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

bmj.com

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

#611

Post by nth_order »

lighttower wrote: post #595
nth_order wrote: post #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 d…

Can you point us to a source for the accepted real physiological effects of ADs that you shared above?

Sure - I should have given some sources in my original comment. The order of my list of purported mechanisms is also not really ordered by significance. I think generally, more and more mechanisms of AD efficacy are discovered, and it can seem that the more we know, the less we know. Additionally of course, there are like 15 different classes of ADs, with hundreds of different compounds in total. What we know for sure I think is that the serotonin and also the monoamine hypotheses of depression are highly oversimplified and even internally contradictory, and many more targets and way more general biochemical mechanisms in the brain must be involved in depression.

But anyways, here are some pointers:

- Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931/)

- Wikipedia: Biology of Depression (https://en.wikipedia.org/wiki/Biology_of_depression#Monoamin...) has some good sources

- One source covering the 5-HT1A autoreceptor downregulation part in particular there is "Serotonin autoreceptor function and antidepressant drug action" (https://pubmed.ncbi.nlm.nih.gov/10890313/)

- This is also covered in "Mechanisms underlying the speed of onset of antidepressant response": https://link.springer.com/chapter/10.1007/978-3-0348-8344-3_...

- I personally like the books "Antidepressants" by Leonard (that the previous paper is a chapter of) and "Anxiolytics" by Briley and Nutt. These discuss really a wealth of observed/purported mechanisms, also for example including the significance of late gene products.

- Wikipedia: Pharmacology of antidepressants (https://en.wikipedia.org/wiki/Pharmacology_of_antidepressant...) has great sources, especially on the anti-inflammatory and immunomodulative pathways, and introducing HPA axis modulation as another possible pathway.

- Here's something about the significance of common ADs being FIASMAs: https://www.semanticscholar.org/paper/High-activity-of-acid-... - also check out the related articles below for more interesting material.

- ADs and neuroplasticity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/

- ADs and neurogenesis (this is not clear-cut in its clinical significance, and many ordinary things like exercise can promote neurogenesis): https://www.sciencedirect.com/science/article/abs/pii/S01637... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155214/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230505/

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

#612

Post by nth_order »

root_axis wrote: post #518
kemiller wrote: post #478

Earlier quoted context omitted.

I think ADHD causes depression because you get constant negative feedback from (many) teachers & bosses.

IMO, this hypothesis doesn't pass the smell test. One of the defining qualities of clinical depression is that personal success in life does not obviate the symptoms; there are many widely know examples of beloved and successful people being unable to overcome the burden of crushing depression.

Another complicating factor is that it is assumed that there are a few different subtypes of depression. For example with and without psychotic features. Another subtypes is the "atypical depression", which actually has, in contrast to classical major depression, "reactive mood" and a high degree of "rejection sensisitivity": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990566/

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

#613

Post by ssvss »

y-c-o-m-b wrote: post #473
roody15 wrote: post #459

Think we have known this for a while. For example Wellbutrin (Bupropion) works well for many people and it doesn’t work on serotonin levels at all. In fact it causes an increase of dopamine uptake in the brain. Think increasing the dopamine levels causes a variety of changes to complex systems in the brain that are not really fully understood. SSRi’s also cause changes to underlying systems in the brain that are not…

I'm on Wellbutrin (lowest dose) and it works great. I have no side effects whatsoever. Been on it since 2019. It's kept my depression in check and even helps with my ADHD a little. They say you can't drink alcohol with it, but I binge drink every weekend (I really love alcohol) with no problems. SSRIs were an absolute train-wreck to be on; they made me angry and violent. I was on them for 10 years and I honestly don'…

How long did it take for Wellbutrin to work for you. I was on it for 2 months, it didn`t help, so I stopped.

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

#614

Post by daniel-cussen »

daniel-cussen wrote: post #365
king_magic wrote: post #363

Earlier quoted context omitted.

I have (and have always had) an awesome life. I’ve still struggled with depression.

EDIT: Had and have always had an awesome life? The fuck? Sounds counterfactual. Yeah a perfect life with no problems. Wouldn't the depression make it not awesome? But to narrow down, shrinks dream of some like sweetener or artificial coloring they can add to all the shit the give someone to make it taste good. A spoonful of sugar makes the medicine go down! No it doesn't. It tastes bad because it's poison. That is th…

EDIT to king_magic: man I don't know what your deal is. I bet it's really good on paper. Just not as good in living it out, hence depression.

.

I wish I could press a button on the user interface to talk to someone in person. Real life. You and I. Real Meat. In person. king_magic and daniel-cussen.

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

#615

Post by mandmandam »

hirvi74 wrote: post #600
sizzle wrote: post #569

Earlier quoted context omitted.

There are studies about magnesium supplementation helping with adhd

Star Slate Codex (Scott Alexander) wrote that the evidence for such is basically non-existent. Thus such claims remain dubious at best. Though this was many moons ago, and things change. Do you happen to know of any research that supports this?

SSC also wrote a long article mildly trashing "The Body Keeps The Score" (which is truly excellent and important), with some very poor logic. He's not infallible.

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

#616

Post by y-c-o-m-b »

ssvss wrote: post #613
y-c-o-m-b wrote: post #473

Earlier quoted context omitted.

I'm on Wellbutrin (lowest dose) and it works great. I have no side effects whatsoever. Been on it since 2019. It's kept my depression in check and even helps with my ADHD a little. They say you can't drink alcohol with it, but I binge drink every weekend (I really love alcohol) with no problems. SSRIs were an absolute train-wreck to be on; they made me angry and violent. I was on them for 10 years and I honestly don'…

How long did it take for Wellbutrin to work for you. I was on it for 2 months, it didn`t help, so I stopped.

It only took about a week. It wasn't a massive difference in mood, just a small boost, which is all I needed to get by.

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

#617

Post by ryloric »

hirvi74 wrote: post #484
moth-fuzz wrote: post #463

Earlier quoted context omitted.

I have a friend that's convinced that her ADHD 'causes depression' because her brain does not produce 'enough dopamine'. I'm noticing more and more among my peers a mythology around brain chemicals that's about as accurate as the four humors but with a scientific-sounding veneer. All brain function (and thus all bodily function, because the brain is the whole person /s) can be traced back to the presence or absence o…

> I have a friend that's convinced that her ADHD 'causes depression' because her brain does not produce 'enough dopamine' Interesting, and she is somewhat right, but is wrong about the 'enough dopamine' part, if I understand correctly. I have heard that dopamine plays a role in ADHD (seems likely our neurotransmitters don't absorb enough, but even that is an overly simplistic explanation of the unknown and true reali…

I go through this process regularly when I have to put away groceries. I get progressively anxious about just leaving them on the counter, and it devolves into me ignoring them until I have to use them, by which time some of them are no longer usable.

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

#618

Post by ffwacom »

y-c-o-m-b wrote: post #473
roody15 wrote: post #459

Think we have known this for a while. For example Wellbutrin (Bupropion) works well for many people and it doesn’t work on serotonin levels at all. In fact it causes an increase of dopamine uptake in the brain. Think increasing the dopamine levels causes a variety of changes to complex systems in the brain that are not really fully understood. SSRi’s also cause changes to underlying systems in the brain that are not…

I'm on Wellbutrin (lowest dose) and it works great. I have no side effects whatsoever. Been on it since 2019. It's kept my depression in check and even helps with my ADHD a little. They say you can't drink alcohol with it, but I binge drink every weekend (I really love alcohol) with no problems. SSRIs were an absolute train-wreck to be on; they made me angry and violent. I was on them for 10 years and I honestly don'…

>but I binge drink every weekend (I really love alcohol) with no problems

this is almost certainly the cause of your 'depression'

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

#619

Post by eurasiantiger »

moth-fuzz wrote: post #463
nth_order wrote: post #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 d…

I have a friend that's convinced that her ADHD 'causes depression' because her brain does not produce 'enough dopamine'. I'm noticing more and more among my peers a mythology around brain chemicals that's about as accurate as the four humors but with a scientific-sounding veneer. All brain function (and thus all bodily function, because the brain is the whole person /s) can be traced back to the presence or absence o…

It’s more like she has quantitatively or qualitatively different dopamine receptors.

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

#620

Post by pinkhorn »

eyelidlessness wrote: post #127
tuxie_ wrote: post #75

Earlier quoted context omitted.

Don't take it personal. Both things can be true, you can have adhd and adhd can be overdiagnosed, doesn't mean that none of those diagnostics are valid. I'm sure you must be tired of people telling you about how overdiagnosed adhd is, I'm sorry about that, but don't take it personal, it's just a person on the internet.

> Don't take it personal Oh I take it personally. I’m alive today because I sought diagnosis and treatment. I very nearly wasn’t alive from the consequences of being undiagnosed and untreated. I very probably would be dead today if I had taken this “just person on the internet” more seriously than I already had. I’m more than tired of people offering their ignorant opinions about stuff they don’t understand.

I hear you. The ignorance around ADHD is appalling. My medication (Elvanse) works wonders - being able to focus like normal people has entirely changed my life.

I remember the first time I took one of those pills, I was astounded my how clear my mind became. It was like the noise switched off, and I could just get on with what I needed to.

Like you, I was diagnosed as an adult. I have considerable regret for all those years prior wasted without diagnosis and medication. I'm trying to undo all the maladaptive behaviours I've developed likely because of this, and shed myself of the many, many guilts I feel. But it's a long hard slog.

I wish my parents were still alive so I could talk to them about it all, and show them the person I've become since.

When I see confident expressions of ignorance about ADHD, or even worse, scammers and liars trying to take advantage of people with ADHD, it also makes me see red. You're not alone in this. I think you were right to speak out here, whatever anyone else says.

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