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

bmj.com

391–400 of 625 posts

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

#391

The book lost connections is a really good read on this. It points out the problems in modern society and our lives that lead to depression rather than it just being something that can be solved with a pill. Things like our lack of connection to meaningful work, our lack of connection to each other and our lack of connection to nature all play a big part.

There's also the driving our novelty seeking brains into overdrive with all kinds of artificial stimulants, including this very forum.

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

#392

> 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…

Most effective treatment for depression = psychedelics. They have been used by shamans for eons for this reason. A lot of modern research into this (including 1000s of research studies from the 50s and 60s) confirms it. It was only because Nixon didn't like the fact that kids were not going to war, that the war on drugs was started.

Please do not assert pet theories as established scientific consensus or fact.

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

#393

SSRIs raise extra-synaptic serotonin levels within the first hour of taking them. However, their efficacy against depression takes weeks or even months to manifest. We've known this for decades, and as a result the "chemical imbalance" theory of depression hasn't been a real contender in depression research for a long, long time. The key thing to understand is that serotonin levels don't have to be low for SSRIs to i…

I think you’re throwing the baby out with the bath water here. Sure depression may not be linked to low serotonin levels but it almost certainly some chemical imbalance of some variety.

That's vague enough to be a totally useless description. Dehydration is also a "chemical imbalance of some variety".

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

#394

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 d…

And now the opposite happens with headlines that imply "your medication is suddenly revealed to be useless" when in fact we've been aware that we don't know how it works for a while, but we're still reasonably sure it helps, which perhaps explains the increase in prescription more than the "serotonin is the only thing that matters" theory which the experts ruled out a while ago.

They barely work better than placebo, from what I saw in my reading of the literature.

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

#395

> 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…

> why not take a look at electroconvulsive therapy ... Yet we have no idea how it works ... Or you can stick with something that has been already been scientifically studied and proven to be as effective as anti-depressants in curing depression - Cognitive Therapy. In fact, it even prevents relapses more than anti-depressants: > Depression is one of the most prevalent and debilitating of the psychiatric disorders. St…

It’s not an either/or scenario. CBT is recommended already for pretty much all comers. ECT is last line in treatment refractory MDD.

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

#396

The book lost connections is a really good read on this. It points out the problems in modern society and our lives that lead to depression rather than it just being something that can be solved with a pill. Things like our lack of connection to meaningful work, our lack of connection to each other and our lack of connection to nature all play a big part.

Sounds like Kaczynski’s “power process” in Industrial Society

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

#397

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 d…

Anytime I learn about bodily functions I become more and more aware of how shit it's engineering is. Works amazing, sure, but try and fix or debug anything? Good luck.

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

#398
post #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): ht…

recently procured an acupressure spiky foot ball that was originally designed to combat depression by stimulating the vagus through the foot. I don't consider myself depressed by any means, but after a few minutes of rolling my feet aggressively over the ball and targeting a few key areas, I generally feel much better and can actually sense that my body is less stressed. everyone should have one or 2 of them

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

#399

Earlier quoted context omitted.

And now the opposite happens with headlines that imply "your medication is suddenly revealed to be useless" when in fact we've been aware that we don't know how it works for a while, but we're still reasonably sure it helps, which perhaps explains the increase in prescription more than the "serotonin is the only thing that matters" theory which the experts ruled out a while ago.

They barely work better than placebo, from what I saw in my reading of the literature.

I’ve tried a number of antidepressant drugs and so far not been able to notice much difference with any of them.

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

#400

Earlier quoted context omitted.

It's a shame that the imagining is so expensive, because I'd love to see a true control arm with placebos and follow up scans. i.e. if you are on a placebo and are told you will get better how many do?

Don’t they do truckloads of tests and comparisons on anti depression medicine all the time including blind trials etc?

The interesting bits, for me, are the imaging scans which are expensive and slow and you need more than one for comparison per subject.

Secondly the 'covert treatment' aspect, and as far as I know only Hjorth et al. do in any reasonable numbers is the giving someone the treatment and usual and tell them it's a placebo and they "shouldn't expect to get better".

It's ethically tricky to do that with an anxiety disorder but I imagine a doctor telling someone with depression that will be painfully close to "you're not getting better", "we're not going to help you" and other quite rejecting disheartening ideas.

But plain placebo controlled SSRI trials I think show about a 0.2 absolute benefit in SSRIs in depression. i.e. if you compare SSRI with placebo you need to treat 5 people with SSRI to see one more person respond. If you compare SSRI with no treatment, you only need to treat 3 people with depression, to have 1 more respond. Those 3 and 5 are called the 'number needed to treat' and can be compared to the 'number needed to harm'.

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