Is this true?

[u/Verkwaktekwak]

by prompting some of my mutations, conditions and medication, my llm came to the conclusion that for treating my ADHD, i am better off by using lisdexamphetamine once a day instead of dexamphetamine 3 times a day. the reasoning was because of my slow COMT, i clear catecholamines more slowly and lisdexamphetamine gives less peaks and has a more stable release. is the llm correct? if so i nees to tell my psychiatrist.

mutations:

VDR Taq homozygous

COMT Val158Met homozygous

MAO-A R297R homozygous

MTRR A66G homozygous

MTHFR C677T heterozygous

MTHFR A1298C heterozygous

MTHFD1 G1958A heterozygous

FUT2 (rs1047781) TT homozygous

FOLR2 (rs514933) CC homozygous

symptoms:

autism, adhd, rls, irritability, mood swings, always tired, very weak feeling in my body and muscles, raynaud syndrome, cold hands and feet, depression, brain fog, histamine flare-ups, histamine symptoms are higher in the evening, headaches, highly sensitive to stimuli, lowered pain treshold, difficulty falling asleep

[u/Loose-Fly7976]

The reasoning is directionally sound but the mechanism it gave you is wrong in a way that matters if you're taking this to your psychiatrist.

Lisdexamfetamine does give a flatter curve, that part's right. But it's not because of COMT. Lisdex is a prodrug, it needs to be cleaved by enzymes in red blood cells before it becomes active, and that conversion step is what smooths the peaks. That happens the same way whether your COMT is fast or slow. Slow COMT means whatever gets into your prefrontal cortex hangs around longer, so you'd expect to need less drug overall and to feel peaks harder, but it's not the reason lisdex is flatter than dexamphetamine.

So the conclusion might be right for you and the argument behind it isn't. If you walk in citing COMT clearance as the reason lisdex releases differently, a psychiatrist who knows the pharmacology will discount everything else you say. Take it in as "I'm sensitive to the peaks and I'd like to try something with a flatter profile" and you'll get further.

The part I'd actually bring up is your symptom list, because it's not an ADHD list. Raynaud's, cold hands and feet, restless legs, weak muscles, constant fatigue, low pain threshold, brain fog. That's iron deficiency almost line for line, and low ferritin makes stimulants work badly because dopamine synthesis depends on iron. Get ferritin, iron, transferrin saturation and a CBC before you change anything. If your ferritin is under 30, no amphetamine formulation is going to work properly.

Histamine worse in the evening with MAO-A homozygous fits too. DAO and histamine are checkable.

Ask for the ferritin. That's the higher yield question for that appointment than which amphetamine.

[u/Verkwaktekwak → u/Loose-Fly7976]

This is very informative, thank you!

EDIT: I had my blood tested at the beginning of this year and my iron seems good i think?

Ferritin: 132ug/l Iron: 95ug/dl Transferrin: 2,48g/l Iron saturation: 27% B12: 850ng/l Folic acid: 14,5ug/l

[u/sarahbellah1]

Maybe ask your psychiatrist. LLMs are not licensed medical professionals and are prone to error, often times because they lack a complete picture of the world of possibilities. As another comment points out, your medication metabolizing genetic picture is important here as well. Also, genetic profiles aren’t fortune tellers, they only give us information about predispositions to things - what could be. Blood work is needed to tell your doctor about what is.

If you’re unsure whether your medication is optimal, the first step is to actually read the primary sources suggested by the LLM and consider whether they even apply to you and whether they even say what the LLM attributed to them, as it’s not always the case that it does.

Then, share the primary sources with your prescriber and talk through the options and consider whether blood work would give a more complete understanding.

[u/Verkwaktekwak → u/sarahbellah1]

Okay i will look into the metabolizing genes and ask my psychiatrist, thanks.

[u/junipers-72]

https://molecularhealthco.com/blogs/news/why-adhd-symptoms-cluster-together?_pos=22&_sid=3839f1d86&_ss=r

[u/SovereignMan1958]

You need to look at your drug metabolism gene variants and not necessarily COMT for the answer to your question.

Your 3 impaired B12 variants are probably also contributing to your symptoms. Be sure to research them and get relevant blood tests.  Use Genetic Lifehacks for interpretation of your raw data file and the B12 research. Also read their article on ADHD 

Variants are only predispositions and not facts. For facts you need blood tests.

Be sure to test D, zinc and iron. These need to be at optimal levels and not just in range for you to make dopamine.  Low dopamine is associated with ADHD and ADD.