TRT + SSRI (Viibryd) = Increased E2?

I am on TRT and I have recently been prescribed Viibryd, an SSRI antidepressant. This question is for those with more advanced pharmacology knowledge.

I have found that Viibryd is metabolized primarily by the CYP3A4 enzyme pathway in the liver. After research, I also found that estradiol is also metabolized by this pathway.

I have spent a lot of time finding the TRT dose that keeps my E2 in check, after nearly 2 years on it… and I have real concerns that taking this SSRI drug could cause inhibition of this enzyme and thus E2 metabolism and send me into the world of high E2 levels again. This is the last thing I want to be dealing with again, as it takes months of blood tests and experimenting to correct this once it gets out of check.

Does anyone know how much of a concern this is? I know that blood work will tell me, but I’d like to know ahead of time if this has the potential to screw me up. Maybe I need to find another SSRI (though in the past, Viibryd has been the most effective with the least amount of side effects, while others give me all kinds of trouble). Insights anyone?

You have the facts right but do not know the impact.
Vilazodone - Wikipedia
Vilazodone - Wikipedia

Not a very friendly drug.

Impact: Have you ever been on a SSRI before? It rewires your brain and when you stop taking it it can be a tough number of days. Might be better from a sexual function point of view, but Wellbutrin is too without any of the classic negative effects of SSRI’s.

Can we see current labs?
Do you have thyroid labs?

Please eval overall thyroid status via oral body temps - see below.
Thyroid does have a big impact on mood and energy when non-optimal.

Have you looked at other things like nutrients and supplements that might have an impact on your general wellbeing?


Please read the stickies found here: About the T Replacement Category - #2 by KSman

  • advice for new guys - need more info about you
  • things that damage your hormones
  • protocol for injections
  • finding a TRT doc

Evaluate your overall thyroid function by checking oral body temperatures as per the thyroid basics sticky. Thyroid hormone fT3 is what gets the job done and it regulates mitochondrial activity, the source of ATP which is the universal currency of cellular energy. This is part of the body’s temperature control loop. This can get messed up if you are iodine deficient. In many countries, you need to be using iodized salt. Other countries add iodine to dairy or bread.

KSman is simply a regular member on this site. Nothing more other than highly active.

I can be a bit abrupt in my replies and recommendations. I have a lot of ground to cover as this forum has become much more active in the last two years. I can’t follow threads that go deep over time. You need to respond to all of my points and requests as soon as possible before you fall off of my radar. The worse problems are guys who ignore issues re Thyroid, body temperatures, history of iodized salt. Please do not piss people off saying that lab results are normal, we need lab numbers and ranges.

The value that you get out of this process and forum depends on your effort and performance. The bulk of your learning is reading/studying the suggested stickies.

Thanks for the reply KsMan. Yes, unfortunately, I have been on nearly every SSRI out there. I was put on them as a teenager by a doctor and I do regret ever having touched them. I do believe they’re the reason I ever needed TRT in the first place. I have been on Viibryd before (and literally almost every psych med out there over the past 20+ years). I have also tried Wellbutrin several times over the years and found it to be completely ineffective. I have only been off of psych drugs for the past 2 years and I have constant complaints from those close to me that without them that I am extremely irritable, pessimistic, I have a fast temper and I generally have trouble enjoying life at all. I hate to admit it, but it’s all true. I have been unable to enjoy my life those past 2 years. I’ve been just existing because that’s what I’m supposed to do.

My labs are perfect. It’s no longer a question of hormones. My T levels are 700 on trough day, and estrogen is at 22-26 on my frequent blood tests. All other factors like cortisol, vitamin D, thyroid and so on are ideal. I have been to multiple endocrinologists that all reviewed full blood work and say everything looks fantastic.

This is a neurochemical/psych issue, I’m afraid. I was on high doses of SSRI’s and benzos for over 20 years and yes, I am very aware of the withdrawals and side effects. After nearly dying from benzo withdrawal 2 years ago, SSRI withdrawal is nothing to me anymore.

With that being said, I think that is why I have seen TRT not work for me, even after 2-3 years on it and changing all other aspects of my life to be ideal (diet, exercise, sleep, etc). There is simply no other avenue to pursue.

I can tell this is what it is because only after a few days on the SSRI again, I feel the intense brain fog and crippling lack of energy that I have experienced since going off of them lifting dramatically. My mood is up and my irritability is drastically reduced. I always thought it was something was wrong with my health still. Turns out, it seems my brain no longer functions normally because it has experienced permanent changes from these drugs over the decades. I seems it needs them just to feel healthy these days. It’s a shame, and yes, I do discourage anyone who doesn’t absolutely need them to stay the hell away. I can also say it’s not placebo effect because I was in denial that I needed antidepressants, didn’t think it would make a difference, and have been avoiding them for a long time. It seems I was wrong. I can’t deny the positive changes. Why did I choose Viibryd? It is the most effective for me, it works fast, and has almost no side effects for me.

That being said, I need to know how much this will affect my TRT. I am not on Arimidex anymore and I have not needed it since getting my T dose right. (120mg/week). I really want to avoid needing it again, but we both know if the SSRI ends up driving my E2 up, it could negate any benefit gleaned from the SSRI until I spend the months trying to get it all in check again.

Been on Klonopin prior to a few years ago for 30 years and is the reason I need TRT, these drugs rewire the brain over the long term and cause pituitary disorders. If safe to assume it could change the brain in a way that would make TRT less effective.

Have you tried pregnenolone, the brain hormone? It can help some with anxiety if you’re deficient. It was largely ignored years ago do to the fact it’s a hormones and can’t be patented and SSRI’s to over the spotlight do to being patentable which makes it a money making drug.

I believe my testosterone deficiency was caused by SSRIs, however the way I feel off SSRIs/SNRIs is the same as I remember from 5 or 6 years old - angry, obsessive, irritable, depressed.

Maybe it’s not a case that you need the SSRI because the drugs have created a dependency, but that you just need them because of neurochemical imbalances that have always been there?

Interestingly enough, Klonopin was the same benzo that I was on for 15 years. A hefty 8mg a day (yes, really). I believe, like you, that it has done some permanent damage, that wasn’t made any better by the cold-turkey withdrawal and subsequent seizures I had due to it. I didn’t go cold-turkey on purpose, it was due to my doctor denying me renewal because I was in another state and couldn’t come to see him for a visit. Should have been a malpractice suit there.

I have not tried pregnenolone, but did look into it at one point. What do you know about klonopin and the pituitary? I also have other pituitary problems like excess growth hormone, but they can’t find any tumor. You make me think…

Please tell me more about what the connection is here. I have found that TRT just didn’t have any effect for me, even though my levels were 250. I never thought about klonopin being related to that, though I do relate it to my overall poor health (mental and physical).

Mrmeeseeks, very possible, as I obviously went on the drugs for a reason. I had EXTREME anxiety as a teenager, to the point where I had social anxiety so bad I was a recluse. I also had severe depression back then.

The reason I didn’t think I needed SSRIs is because after going off of them, I felt I was “ok enough”- meaning I had gotten my life to s good place (good career, good relationship, etc) but I still don’t feel happy or interested in anything. My girlfriend complains I am constantly irritable and I never want to do anything but lay in the bed all the time. She is right. I have no life in me. I guess I got so used to accepting that was the best I was going to get that I haven’t even realized I might really be depressed. As men, I have read that many times we manifest depression as anger outbursts or irritability as a “more socially acceptable” alternative to showing weakness or sadness. I have had some rage outbursts lately that are totally against my personality. This is what sent me to these drugs again. I feel I’ve been losing control of myself and I’m angry all the time.

Holey shit, 8mg! I was on 2mg daily for 30 years and my testosterone levels were fine the entire time, until my doctor instructed me to start tapering off, she gave me no choice as they are studies showing permanente pituitary damage as a result of taking these benzos long term.

The damage was caused when I began my slow agonizing 10 month withdraw which saw my testosterone levels plummet! A year later I scored a TT of 225 ng/dL, .72 ng/dL and E2 levels undetectable. Complete muscle atrophy, anemia, diabetes as a result of falling testosterone.

TRT putting my diabetes into remission.

I had very bad social anxiety that kicked in when I was 16 & was worst by about 24.

Yeah there’s that, plus my experience is that I spent so many foundational years as a recluse, that I stopped maturing emotionally.

My experience is that for quite some time I only had a couple emotions - anger & fear - everything manifested as anger or fear.

I started to get better when I surrounded myself with people with lots of emotional intelligence & talked about feelings. I met those people through volunteering in the mental health & homeless outreach sector.

I learned everything I know there, really.

As well as you having had those years in reclusion, I usually see that if someone has been a long term user of psycho active drugs - in your case Benzos (but could be opioids, alcohol, street drugs) - that stops complete emotional development for all the time they are used.

I don’t mean that in a critical way, far from it! It is the stuff that needs to be talked about & the toughest men I know - long term armed forces - are rigorously open & honest about emotions & fear - because pride would get them killed.

So what I’m saying in a long winded way (!) is a counsellor you could see regularly for maybe a year or two - you’ve got a lot of years to unpick - could be a good idea.

In the good old days people needed village elders who were mentors & who knew a lot about life. It’s the same thing & it’s a strength to be willing to learn from others. It’s also a real strength to be willing to face unpleasant feelings & memories - a lot of men choose to run from that shit.

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Thanks for that insightful reply. I think you’re spot on. It’s funny because I have always been a person with high emotional intelligence. I’m a very caring and friendly person. Very well liked. I think my issues here came from a childhood where I was always put down by a stepdad and never felt good enough. I never developed any self confidence. It was made worse when I entered high school and I was shy and quiet, along with being a late bloomer. I was always a skinny twig that never could get a girl to look at me. In high school or college. That takes a huge toll on one’s confidence especially when it’s already non-existent. It did some real damage to me. I know this. Strange thing is, I’m apparently a very attractive guy. As an adult, women loved me- until they found out how timid I was. Big turn off, obviously. I used (a lot of) drugs through my 20’s and 30’s to make me feel happy. I’m paying for it these days in my late 30’s.

I know a lot of damage also came from all of the long term relationships I have had. I had 4 of them as an adult and they all ended up cheating on me. One I was with for 7 years got pregnant by my best friend while she was living in my house. Double betrayal. That sent me into another bout of being a total recluse for 5 years from 28-33. I was incredibly lonely and I still have trouble with my current 2 year relationship due to these past experiences.

All in all, you’re right. I have a LOT of deep down emotional issues that have never been talked about or resolved. I do not have anyone to talk to, and I cannot talk to my current partner because I know she will devalue me and end up leaving me too if I showed any weakness or emotional side. Sadly that’s the way I feel all women are. Maybe not, but in my mind I can never be myself fully. I have to put off this fake persona of strength and invulnerability when I’m anything but. I’ve made INCREDIBLE progress in my life the past 2 years (since getting off of drugs) like you wouldn’t believe. I have so much to be proud of, and I am, but that hurt young man will always pull me down.

I do need counseling. I have considered this before, but the ones I have been to long ago didn’t help me. They just listened and had no real insight to help me move on. That may be why I just spilled my guts here, sorry about that, lol.

I wish I could talk to you privately to get some advice of how you found your way into these helpful avenues, but I don’t think you can PM on here. But thank you for your suggestions. I will seriously take them into consideration as you seem very wise and I appreciate your help, my friend.

I wish I had ever been to a doctor like this. It could have helped me long ago. All doctors I have been to seem like they barely passed medical school and I don’t know how they’re doctors when I am talking above their heads. One didn’t even know testosterone was converted into estrogen. I asked him to test my estradiol and he asked me why a man would test that! No kidding! The rest just put my legit concerns off because I feel they’re confused by what I’m saying (in a technical sense, even though I know it’s correct). It’s so hard to find a good doctor. I’ve been to 2 endocrinologists, one at a MAJOR hospital who is supposed to really know his sh*t and he saw no connection between 15 years of klonopin use and a dysfunctional endocrine system. He just said “nah, that wouldn’t cause hormonal problems, you’re barking up the wrong tree…”

Wtf. This is the overwhelming rule, not the exception.

Lots of similarities there mate & thanks for being so open. Loads of stuff in there.

Growing up my parents only had a few emotions - anger, fear or stressed - I was very afraid of my dad’s temper until I was about 20 years old.

I was verbally bullied a lot by my older brother - daily criticisms of my appearance - mostly that I was skinny or a facial feature was ugly, then when I filled out, that I was fat. It didn’t take much for me to believe what he said, and I thought I was painfully ugly.

I was a recluse for years as well.

Like you, looking back at my teenage photos I was a really good looking kid ! What I was told was all horse shit!!

I’ve done a lot of counselling around those relationships & also talked to a lot of friends in my area of work - homeless/prisoners/substance abuse.

What I’ve come to understand is that my parents seem to be typical baby boomers - which is to say their parents had poor emotional intelligence, were cold, detached, had no interest in my parents - ill equipped to be parents - so they learned poor parenting.

I didn’t realise it until I examined it with a counsellor, but my brother was bullied a great deal at school & he was in a terrible place himself. He took that out on me. “Hurt people hurt people”

From examining all this with a good counsellor, I’ve been able to let go of my resentments towards my parents. That’s very liberating mate.

I’m still working on how I feel towards my brother. That’s a work in progress!

I’m very sorry to hear about what happened with your 7 year relationship & your friend.

Like you’ve said, I used to think being sensitive was a weakness. I wondered why I felt like shit if I treated others badly, treated women badly and slept around, why I felt bad half swindling someone as a salesman.

Today my belief is that having a conscience, being sensitive & having a moral compass are strengths. I had it all backwards. Being sensitive allows you to see, hear & be aware of loads of stuff others can’t often see. It allows you to do good in the world, instead of just taking.

If you put the work in with the counselling, you’ll become & have things you couldn’t imagine. You’ll possibly be very different to the person you want to be right now, but my experience was first accepting I wouldn’t be exactly how I wanted to be - my introversion won’t go away - to gradually caring less & less about stuff like that - to becoming quite content in my own skin.

My experience with women (and the world) has been every year it’s like another layer of a blindfold is removed - I can spot good women, women who are spiritually sick, women who have a lot of shit going on. By and large, so far I can avoid hooking up with women who are bad news. I’ll probably screw up there though haha!

I tried ‘talking therapy’ as well & didn’t get anything from it.

I was lucky with the 6th psychiatrist I met - he was the one who prescribed TRT. He said I need a counsellor with a spiritual approach, he was right! It took 2 years & a lot of it was CBT as well.

You could try looking for someone like that.

I’d definitely recommend finding communities with a spiritual/self less outlook as well - volunteering then working in an area which I found meaningful did that for me. Some of those people are incredible. I’d never ever met people like that before.

I often feel I’m lucky to have a new, second life, a lot of people only get one life. You might come to believe that too. Other days I get fu*ked off that I’ve got to work quite hard to stay mentally fit, haha.

Hope that’s food for thought :slight_smile: It’s not my wisdom, I’m just repeating what was taught to me.