticist would be able to realistically do. I appreciate also that you acknowledged the holes in various snp collections and to keep searching. I hope we can keep this conversation alive as we continue to plunge through the data. (Would give right arm to see the diagram you devised, :slight_smile: )

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Hi @pagekurtz,

I have not forgotten this. Had a reminder set, in fact.
I’ve been contemplating however.
If I had the $ and knew a geneticist, I’d hand it all over in a second!!!
My immunologist ordered the “Primary Immunity” panel at Invitae. He’s always talking to the various testing companies and seems happy with this one (he’s Somebody in the immunology world - Dr. Isaac Melamed).

The test he ordered is this one: “Invitae Primary Immunodeficiency Panel” - 207 genes. I have an appt June 4 or 5, hopefully will have more details on what results look like by then.

Here’s my reservation - the information I’m going to share should not be taken as gospel. It makes TONS of sense (after reading 50 times or so…), and this Dr. Amy Yazko provides online ebooks, presentations, and a forum for her “Methylation Cycle.” Her method is to use your uploaded data (or pay for her genetic test), identify genes such as COMT and MTHFR and other critical ones that cause a slow cascade to DNA and nerve degeneration and the express the dark side of epigenetics. (versus maybe the DNA stitching back up and de-expressing disease) You put in your data, you get out her protocol for nutrients/vitamins that offer “backdoors” to the broken cycles. That’s it in a nutshell.

Mine has 30+ DIFFERENT supplements, and 5 “nucleotides” products, which are about $100 each, for 30 days. This is a lifetime thing.

THAT SAID - I gave it all to my immunologist and he was curious because SERINE is in her map. It’s one of the cycles broken for me, and it’s behind low C1 and a ‘rare’ lung disease called Alpha-1 Antitrypsin Deficiency. I’m ONLY a carrier. However, things have degenerated so badly that the disease is expressing. I got infusions while on Medicaid, but on Medicare I can’t afford $500/week.

Also, his passion project is “Neuro-Immune” - and somehow this is related. (he’s writing research on it, so some day folks will have an answer…) He’s identified a cluster of irregularities that seem to define this “Neuro-Immune” and is looking for the root cause. The supplementation is a “band-aid” as is the 6 anti-infection prescriptions I take weekly and daily.

One is anti-bodies to … erm … the test is called " Anti-68 kD (hsp-70) Antibodies, Western Blot". Generally “diagnosed” as inner ear hearing loss - he’s linked it to cognitive issues among his patients. It’s more than that. So that’s how he thinks. Out of the box. He doesn’t take “oh, it’s just Meniere’s disease, so sorry.” He links things up. This is important.

Another thing he’s linked is Antiphosphatidylserine - there’s SERINE again. But this is involved in blood cancer, lupus, joint diseases, connective tissue, etc etc etc. Antibodies against “phosphatidylserine”. And I have tons of 'em.

If I followed Dr. Amy Yazko’s Methylation protocol, her #1 supplement and the one often highly encouraged in the related forum, I would be INCREASING my auto-immune problems.

See why I hesitate?

Ok, that said, here’s where you can find info on this methylation map. For the record, I’ve added quite a few ‘backdoor’ supplements from more affordable sources and am treating my GUT!!! Probiotics, fermented foods, cabbage tonic :nauseated_face: , and while my ALCAT test came back with milk products having one below severe immune response, I take collagen peptides and “egg-based colostrum”. I will switch to bovine colostrum (ideally goat if I can find it) because 30-days of egg gut immunobodies was $70. I healed my dog’s gut with it, after vets missed chronic hookworm, tapes, rounds - destroyed his gut. With time he healed. So for me, given my body, the risk is worth the gain. (Gelatin is also a good one for the gut - find a good source).

I take SSRIs and ADHD meds - you’ll see Serotonin and Dopamine are cut off w/ the COMT gene, and others. It just compounds.

Your age upon symptom onset (“psych” manifestation of immune source) is important. If you have that. If you’re over say 26 and never had it before, the immune system could be culprit. But modern medicine is band-aid therapy. Treat the symptoms. My anxiety went through the roof and ADHD uncontained by meds towards the end of my 30’s and into 40’s. Mold also causes brain inflammation in me - just rotting wood, nothing crazy. Or mildew in a shower. And it’s labeled psychosomatic and psych, and down that black hole we go…

So that’s my fine print. I don’t want folks hurting themselves - sadly out of desperation from a failed medical system :frowning:

Here’s the main site:

Click the green “Start Here” and you can create a login to upload your 23&me data. It gives you a ‘customized protocol’ of supplements. Read the “Companion Guide” as well - it’s a meaty document. The info seems sprinkled throughout - but I also have cognitive issues and could well just not be able to make sense of it as I once could.

Example: I found out my struggles with cobalamin (B-12 format), and even methyl-cobalamin taxes my liver (part of lung disease enzyme). I need Hydrox-B12 and Adeno-B12. So there is some good info to be found.

The overview of her Methylation Pathway - my #2 go-to diagram:

Homocysteine overload is the SYMPTOM. This approach looks at it as the problem.
It can’t be broken down, so robs neighboring systems of molecules - breaking the systems in the process. So those systems snatch molecules from THEIR neighbor’s system, on and on. That’s the cascade.

This next diagram is my #1 go-to diagram. I printed it out HUGE, so I had to tape 2 sheets together to = 1 page. Then stapled the 5 double-pages together, and that’s what I have in my back pocket when I see a new doctor. I ask them genuinely for help at making sense of it (with my genes highlighted - half). It at least has them reconsider what they’ve already labeled me with before they even open the door - as they are so habituated to doing.

Maybe I have just had bad luck. My experience is doctors ignore the very REAL evidence on their own exam table because it’s not written up in some peer reviewed journal somewhere - so must not exist. (oops, was that sarcastic? my bad…)

The forum:

Sorry for the length. I’ve thought long and hard, but we need any information we can get. And getting into an adept immunologist is hard, much less one that leads global research. I’m never moving!

And for the record, he’s looking at IVIG type therapy to fix the immune system that got out of whack in the first place, causing this whole mess to express. Clinical trials, he just needs to make the case as the criteria is tightly controlled.

Just to show how this could well all just be symptoms of a taxed immune system due to “food-stuff” that’s manufactured, not grown; sugar; anti-biotics; stress; environmental toxins; incorrectly prepared food (ex: all grains, legumes/beans/peanuts have enzyme inhibitors and we eat them ground with wild abandon).

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Here are some other resources that I’ve found helpful in so-called “self-hacking”.

If able, I definitely recommend this test:

For me, it’s “low hanging fruit” - not the magic cure that SIBO patients experience.

Yet with tons of supplements and prescriptions, I’ve calmed down noticeably. I still get super wound and other cognitive problems and my body can’t clear an infection to save it’s life, but I’ve gotten feedback from a few people that I sound better.

I couldn’t string 2 sentences together a year ago. Finally getting out of moldy basements was KEY for me. Reducing small but known immune triggers also adds up over time by reducing the overall load. The innate immune system can be slightly more effective. Things compound (just as they cascade) - and both cases take a long time.

I purchased a diet based on your DNA:

You can upload your genome, or pay for their gene test. And you pay for the diet their algorithm spits out.

If you read the blog, the guy does his research. And the topics he brings up make sense. The problem is - it’s based on the modern medical model of chasing symptoms.

Verdict: you’ll get a diet that may work, may do nothing, or possibly make you worse.

For me, they determined a high carb, low fat, no meat diet was what my genes indicated. However it went 95% counter to my ALCAT food test results: actual measurements of how my immune system reacts to various foods and additives.

This was a let-down for me - but I’m further down the path of illness than hopefully anyone reading this. It makes a huge difference for some people.

Personally, I’m going with my immune response, not the research.

An anecdote:

High cholesterol is not a problem! It’s just an innocent bystander.

Arterial plaque and heart disease is caused by INFLAMMATION - the immune system. The few studies that actually looked at the content of arterial plauqe (surprisingly NOT MANY! it’s like they blindly followed a coincidence). If it hasn’t been destroyed, the one or two studies found the clog in clogged arteries contained predominately polyunsaturated fats and calcified lymph/WBCs. And sugar somehow is a trigger, I forget the exacts.

I worked in tech, and with many folks originally from India. Apparently, Indians frequently have choesterol >300, but they don’t have a problem with heart disease.

(and then they moved to the U.S., heh…)

Two books that, in my opinion, are on the money:

  1. “Nourishing Traditions” by Sally Fallon

  2. “The Fourfold Path of Healing” by Thomas S. Cowan, Sally Fallon, Jaimen McMillan

They are based on “Weston Price” (?) who I guess was denounced as a quack by the medical community. Medicine denounces any person or regimen or knowledge that works without using pharmaceuticals. If a ‘cure’ or ‘higher survival rates’ rely on natural remedies, it won’t be researched and peer-reviewed because companies can’t patent nature. (Although they are starting to!) Since it’s not published research, it can’t possibly be true. It takes to do that research, and is funded by the anticipation of future revenue. Hence, medicine in general provides Rx Band-aids to fix symptoms, and dismisses techniques that cure the root of the problem.

Microscope Myopia? Zooming in so far that it lost sight of the big picture? The body is a dynamic, integrated system that is part of an even larger planetary ecosystem. Slight oversight.


  • TCM - Chinese medicine
  • Ayeurveda
  • Qi Gong / Tai Chi

These are also “quackery” to modern medicine. So why are they still around? And why are the pricey supplement companies like Xymogen and Ortho-Mollecular offering so many ‘new herbal remedies’ for major diseases - that are identical to these traditional remedies?


K, I’m done ranting.
Promise! :blush:

Stay curious, folks!!!