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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

#381

Post by kokey »

openplatypus wrote: post #344
fragcula wrote: post #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 "eviden…

IMO key quote the study you referenced: > In conclusion, the anti-anxiety properties of SSRIs appear to be largely dependent on expectancy effects on dopamine signaling while SERT blockade is not sufficient for symptom remission. Drug works, if you believe it does :)

I wouldn't be surprised about this when it comes to panic disorder. Just knowing you have some emergency fast acting anti anxiety medication nearby, just in case you need it, can reduce the number of panic attacks. There's probably all kinds of psychological feedback loops when people have anxiety about anxiety and then it escalates because they're anxious about it escalating. I am guessing that medication can help mitigate some components of that feedback loop for some people.

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

#383

Post by kayodelycaon »

ggm wrote: post #76
asveikau wrote: post #67

Earlier quoted context omitted.

> It doesn't make sense to make blanket statements about "the drugs" when psychiatric drugs differ widely in this regard. > I'd be cautious of taking advice from anyone who makes blanket statements about "the drugs". This is bordering on uninformed anti-psychiatry. Yeah, as someone who has been close to people who need antipsychotics, I sometimes feel the anti-antidepressant crowd extrapolates to all psychiatric drug…

I am not anti-antidepressant, or drugs in general. Bipolar people get huge benefit from their medications. And their families! The ones I know also say there are times they miss the emotional highs. It's probably why they (and schizophrenics) go non-compliant.

Antipsychotics are nasty medications. Here are the list of problems I’ve had:

- Sedation (too tired to function)

- Emotional numbness if I need to increase the dose to stop an episode.

- Headache

- Loss of balance.

- Impaired fine motor control.

- My arms and legs don’t move properly. I’ll command my arm to move, and it only moves halfway. I used to fall a lot before I learned to be very careful walking.

- Inability to orgasm.

These get pretty bad in the first four hours after taking them. During the day, if I get dehydrated or have low blood sugar, I can easily get incapacitated and be unable to drive.

And no, my dosage isn’t too high. This is the lowest effective dose I can be on. The alternative is lithium, which can be worse.

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

#384

Post by DFHippie »

pineaux wrote: post #355
fragcula wrote: post #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 "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.

> It was only because Nixon didn't like the fact that kids were not going to war, that the war on drugs was started.

Was it this or that he saw asserting dominance over youth culture as a political winner? Judging from the present moment, bullying the less powerful seems to have a lot of political juice. People want to keep the uppities down.

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

#385

Post by woevdbz »

pineaux wrote: post #355
fragcula wrote: post #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 "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.

I'm not sure we know about the side effects very well yet though?

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

#386

Post by epups »

skjoldr wrote: post #368
marincounty wrote: post #269

Earlier quoted context omitted.

I'm pretty sure I'm hell banned, but forget about all the chemicals of the brain. Read anything by Irving Kirsch. He used The Freedom of Information Act to study All the antidepressants studies that were sent to the FDA by the pill pushers, Not just the cherry picked studies, but All. He found they basically don't work better than Placebo. Personally, I think the "Happy" drugs have been the biggest con job the Americ…

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.

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

#387

Post by davidy123 »

openplatypus wrote: post #344
fragcula wrote: post #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 "eviden…

IMO key quote the study you referenced: > In conclusion, the anti-anxiety properties of SSRIs appear to be largely dependent on expectancy effects on dopamine signaling while SERT blockade is not sufficient for symptom remission. Drug works, if you believe it does :)

The drug does something. It at least creates a distraction. That distraction can create a helpful feedback loop. After all, depressive/anxious/etc thoughts are generally arbitrary (though relentness), out of the all the thoughts one could have. So a chemical causing an effect, or just the process of trying an intervention can be useful. Distraction is incredibly important in therapy, it is after all ultimately how we all deal with the fact our lives have an end.

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

#388

Post by jinder »

jinder wrote: 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…

To add to my comment, this explains why SSRIs take some time to work - it's the signalling through the vagus nerve that takes time to impact the brain. Other compounds such as curcumin and famotidine (H2 antihsitamine) have also been found to work via this mechanism. For many many years scientists had dismissed curcumin as having no effect because it's not bioavailable - recent research has shown that it doesn't need to be if it directly activates your nervous system! There's a lot more research that needs to be done here, and I think promising therapeutics for impacting brain function are coming our way as researchers learn more.

If you consider the brain a state machine, inputs from the nerves - through gut-brain axis, through your eyes and ears (socialising, environmental cues, sounds of safety vs sounds of threat), through your skin (touch) etc all impact the state. This state can range from safety to fight-or-flight (anxiety) to shutdown (depression). This is hugely simplified (for example neuroinflammation, endotoxins/LPS etc can impact this also) but I've found it very useful for regulating my own state and understanding why I feel happy, agitated, low etc.

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

#389

Post by autoexec »

asdff wrote: post #114
walrus01 wrote: post #19

I have a completely unscientific, subjective theory that some significant portion of depression in the population as a whole is caused by the economic circumstances that some people live in. Things like being trapped in a dead end job to keep healthcare benefits in the USA, living in a never ending treadmill of debt.

You don't even have to be broke to be trapped in the stranglehold of modern society and feel like shit about it. Just because you are paid well doesn't mean the work you are doing is remotely engaging or interesting or doesn't want to make you hate yourself. Being rich doesn't insulate you from toxic coworkers, in fact probably the higher you end up marching up the economic ladder the more of these narcissistic and t…

> How many billions of calories have been burned to fuel thoughts of worry about an outfit choice around the world?...The stress society tries to shovel on you is such a waste of energy and does nothing to help you.

Sadly, not enough to offset our sedentary lifestyle and diets. I can't be too concerned about the energy expenditure involved in worrying about meaningless things. For now anyway, we've got energy to spare. The toll of all that stress on our bodies is much worse than the calories we lose. Still, I'd rather be worried about the trivial things that we occupy ourselves with than the life or death worries humans regularly faced when we were berry foragers. Going from worrying over "Will we eat today?" to "Which of several restaurants should we go to for lunch?" is a blessing.

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

#390

Post by jinder »

cameronh90 wrote: post #347
locusofself wrote: post #45

Anecdata, but I was often depressed for most of my adjust life. Around 5-6 years ago (age 33 at the time), I started taking 20mg Citalopram. I have experienced almost no depression since I started taking this medication, I'm far more focused and productive than I have ever been. It could be a factor of age and getting married as well, and just settling into my life. But my depression felt like something out of my con…

Sertraline has almost entirely fixed my panic disorder. It had no obvious cause and months of therapy had no impact. Within a few days of taking sertraline, it was essentially cured. I still get anxious from time to time but I'm able to live a completely normal life again. I had a few side effects (GI especially) for a few weeks but now the only side effect I have is I yawn a lot more, which is pretty tame. I'm a big…

You're correct - it appears to work via the gut-brain axis, see my comment above.
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