I'm on an SNRI that reacts badly, in my body at least, with just about everything (everything else acts like a sponge). Is there a chance of T doing this or are there any type or way of administering T that would be less likely to react badly/don't have weakens SNRIs as a possible side effect?
I don’t think that any commonly used form of testosterone-based HRT would affect SNRI absorption. I’m basing this statement on a couple things that I’m going to write out not because I want to convince you, but because you know your meds better than I do and you can find potential holes in my justifications. (I’m also undercaffeinated, please bear with me.)
First point: Usually, things that reduce the efficacy of an antidepressant do so because they either impact your ability to absorb the medication in the first place or because they stop you from effectively metabolizing it. The former pathway is why, for example, you’re sometimes told not to eat fatty foods at the same time as a medication—your stomach is essentially so busy absorbing that food that it slows down the medication’s entrance into your bloodstream, and you may not get as much of the medication. Conversely, sometimes you’re told to only take your meds with a meal, because slowing it down like that helps you avoid side effects like nausea. Zoloft, for example, is kind of infamous for needing to be taken with food, and you’re supposed to avoid fruit juices with ADHD medication because acidifying your stomach even just that little bit makes it harder to absorb stimulants.
The latter pathway, metabolizing problems, is… really complicated. After you absorb a medication from your stomach, various enzymes in different organs break it down into metabolites; the most common pathway is through your liver. Some psych medications can inhibit different enzymes, either competitively or non-competitively (here’s a good explanation of that). This can prevent you from effectively breaking down the medication, which increases your circulating levels—if it isn’t getting broken down, it just stays there, and can build up quicker. A really good example of this is Luvox, which inhibits a TON of enzymes (link goes to Wikipedia) and thus has a lot of really weird interactions with other medications. It makes coffee last forever.
In the SNRI area, Effexor is also a good example of this because it’s unusual—its metabolites also function as SNRIs, so it works roughly the same between patients who have certain enzyme mutations (CYP2D6, specifically) that make it hard for them to absorb a lot of psych medications. Different people produce different amounts of CYP2D6, but Effexor kind of skips over that variation. Think of it like a slime cube. CYP2D6 is your sword. If you cut the slime cube in half down the middle, it just makes two smaller slime cubes. Luvox, by contrast, is like a rock giant. It’s super hard for your sword to cut that in half, so when more rock giants show up, you can’t fend them off. Most medications are rock giants, or ogres, that are hard to cut in half.
So, second point: Testosterone that we take via HRT isn’t metabolized in the same ways that most psychiatric medication is. It uses different enzymes, and it’s metabolized into other androgens, like DHT, and into estradiol. A small amount of it does go through enzymes that psychiatric meds use, but we don’t actually have any evidence to suggest that the interaction is significant—that doesn’t mean one can’t exist, but just that it hasn’t historically been a significant enough interaction if it does to warrant in-depth study.
What we do know about this is that antidepressants aren’t considered to be significantly different in action between “women” and “men”, meaning cis perisex people with normative endogenous hormone profiles.* There’s also no particular advisory given to people starting T that says you should avoid or adjust dosages of antidepressants, apart from the standard “tell your doctors about all the meds you’re on” warning.
Third point: I also don’t think that absorption through your stomach would be significantly impacted by T for a couple reasons. First, most people on T aren’t on an oral form—pill testosterone has been largely phased out for a lot of complicated reasons, and it’s outright inaccessible in many countries. The dominant forms of administration (injection, patches, gel, pellets) all release T directly into your bloodstream. Injections create sterile pockets of oil in your muscles or subcutaneous fat, which gets sucked into your blood over time. Gel and patches are both transdermal, and absorb into your capillaries. The pellets release their payload into subcutaneous fat over long periods—it’s slower because it’s solid, IIRC. The end result of all of these is the same, which is why we say there’s no difference in how fast you go through ~T Puberty~ based on administration method; once it’s in your blood, it circulates to your liver and throughout your body tissues, where it’s metabolized.
I do also think that you should ask your prescribing psychiatrist about this, if you’re in a position where it’s safe to be out as trans to them. This may be outside of their wheelhouse but they can track and moderate your SNRI dose most appropriately when they know all the other meds you’re on. You could also ask a pharmacist when you pick up your meds; they will likely say to ask your psych, but pharmacists are great and often know medication interactions offhand that psych professionals don’t. I’m couching my wording a bit in this answer because I’m not a medical professional, just a psych student who’s been on a bunch of different meds, and I’m guessing a lot about what could be going on for you that may not be accurate at all. But hopefully some of it is helpful, regardless?
TL;DR: If the reason that your SNRI reacts badly with other meds is because of something funky in the enzyme area, testosterone should bypass most of the pathways actively occupied by your SNRI. If it’s because of a problem in your gut, every form of testosterone that is not the pill avoids this completely. Either way, I don’t anticipate that your SNRI will interact significantly with testosterone, regardless of administration method, and you should be all good.
* There IS a legitimate point to be made about how psych meds tend to be tested on and “calibrated” for cis perisex men. That’s a little outside the scope of this post, though, and likely isn’t relevant anyways because we’re talking about adding testosterone to bring you to the hormonal profile of one of those test subjects.