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.

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).

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: )