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

bmj.com

401–410 of 625 posts

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

#401

When you look into the studies for antidepressants, the track record is abysmal. They’re not innocuous, trigger serious side effects, some are hard to quit, but more importantly they only make a difference in people with extremely severe depression. And doctors often downplay or don’t mention side effects honestly because they don’t want patients to not take them. The studies justifying antidepressants as effective t…

Yeah an unregulated and uncontrolled consumption of a poorly dosed hallucinogenic is totally better than a double-blind study of SSRI/SNRI. I swear, I do not reject the possibility that hallucinogenics can cure depression better than existing meds, but the almost religious enthusiasm for such a poorly studied chemical is deeply concerning. And yes, before you accuse me of being a pharma shill, I know that the lack of…

Careful: whether SSRIs and SNRIs work is unrelated to whether hallucinogenics do or don't. hallucinogenics being shit doesn't make SSRI/SNRIs a good bet.

Also, those exact studies you refer to show that SNRIs work very poorly and are very limited.

Usually studies have fewer than 100 participants:

* people are dropped from the study arbitrarily

* they are not double blind

* they are not representative of the population (overwhelmingly participants are white, male, well off or young with no other health complaints and few serious problems)

* studies are usually very short (They then find drugs are less than 15%ppts more effective than placebos. In exchange you get quite extreme side effects for a significant number of users from impotence to suicide...

The lancet picked this up and did. meta-study. Their conclusions:

>We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72–0·97) and fluoxetine (0·88, 0·80–0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01–1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

I think even assuming good faith for all those studies, those are poor results when you include the low acceptability. If you don't assume good faith you're left wondering if these drugs work at all.

It should go without saying that NO ONE should stop or change their medication (especially highly addictive ones like these) based on a HN comment. Please speak to your doctors dear readers.

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

#403
post #370
post #350

Earlier quoted context omitted.

Please don't post offtopic flamewar comments, regardless of how wrong other people are or you feel they are. It just makes everything worse. Also, please don't go on about downvotes. That's in the site guidelines too: https://news.ycombinator.com/newsguidelines.html Edit: I assume you're talking about https://news.ycombinator.com/item?id=32161183 , which was correctly downvoted for being a flamewar comment. Please do…

Why is this an off topic flame war comment but “I’m too tired to write a paragraph but SSRIs kill” is fine? The moderation here rewards engineer’s disease where we first principling our way to warning people to ignore Dr.’s suggestions as long as everyone’s smiling at each other. It’s like an anti-vax YouTube video where any dissenting opinion is flagged until mods give up and remove it from the front page. It’s the…

Yes, that was also a bad comment. It wasn't aggressive to other users, though, which is an important difference from a moderation point of view.

HN is an internet watercooler. People come here to have casual, curious conversations. That requires being allowed to be wrong, to think out loud, to shoot the shit, to exchange. Imposing some sort of correctness requirement, besides being impossible (how on earth would we enforce such a thing without a truth meter?), would kill conversation and therefore kill the forum.

You guys are overgeneralizing based on seeing comments you dislike. I understand (believe me I understand) how frustrating that is, but there are just as many people who agree with you, probably more. The fact that there's a range of views here is normal, inevitable, and fine.

HN has always operated on the principle that readers are smart enough to make up their own minds, i.e. to find their way through internet bullshit however they choose to do so. I don't see any reason to change that operating principle.

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

#404
There's two separate medical systems, one focused on making money and boosting financials where science does not matter, and the other focused on medical science where at least theoretically the financials do no not matter.

Its up to the end user to figure out which system they're interfacing with and act accordingly. Hint, antidepressants make a lot of money for the correct people... People who make treatment decisions based on financials and kickbacks are not going to care about all this "science" and "logic" and "statistics" stuff where their wallet is concerned.

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

#405
post #62

Earlier quoted context omitted.

Hence the first S and the I in SSRI. A filter in certain areas increases other areas. Doesn't change overall values.

The S for Selective actually means it only works on serotonin, compared with say, an SNRI, which works on both serotonin and norepinephrine. Impacting the overall values is in fact pretty much the only thing it does.

SRIs are a separate class of drugs: https://en.m.wikipedia.org/wiki/Serotonin_reuptake_inhibitor

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

#406

> 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…

I don't think that's an accurate summary of the state of the art on ECT:

https://www.nice.org.uk/guidance/ng222/chapter/Recommendatio...

It sometimes works, it's contraindicated for certain people, comes near the end of the list of things to try (wait to see if you get better and get some excercise/sleep/sunlight being low risk interventions for mild depression) and even when it is used and does work, starting/continuing antidepressants and other treatments is recommended.

It's just one more tool in an incomplete and inconsistent toolbox, not 1 weird trick your pharma company hates.

I know of one person who recently had some success with it, but they tried other things first.

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

#407

Earlier quoted context omitted.

Hence the first S and the I in SSRI. A filter in certain areas increases other areas. Doesn't change overall values.

I'm not sure what you're suggesting, but SSRIs definitely do change a number of measurable metrics of the serotonin system by prolonging the duration of serotonin in the extrasynaptic space. This is well studied. The first "S" is for selective, meaning they have minimal affinities beyond the serotonin transporter.

I don't think we're disagreeing. Increasing duration spent in one place doesn't change the total count of the molecule. SSRIs don't make the body produce more. That's okay, they work by other means.

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

#408

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.

Well, placebos work fairly well for depression. And it's not like doctors can prescribe them...

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

#409
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

This is very interesting - is that just a general acupressure spikey ball? I am looking for one on Amazon, if you had the link?

Also, reading up on the vagus how is the vagus stimulated via the foot? Reading on wikipedia on the vagus nerve I cannot see how it is connected to the foot in any way?

Thanks in advance

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

#410
post #386

Earlier quoted context omitted.

You shouldn't talk about drugs you have zero experience with either as a doctor or as a patient. SSRIs do work.

Only for severe depression, if you take into account all clinical trials - including the ones buried by pharma companies. This is the work by Irving Kirsch being referenced here, and it's excellent.

Spraying water on your house usually doesn't accomplish very much unless your house is on fire. But if your house really is on fire, it is likely the only thing that works.
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