The serotonin theory of depression: a systematic review of the evidence (2022)

A fairly surprising fact revealing how little we understand the efficiency of SSRIs is that the serotonin level rises pretty quickly once you have started taking an SSRI.

Still, there is an unexplained cascade of reactions that takes weeks before patients notice any improvement.

As much as I respect proof-based medicine, the very fact that scientists can't explain how all this works made me want to stop my treatment and just do more weightlifting and running.

>how little we understand the efficiency of SSRIs

A drug that is taken by millions of people, if your take is that we understand it too little, either you are deep enough in the subject to make some interest questions, or you are missing the forest for the trees.

I'm not sure how useful it is to keep investigating exactly how it works on a chemical level, yeah for sure some people should look into it, but in the same way that some one should do 1600m in the regional competition of Minnesotta, as a niche.

You can observe the effects of the medication on people, done.

I remember seeing a video on a cannabis researcher explaining that they didn't find any difference between the indica and sativa strains for example, and she talked about chemical properties. Just get 10 people to smoke one or the other and you are done.

There is such a thing as overintellectualizing, and FUTON bias isn't a particularly impressive way to do it.

There's actually far more research into what happens after starting an SSRI than you're implying. We know, for example, that certain downstream adaptations takes weeks to fully appear. We also know that the initial increase in serotonin concentrations is limited by 5-HT1A negative feedback, but 5-HT1A downregulates over time and allows the synaptic concentrations to increase again.

> the very fact that scientists can't explain how all this works made me want to stop my treatment and just do more weightlifting and running

Weightlifting and running are complimentary, not substitutive. Most people can't simply replace a powerful medication with more running and weightlifting.

You might also be surprised at how many modern medications operate on partial theories. There's not actually anything wrong with that. There are a lot of medications that hypothetically should work based on scientific understanding of the brain but don't seem to show efficacy in studies.

It's more important that we validate the safety profile and efficacy in real-world testing.

I am not saying that quitting SSRIs is the ultimate answer, it just works (sort of) for me mostly because I am not that depressed.

Also, having partial theories is not wrong, but in the case of SSRIs, I deliberately chose to avoid medications that I can do without (again, this is highly subjective).

Another concern of mine is that there are now warnings for some popular SSRIs that ED symptoms in men might be permanent.

> Another concern of mine is that there are now warnings for some popular SSRIs that ED symptoms in men might be permanent.

They are for some of the unlucky 10%. Buspirone might help.

> "I'm not sure how useful it is to keep investigating exactly how it works on a chemical level"

It has the potential to be incredibly useful.

Not because there's a benefit to being able to tell patients "this is the technical explanation of how the SSRI we're giving you will help", but because we currently don't have a perfect treatment for depression, and understanding how existing imperfect (but useful) treatments actually work might lead to either creating better SSRIs that are more effective, or to creating non-SSRI treatments that we haven't yet thought of.

>treatment for depression

That reads like a treatment for death, or a solution to poverty.

Will you find the answer by doing 100 metastudies and taking advanced chemistry. Or will you find the wisdom by meditating and talking with your dad and priest.

So I'm either an anti-intellectual, or you are a super-lectual.

You should know that there are plenty of common drugs where we have almost no idea how they work. Perhaps the most surprising is metamizole, sold under brand names like Novalgin, Analgin, Algocalmin. One of the most common over-the-counter low grade pain meds and fever meds in the world, and yet we don't know the precise mechanism of action.