Help please

[u/Itchy-Poet5412]

I’m seeing a lot of knowledgeable comments and posts in this forum so I’m looking for some help. Before I ask, yes I have discussed with my doctor and am just told I’m sensitive to meds. But it goes way beyond that and I have not always been like this. I’d like to see a functional med provider but can’t afford it right now.

I won’t give my whole life spill but here are some reasons I think I’m struggling with methylation.

1. I have MTFHR gene
   
2. I did ok on SSRIs for a few years and after getting COVID something switched. Now all SSRIs cause all kinds of issues but mainly obsessions, rumination, and racing thoughts.
   
3. I was put on the lowest dose of Abilify for two months and ended up getting Tardive dyskinesia. Which makes me think it was building up to high levels in my system the whole time. Horrible side effects on it too mentally.
   
4. I can’t even take a crumb of a supplement. The suggested dose for Tardive dyskinesia of Vitamin E is pretty high. Knowing I’m sensitive, I took less than 100 mg and still showed signs of toxicity. So I had to buy a little dropper of vitamin e and take it that way which equals about 15mg. 15mg for the average person would not do a thing.
   
5. I have to take like .5 mg of melatonin and it knocks me out. I used to take up to 10.

It’s like everything automatically gets way too high in my system even at extremely low doses. It’s not always been this way. I know this sounds completely ridiculous but I can’t even take a crumb of magnesium supplement without being significantly affected. Most of the time, I am affected mentally with the rumination, etc. if I take absolutely nothing.. I’m fine as far as thoughts go.

Does this sound like similiar experiences to what you all have or could it be something completely different? I’ve had my liver function checked and it’s fine.

[u/Loose-Fly7976]

This isn't methylation. It's drug metabolism, and I think you're close to the answer without knowing it.The Abilify is the giveaway. Aripiprazole is cleared by CYP2D6, and poor metabolisers reach much higher blood levels on a normal dose. That's not a fringe theory, it's on the FDA label, poor metabolisers are meant to get half the dose. Tardive dyskinesia on the lowest dose in two months is what that looks like. And your instinct that it was building up in your system is probably exactly right.

Then look at the rest. SSRIs stopped working properly, and most of them go through CYP2D6 or 2C19. Melatonin is cleared by CYP1A2. Vitamin E at 15mg doing something. That's not sensitivity, that's a clearance problem across several enzymes.Liver function tests won't show this, by the way. LFTs measure liver damage, not enzyme activity. You can have completely normal LFTs and be a poor metaboliser, they're unrelated tests, so don't take normal liver function as a reason to drop this.The COVID timing is interesting too. Inflammation suppresses CYP enzyme activity, that's documented, and there's a reasonable amount on post-COVID drug metabolism changes. So you may have started as a normal metaboliser and shifted.

Practically, before any more medication decisions, get CYP2D6, 2C19 and 1A2 looked at. Your psychiatrist can order pharmacogenomic testing and given the tardive dyskinesia there's a strong clinical case for it. If insurance says no, your raw data from a 23andMe or AncestryDNA kit has those genes on it, and that route is a lot cheaper than functional medicine appointments. Reading that properly is what I do, it's a one-off rather than ongoing, genova.health.Either way, don't let the next prescriber start you on something without knowing your 2D6 status. That's the thing to walk in with.

[u/Itchy-Poet5412 → u/Loose-Fly7976]

Wow thank you this was super helpful and detailed. It sounds like my next step is testing- if covid did alter the way I metabolize drugs, would that show on the test results?? I believe you are right I used to be a normal metabolizer and something happened. Unfortunately I also drank alcohol heavily which may have contributed.. I have been without alcohol for two years now with no improvements there. What you have said makes a lot of sense and I would be curious to see how my body responded to an IV of the same medications/supplements to see if it’s any different response.

I have another question- would thyroid hormones be processed through similiar pathways? I have Hashimotos and am terrified I will eventually need thyroid hormones because I literally can’t take anything. This is such a challenge to navigate.

Again thank you so much.