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SSRIs do lower the risk of further depressive episodes.

"To conclude, this review provides evidence that continuing SSRIs for 1 year reduces risk of MDD and relapse."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761909/

I took SSRIs for 14 months and after I stopped this was my subjective experience as well. (And luckily only mild withdrawal/discontinuation symptoms.)

That was exactly my first thought. We could definitely throw the SSRI efficacy into doubt though by sampling CS fluid or something for actual serotonin content in cohorts who are subjectively feeling improved by SSRIs.

It would also explain why SSRIs take time to work - as I understand it the SSRI action is immediate and yet it takes weeks for people to notice the effects.

SSRIs aren’t the only medication that requires weeks to work.

SSRI efficacy is already in doubt, as roughly 80% of the beneficial effects are replicated by placebos; some research has suggested that the remaining difference is due to the side effects, which make SSRIs active placebos and mess with study blinding.

And, even if they are better than just an active placebo, the mechanism is probably not the effects on serotonin levels. (Discussed previously here: https://news.ycombinator.com/item?id=32160703)

That would only throw into doubt SSRI efficacy for increasing serotonin levels. Not SSRI efficacy for treating depression.

Yeah the gut microbiome is the next big thing for sure. It should be easy to study. Food logs, mood logs, medication logs, next generation sequencing and maybe some metabolic profiling and we should be able to find interesting correlations.

I know my mood changes drastically down when I fail to eat properly for a period of time.

As if omics research isn't hard enough, there's a confounding layer of privacy and incentive problems.

From a science angle it makes more sense to just collect this data from everybody all the time and let the studies be post hoc explorations of that giant dataset. But how do you get people to cooperate when they have reason to believe that the data will be used against them (by third parties who end up with the data)?

Either we accept the diminished value of isolated study-at-a-time datasets (as we're doing now), we figure out how to do this kind of research through a layer of homeomorphic encryption (a tall order), or we wait for an era with more trustworthy institutions (potentially a long time).

For this reason, I think it'll be like fusion power: the perpetual "next big thing".

give out equity to the study participants. I'll hand over data of you give me some equity on future ideas built on that data. l Like artists getting payed royalties.

> Yeah the gut microbiome is the next big thing for sure. It should be easy to study.

It won't be. We aren't able to culture most gut bacteria. Most die immediately in oxygen.

The best we can do at the moment is correlation.

Good insight. I went through a profound burnout in 2019 after I lost my digestive health and got low serotonin due to a combination of work stress, overtraining at the gym, dehydration and a finger of booze after particularly hard days. Also food sensitivities to legumes, nightshades and almond butter, which I wasn't aware of at the time. I just learned that 25% of people who get food poisoning go on to develop IBS. Don't eat gas station sushi when you're on vacation!

https://experiencelife.lifetime.life/article/the-food-poison...

Ashwagandha basically restored my gut health in 3 months, in combination with psyllium husk capsules, kefir, and large plain lettuce salads with a vinegar-based dressing. My theory is that my cortisol levels got so high after decades of stress and negative reinforcement that I had symptoms like Cushing's syndrome. So ashwagandha mopped that up, which raises testosterone/estrogen and probably fixes a whole host of issues. But I never tested those levels, so take that with a grain of salt.

I've experienced the connection between gut health and mood, now I do everything I can to stay in good shape. But I've noticed a resistance to this line of thinking, especially in older people who just want a pill from their doctor.

Your are sensitive to plants from the nightshade family and you take ashwagandha? Either your ashwagandha doesn't contains active substances or you are not really sensitive to plants from the nightshade family.

> profound burnout in 2019 after I lost my digestive health and got low serotonin due to a combination of work stress, overtraining at the gym, dehydration and a finger of booze after particularly hard days. Also food sensitivities to legumes, nightshades and almond butter, which I wasn't aware of at the time

Ashwagandha is a nightshade, so you likely weren't allergic to nightshades if it helps.

Also, I'm not sure how you concluded that you have "low serotonin" due to gut issues. Serotonin in the gut doesn't migrate to the central nervous system. It serves different purposes throughout the body, but the synthesis in your brain remains local to the brain.

There are a lot of unrealistically specific claims in your post about cortisol and serotonin, but it's impossible to make such specific diagnoses. You might be reading too much into the alternative medicine world that misuses surface-level knowledge about hormones and neurotransmitters to provide false comfort. Real medical diagnoses aren't so specifically centered on singular chemicals.

Fair points, ya, I'm not disagreeing, and most of what I'm saying is anecdotal. My working theory right now is that food poisoning triggered an autoimmune response to something with my gut motility. Exacerbated by sleep apnea, stress, drinking, malnourishment from inflammation, who knows. Ashwagandha may have desensitized that somehow.

To be blunt, 2019 was one of the worst years of my life. I found myself out of work with no insurance and worse, no executive function. I went from loving my job and hitting gym PRs to broke and barely able to get out of bed in the morning. 20 years of trying to win the internet lottery and failing had sapped my motivation. Then the pandemic hit and things went from bad to worse to even worse to past the point of believability. But thankfully that series of traumas led to my conscious awakening and so I am grateful for that experience. And am gainfully employed and having fun with my work again, which is priceless. And hitting gym PRs again, which is frankly a miracle.

I guess I keep OCD'ing on this because working in tech is so high-risk that mental health issues are all but inevitable IMHO. But there are basic preventative steps we can do that western medicine seems reluctant to advocate for whatever reason. I have to be honest - without publicly funded healthcare, our system is garbage because it's being ruled by the profit motive and a tiny elite who spend their ill-gotten gains on lobbying to get out of paying their taxes. Their greed preventing win-wins like preventative medicine is just another hurdle for people on the edge, effectively talking them out of getting the care they need. Maybe the breadcrumbs I leave might help someone struggling to get just well enough to schedule an appointment.

I should add that I finally did go to the doctor and got some treatment, but they had trouble isolating any specific cause. I feel that the everlywell.com (no affiliation) food sensitivity test I took and dietary changes were the main fix, YMMV.

Most SSRI doesn't do much. The ones that work seems like related to dopamine metabolism. SSRI aspect is already debunked. Fluoxetine for example works and i think additionally confirmed by dramatically increased mortality since depression should decrease mortality which is why it exists.