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“No convincing evidence” that depression is caused by low serotonin levels

bmj.com

331–340 of 625 posts

Re: “No convincing evidence” that depression is caused by low serotonin levels

#331

Earlier quoted context omitted.

Same here, but with Fluoxetine (Prozac). However, I don’t think exactly that fluoxetine made me less depressed. It only made me more „aggressive“ and more risk taking, and the antidepressing effect came from the positive results of taking such risks. I just „don’t care“ about failures as much as I used to. E.g. I finally started talking to girls, because I wouldn’t care about rejection that much. => Got into my first…

Shit I need pills that do the opposite lol.

I have ADHD, frequently exhibited risky behaviour, ADHD medication (MPH) reduced this effect for me, I'm more conscious and think things through before they happen.

Re: “No convincing evidence” that depression is caused by low serotonin levels

#332
post #184

Earlier quoted context omitted.

I love reading medical advice on HN. Genetic errors which cause high LDL levels result in significant cardiovascular disease. It's a very strong cause and effect. I won't argue that inflammation doesn't play some role (it seems to play a role in many diseases), but I wouldn't dismiss current medical opinion on LDL. https://en.wikipedia.org/wiki/Familial_hypercholesterolemia Familial hypercholesterolemia (FH) is a gen…

Why aren't you adjusting for LDL subfractions? Seriously, yes having too much LDL can be a sign of having harmful subfractions but that doesn't mean high LDL actually is harmful or low LDL is healthy.

I'm not sure that changes my argument than "There's no such thing as good / bad cholesterol." is a false statement?

Re: “No convincing evidence” that depression is caused by low serotonin levels

#333

Earlier quoted context omitted.

Have you considered that your comment may have been downvoted because you come across unnecessarily hostile, not because of some absurd attack on your person? Similarly, any space is a good space to discuss and spread awareness on mental health — even if only one person finds an idea to help them, whatever their situation may be, it's already a massive positive.

> because you come across unnecessarily hostile And possibly justified. A lot of us are armchair psychiatrist from reading articles. OP that you're replying to lives this type of medication and attributes being alive right now to it while a lot of us who have only read articles sit and debate. A number of these comments can come across as "just eat healthier" to an overweight person or "don't be sad".

[deleted]

Re: “No convincing evidence” that depression is caused by low serotonin levels

#334
post #120

Earlier quoted context omitted.

> the pop-culture misunderstandings about "low serotonin" Let’s be clear though, I had an actual licensed psychiatrist say this to me last week. It’s not like people are getting this “pop-culture” information via blog articles…

It's possible the psychiatrist is using "low serotonin" as a simple shorthand meant for the layperson

I had a medical doctor describe the benefits of SSRIs with: "these pills will increase the happy chemicals in your brain".

Re: “No convincing evidence” that depression is caused by low serotonin levels

#335
Yeah, but thats hardly news, we have known that for decades. Otherwise direct serotonin releasers would be the most useful ADs. But these mostly give people nausea and serotonin syndrome. ADs work mostly by being FIASMAs, reducing inflammation and oxidative stress, increasing neurogenesis and neuroplasticity, increasing the activity of other monoaminergic systems, and the serotonergic portion is mostly explained by downregulation of 5-HT1A autoreceptors due to chronicly high extrasynaptic 5-HT levels. This also explains the delayed action of ADs.

At least this is my knowledge from when I last researched this topic in depth.

But that would be a little bit too much for the general public, so it is simplified, to this annoying effect that everyone talks of "low serotonin levels" where in fact the underlying systems are way more complex.

Re: “No convincing evidence” that depression is caused by low serotonin levels

#336
> Other clinicians say, however, that the notion of depression being because of a simple chemical imbalance is outmoded anyway, and that antidepressants remain a useful option for patients alongside other approaches including talking therapies.

This is the key line in the summary.

The concept of attacking an idea no one really believes is really a straw man.

More importantly the modern practice of medicine is "evidence based medicine", not "mechanism based medicine". That means treatments are tested as to if they work, not how they work. Ideally in multiple well run double blinded randomised controlled trials with at least some against treatment as usual. Unlike the past when we thought more about how they might work, theorising something is off about someone's humors and adjusting with leeches.

Anyone looking for a truly mind bending result should look at Hjorth et al. 2021 [0], the study recruited people with social phobia and gave them all an SSRI (escitalopram). Half were told they were getting a sham active placebo and "should not expect to get better", half were told "you're getting the known effective treatment".

Headline result being told you are being treated leads to 4x as much response with brain changes in the dopamin networks.

In the meanwhile, rather than worry about how antidepressants work, why not take a look at electroconvulsive therapy which has proven time and again to be the most effective treatment for depression. Yet we have no idea how it works, other than knowing a decent seizure in those without epilepsy makes you less sad? What on earth.

[0] https://www.nature.com/articles/s41398-021-01682-3

Re: “No convincing evidence” that depression is caused by low serotonin levels

#337

> Other clinicians say, however, that the notion of depression being because of a simple chemical imbalance is outmoded anyway, and that antidepressants remain a useful option for patients alongside other approaches including talking therapies. This is the key line in the summary. The concept of attacking an idea no one really believes is really a straw man. More importantly the modern practice of medicine is "eviden…

> are tested as to if they work, not how they work

Should they be doing both? I can't imagine shipping code that I don't know how it works, but it passes tests...

Otherwise, you'll get pseudoscience - just mix random chemicals and see how patient reacts, rinse and repeat until something works...

Re: “No convincing evidence” that depression is caused by low serotonin levels

#338
post #274

Earlier quoted context omitted.

Sadness or distress vs not feeling anything and not having motivation?

Yes, this is roughly in the right area.

I wonder how a week of low dose amphetamine usage, like adderall, might help disrupt no-motivation mood loops. A friend of mine (cycling through many antidepressants) seems like he would respond well to this. As in, he would feel better and be able to “shift gears.” Not to get more work done, but say, enjoy going to an art museum. And feel what it is like to be enthusiastic again.

Re: “No convincing evidence” that depression is caused by low serotonin levels

#339

> Other clinicians say, however, that the notion of depression being because of a simple chemical imbalance is outmoded anyway, and that antidepressants remain a useful option for patients alongside other approaches including talking therapies. This is the key line in the summary. The concept of attacking an idea no one really believes is really a straw man. More importantly the modern practice of medicine is "eviden…

> are tested as to if they work, not how they work Should they be doing both? I can't imagine shipping code that I don't know how it works, but it passes tests... Otherwise, you'll get pseudoscience - just mix random chemicals and see how patient reacts, rinse and repeat until something works...

> shipping code that I don't know how it works, but it passes tests

We call that machine learning

Re: “No convincing evidence” that depression is caused by low serotonin levels

#340
SSRIs appear to work through the vagus nerve in a similar way to psychobiotics. Their direct effects on neurotransmitters are probably an unwanted side-effect:

Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling (2019): https://www.nature.com/articles/s41598-019-50807-8

Identification of SSRI-evoked antidepressant sensory signals by decoding vagus nerve activity (2021): https://www.nature.com/articles/s41598-021-00615-w

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