How Antidepressants Work, at Last?

I think I have both, and it’s often hard to tell them apart.

>If the world is actually bad, then that's not a malfunction

In either case the treatment is the same. Doctors and psychiatrists are powerless to do anything to actually put their patients in safe and wholesome environments.

Not necessarily. You can split a definition in many different ways depending on what you're trying to explore, but one way of differentiating types of depression is exogenous vs endogenous. Exogenous depression is a reasonable reaction to bad circumstances - a close family member dying - whereas endogenous depression is internally generated and not related to any circumstances. There are many different ways of talking about "depression", many of them talking about different things - one of the difficulties with psychological terminology is that often that it's just descriptive of someone's behaviour rather than underlying causes, because it's such a complex area.

Not sure about hoarding specifically, but depression can definitely cause similar outcomes. It usually causes a lack of motivation, resulting in many consequences ranging from procrastination up to neglect of personal hygiene and of course keeping things tidy. Pair this with a potential shopping addiction or something in that vein and the differences start to blur.

Like mainly sleep “aids”, DPH just puts you into a fatigued state that is unlike naturalistic sleep. If insomnia / rumination / etc would otherwise keep one up and the diphenhydramine allows one to fall asleep and get a night of suboptimal sleep as opposed to no sleep, it’s of course worth it, but otherwise stay well away.

Interestingly almost everything that induces sleep harms the actual sleep quality. However I remember reading that GHB appears to improve sleep architecture, although I’ve never tried it personally

Out of curiosity, do you feel antidepressive qualities from other dopaminergic substances? (Part of modafinil's mechanism of action is thought to be dopaminergic.) Also, do you feel like you might have ADHD?

Just asking this out of curiosity, because I'm also someone who consistently experiences antidepressive effects from modafinil. Though for me it's typically more of a feeling that lasts for about 1 - 4 hours after use rather than a steady, stable mood lifting effect.

I have Medicare now after a 9 year battle.

Obvious fallacy here: we are all descendants of those humans who survived - at least until having children. Those who offed themselves early are selected out of the genepool.

Note the above is not to suggest that there’s not a number of factors of a modern environment that we’re not properly/perfectly adapted for. But the handwavy “people weren’t depressed and anxious in the old days” is an illusion.

Hi, how did you find out you were allergic to half the food you were eating? I would like to know more about tests/elimination diets you have tried.

There's a quotation from Abraham Maslow that I really like, which I think is similar to your point.

> I am deliberately rejecting our present easy distinction between sickness and health, at least as far as surface symptoms are concerned. Does sickness mean having symptoms? I maintain now that sickness might consist of not having symptoms when you should. Does health mean being symptom-free? I deny it. Which of the Nazis at Auschwitz or Dachau were healthy? Those with a stricken conscience or those with a nice, clear, happy conscience? Was it possible for a profoundly human person not to feel conflict, suffering, depression, rage, etc.? In a word if you tell me you have a personality problem, I am not certain until I know you better whether to say "Good" or "I'm sorry". It depends on the reasons. And these, it seems, may be bad reasons, or they may be good reasons.

https://en.wikiquote.org/wiki/Abraham_Maslow

That I never understood. US is an extremely rich country. Of course there are poor people, but there are lots of not poor people. In my country we don't have money if one does not work. He'll die from starvation. Well, probably some friends will help him not to die, but you got the idea. If you don't have a house, you don't really have any recourse, you have to live in basements under buildings and you'll eventually die as usual temperatures at winter are around -20 Celsius degrees. You can be beaten to death by some crazy person (well, at least you can't be shot, as guns are prohibited). People drive like crazy, so you can be killed by a car accident. If something unjust happens, you can't really rely on police, it might be corrupt and it happens in everyday life. If you need something from government, you might need to bribe the officials and I'm talking about ordinary person needs, not some enterprise stuff. I don't think that there are many grown-up people who did not bribe officials in their life.

Life is miserable here. And people don't run to hang themselves. They are trying to find happy moments and relish in those moments.

It's absolutely normal for a man to live in misery. Our humanity lived in misery for thousands of years and billions of people are living in misery right now. Our brain should be adapted to it by now.

Depression is maladaptive. My environment was shitty and that’s part of how I developed depression, but depression didn’t make surviving that easier. It made it far, far worse. There were also good things in my life; but I couldn’t experience pleasure from those good things because of the depression. Even after I got out of that environment I couldn’t enjoy life.

Meds were a godsend. They allowed me to escape from depression long enough to deal with depression. Could I have done so even while still in a shitty environment? Probably, because the key ingredients for me were: meds, learning to identify good things, and not burying my feelings.

That’s not to say we shouldn’t be solving all these problems, but in the meantime let’s not tear down things that work for people because they don’t directly address a more intractable root cause.

Well said.

I’ve used ADs as a “band-aid”: something for three months or so at a time when necessary, to stop me a) killing myself [though thankfully it’s been a long long time since I had those intrusive thoughts] and b) giving me just enough “normality” to go and make whatever changes I can that pushed me in the direction of an episode or made an extant one worse, and lastly c) give me enough motivation that I can work properly with my psychologist/psychotherapist.

I’ve had very good “reasons” for my crippling depression, but usually I can’t see the forest for the trees to work out what it is while deep inside the episode.

Luckily for me, citalopram works with basically no side effects when taken for a couple of months. I’m glad that’s the case, but I’ve seen so many of my friends get no relief from ADs at all, along with so many (sometimes life altering!) side effects, that it makes me sad at times.

Lastly, buprenorphine is remarkable for me in terms of its anti depressive effect. Once monthly Buvidal injection not only solves my past issues with drug abuse, but neatly solves my depression. Fascinating stuff.

Talk about arbitrary, on the pharmaceutical front some very revealing and somewhat forgotten info seems to be in the comments:

>anon the II says: 19 February, 2021 at 1:03 pm

>About 27 years ago, a little company that I worked for was going through another transmutation in order to survive. We became a high-throughput screening/combinatorial chemistry company. The CEO told a story about how, by the time anyone figured out that we didn’t know what we were doing, we might actually figure out what we were doing. I volunteered to be the technical lead on the combi-chem side. Anyhow, we managed to get bought by Lilly in 1994 and shortly afterwards, we got a visit from Bryan Malloy (https://en.wikipedia.org/wiki/Bryan_Molloy), the inventor of Prozac, who came down to see what his company had purchased. I met with Bryan and we had a lovely chat. But, he let me know that he thought that what we were doing was no better than “pissing in the wind”.

>I guess this means that he was doing much the same.

They did this one weird trick! Doctors hate them!

I'm sure they'll tell us for just one easy payment.

Which is to say, it's probably just a simple lie - either one they are telling us, or one that has been told to them.

If history is any guide it involved an ice pick.

I made my first account just to respond since no one else has.

Think back to something that made you angry, that annoyed or frustrated you. Think back to a time where you got really riled up. A time where you were really pissed off at someone.

You're going to close your eyes for 20 seconds and think about it, feel it, really try to go back to that day and immerse yourself in that moment. Now, close your eyes.

Did you notice anything? Did anything in your body change in the last 20 seconds?

By thought alone, you can change your physiology, your mental state, your blood pressure and heart rate. Nothing in your environment changed, you're still sitting here reading this, yet to your brain you were momentarily somewhere else. For me, stuck in traffic and some wanker just cut me off, nearly caused an accident and seemed oblivious to it all. I wanted to crash my car into his just to teach him a lesson. It can make your blood boil just thinking back to past events where you were wronged.

I had you think back to something that made you angry, and you probably felt that same way you did that day but to a slightly lesser degree. If you continue to think about it, think about how wrong it was, you can feel EVEN MORE ANGRY. But you don't have to.

You can think back to these moments in your life and feel less or more of the emotion by altering the memory, or your perception of the event.

Your past influences who you are. Your past only exists as memories within your mind. Memories can be recalled and changed by your mind.

You can think back to past events and change the way you perceive them. That's the practice of NLP from my perspective. Changing your memories so that they benefit you.

All those times you've been embarrassed, angry, frustrated or annoyed, you can look back at these moments and laugh at them. Think about some negative moment in your life and then literally laugh out loud about how absurd it was.

Seeing a memory in your minds eye you can turn the colour down so it's only in greyscale. You can mute the person saying hurtful things, or change their voice to that of a cartoon character, something absurd and comical. While you're doing all this, recalling past events and memory manipulation, you're comparing your emotions and how your body is responding, before and after each change.

This might be something you can learn how to do in one session, but for me it took lots of purposeful practice. Like a muscle you develop, you become better at this over time.

I don't know. I was in a deep trance. Subjectively, I went up on stage (it was a demonstration at a seminar) sat down in a chair, closed my eyes, and the last thing I remember is Dr. Bandler saying something like "Oh I love it when they fight me..." and then a few moments of darkness and indescribable subjective somethings, then I opened my eyes. Later on people who were watching told me I was up there for about ten minutes.

Since then, except for one (terrifying) three-day period, I've been free from the depression that was ruining my life.

So yeah, like I say, I don't know what he did. (Frankly, in a sense, I don't care. I'm cured! I have a life!) I actually lost interest in NLP after that. I only promote it because it feels irresponsible not to, so many people are suffering needlessly and many of the solutions to their problems are right there if only they knew.

The things that work should get more attention from the mainstream psychologists IMO. (It's been nearly fifty years since we have had a cure for phobias. At some point it stops being funny and starts being tragic. Everyone today who has a phobia is suffering needlessly.)

As for the "theory that someone just made up." That sounds weird to me, because my experience has been that theory is treated as no more than a prop to support hypnosis. The emphasis is always on the pragmatic and empirical. If you go read the books like "TRANCE-Formations" they are really upfront that they have no idea why this stuff works.

Whatever NLP is, they collected "a bunch of things that do work" many of which no one ever noticed and wrote down before, eh?

Basically, you have to go to specialty food stores (the arabian ones are really awesome from my experience) to actually find yogurt that's deserving of the name. For some reason the yogurt sold in regular supermarkets in the US is 'low fat' and 'strange consistency'.

Almost every yogurt is full of added sugar. Sometimes the ingredients pretend it isn't sugar by calling it "evaporated cane juice".

You can get actual healthy yogurt with plain Greek yogurt or skyr, though, it's not hard anymore.

In the article they discuss that known SSRIs weakly bind a different receptor which may be why they have an antidepressant effect. It would explain why more specific SSRIs that are thought to target serotonin receptors selectively do not work. That they see a bunch of them doing the same thing is pretty convincing.

to quote: "Now to the BDNF hypothesis. I used the phrase “unknown mechanism” above, and that’s exactly what this work may have cleared up. The authors show that when the TrkB protein forms a dimer in the cell membrane, a binding site for small molecules is formed at the interface. A whole list of known antidepressants (fluoxetine, imipramine, venlafaxine, moclobemide, ketamine, esketamine, and R,R-hydroxynorketamine) bind to this site at about 1 micromolar levels (and can displace each other in binding assays(, while a set of control CNS compounds like chlorpromazine, diphenhydramine, and indeed S,S-hydroxynorketamine do not. It will not be lost on those who’ve done research in the field that the antidepressant compounds listed above have been thought to work through completely different mechanisms. "

A behavioral component manifests itself as a chemical process within the brain. So it may be used to explain the cause of certain chemical processes, but it's still the chemical processes that have to be dealt with. Though it doesn't necessarily follow that a chemical intervention is necessary: If the cause of the chemical change was behavioral, the solution might be as well, such in the form of various type of therapy.

If that theory is definitely wrong, it hasn't yet worked its way out of common use. Examples:

NHS current website "This type of medication [SSRIs] works by increasing the level of a chemical called serotonin in your brain." https://www.nhs.uk/conditions/generalised-anxiety-disorder/t...

Wikipedia "It is believed to work by blocking the re-uptake of the chemical serotonin by neurons in the brain." https://en.wikipedia.org/wiki/Paroxetine

etc.

After a long battle with depression, this is how I interpret the phenomenon that "boosting" serotonin levels does not work.

SSRI's do not increase the pool of available serotonin, they just artificially increase the amount that remains in the synaptic cleft, facilitating additional firing of the neuron (or for a longer duration, I'm not sure which). They do not increase a neuron's ability to synthesize serotonin and release it into the synaptic cleft at the appropriate time. SSRI's cause our neurons to reuse serotonin longer than they normally would, which is not how we evolved to use serotonin.

The way this felt to me as a human interacting with the world around me was artificial happiness and artificial feelings of ease. I felt "better", but it didn't feel like it was grounded in anything real. I felt happy when happy things happened, but I also felt happy when sad things happened. Eventually it wore off and SSRI's no longer had any effect on me.

I eventually tried tryptophan and B vitamins (specifically B6), which our bodies use to synthesize serotonin. I got a similar effect to when I first started SSRI's, but it felt real. I was able to be happy when something happy happened. But when something sad happened I also felt sad. This effect has endured for 4 years now.

I have since found that I had a serious problem with a particular toxin which poisons many of the pathways involved with serotonin synthesis (among many many others including one of the most fundamental, the Citrate Cycle). A way around the poisoning is large doses of the appropriate nutrients. This is because the toxicity causes serious inefficiencies in their use by the body's biochemical pathways.

This was my personal experience. Depression is caused by many factors and I'm sure what works for me would not work for many. It can be genetic issues, other kinds of toxins, and overwhelming amount of trauma, chronic infections, unhealthy relationships, etc. Or a combination of those.

Where do you see SNRI lowers serotonin?

It's a re-uptake inhibitor for both serotonin and norepinephrine which keeps your body from flushing our those chemicals which raises serotonin levels as long as production is stable.

High doses of SNRI will contribute to Serotonin syndrome, which makes your argument hard to believe.

> "Low serotonin" was never the actual medical position on why antidepressants worked, it was marketing. The medical position is "we don't know why they work"; some antidepressants actually lower serotonin (SNRI) and some increase it (SSRI) and they both seem to help.

This just isn't the case. Maybe the more accurate thing to say is that there have been a few "medical positions" on this issue in the past six to eight decades, and "low serotonin" as well as "we don't know how they work" were both out there in the ether. But even that's not fully accurate, because you'd have to be pretty bold to argue that there wasn't a dominant "medical position" on the matter since biological psychiatry finished supplanting the Freudians for control of the field in the 1970s. The dominant position was the chemical imbalance theory, of which "low serotonin" was one of several variations trotted out over the years to both the public and the medical community.

Psychiatry is one of the medical specialties most profoundly co-opted by pharmaceutical industry interests, and both research and clinical practice have been rife with the effects of this influence. You don't even have to appeal to systematic analyses of how profoundly poor the quality of psychiatric research is, or how much pharma ghostwrites those studies, or anything of the kind. You can just ask a researcher in cancer or in neurology; they'll happily tell you.

To cleave the "medical position" from "marketing", as in your comment, elides what really happened: marketing decided what the medical position would be, and both doctors and the public mostly bought it.

More than I want to die, I want not to be a part of the omnicidal stupidity that seems to define humanity.

I really do want not to die, and I see a viable path forward with that as a result.

An illegal and seasonal path.

I last took a dose in July, and those malignant fucking thoughts are returning.

And nurses keep telling me that psilocybin clearly has not worked (all the while advocating a pill a day, pill a day, pill a day).

If you see a drowning man take a gasp of air, and the keep right on drowning that does not mean that the air did not work.

The system is fucked - but try not to let it eat you.

I live in New Zealand - I can't afford land.

The only possibility for getting around the seasonalilty is growing indoors - and I really don't have the space for that.

Depression for me has caused me to spiral down - so far down that there's no apparent path back up.

I've been down and out for so long that even finding work is damned near impossible - so I can never even get to the point where renting my own place is feasible.

Yet, eating bacon and cha siu makes me happy...

Saturated fat does.

My amateur guess is that because some of these drugs are associated with weight gain and some are not that this mechanism of action is not the primary actor for antidepressants with weight gain side effects.

I did not, because I thought enough others had done so already. Asking other people to do your thinking for you is noise, and belongs at the bottom of the thread. It's fine if you can't be bothered to read it right away: HN has a save feature just for that. But don't inflict your laziness on the commons, especially for an article that is so very short.