Well, 4 can also be considered as "just let some time pass", which as a cure can be synonymous with 3, or with 5: a change of fortunes/circumstances (as there is also situational depression, being depressed about actual shitty circumstances, from sickness and close deaths to incarceration).

In any case, those 4 things you've mentioned are well enough already.

I’d follow the results of Cybin and their psilocybin clinical trials.

Sex and love

LSD (not without risks but it changed my life). Maybe that counts as #3 though.

Sleep deprivation

That’s a short term band aid and possibly damaging long term.

Do you have data/studies for either side? Genuinely interested in this, because intuitively it makes sense - sleep deprivation amplifies emotions - but I also have experienced first hand that long term sleep deprivation slowly deteriorates my emotional state.

There’s probably way more going on, but the glymphatic system impairment caused by (proper) sleep deprivation could be one of the big factors. Basically the trash can’t be taken out. Here’s a paper that explores neurological disease as a result of that: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261373/

ECT works on many treatments per patient where the active ingredient may be the same as sleep deprivation:

"Another proposed mechanism of action is that the seizures induced by ECT cause a profound change in sleep architecture (a reversible inhibition of REM sleep); it is this change in the state of the organism that drives the therapeutic effects of ECT and not any simple change in the release of neurotransmitters, neurotrophic factors and/or hormones."

So a small percentage of patients not relapsing after one sleep deprivation would actually make it the best available cure with reduced risks compared to ECT.

Other treatments possibly aren't curative and have not as serious side effects as ECT, more similar to sleep deprivation.

I'm not really interested in giving anyone medical advice, etc, based on my selective reading of pubmed, I just think it is important to list treatment options neutrally and with more consideration of what self treatment patients are probably very effectively applying if managed medical treatment is supposed to have a safer and better outcome.

Some things to take into consideration:

- Optimizing the microbiome. There’s tons of studies around various strains and methodologies etc. You could benefit from just eating no sugar and more fiber, or you could be in need of a fecal matter transplant. Unfortunately the microbiome and its effects on health is still not that well understood.

- Light therapy, or photobiomodulation with near-infrared light has some promising studies. I’ve personally used it to great effect.

- Magnesium supplementation has been shown to work in some treatment-resistant cases (obviously only works if you’re deficient). Mg is quickly eliminated via kidneys, so lower doses spread over the day might work better.

- Check Glycine levels (or just try a supplement, it’s cheap). Low levels are linked to depression. It also improves sleep usually, a nice side effect.

- Anything that lowers inflammation in the brain could work well in treatment resistant depression.

I read an article about gardening being a great source of anti depression. Not only the activity, but also the bacterias in the soil, which we are deprived of in our modern society with it's hygiene and antibiotics. These bacterias lived with us for a very long time (thousands of years) and just recently we started to kill them in us. Additionally there are connections between the gut microbiome and the brain which are not fully explored yet.

I was sitting on a small hill in the grass and was feeling depressed like the weeks and months before that. I figured, a little bit of dirt couldn't hurt. I licked my finger, stuck it in the sand, and ate it.

This is of course anecdotally, but I'm certain it helped me.

I'm very glad you are feeling better, but it's important for others to be aware that this is pseudoscience.

Do you have access to cold water. sea lake, bath with ice? Get in on a regular basis (with necessary precautions)! Access to a sauna? Get in on a regular basis. Engage in regular exercise, cardio is great. Don't feel like it? Do it anyway, treat it like it's meds because in a very real sense it is. Get your diet in order. Sugar is the devil! Get your sleep in order. Try and get to sleep before midnight and when you wake up in the morning go outside (before 9am) and get some morning light in your eyes. It improved my sleeping pattern immensely.

It may not be a dead cert cure for depression but all of the above has accumulative effects over time and it is more difficult to feel bad mentally when you are feeling really good physically.

> Engage in regular exercise, cardio is great. Don't feel like it? Do it anyway, treat it like it's meds because in a very real sense it is.

This is not necessarily good advice, overtraining is a thing and actually causes depressed mood. Check heart rate variability to make sure you are rested enough to exercise.

People with depression should really try to keep inflammation low, and preventing overtraining is an important part of that.

This is like saying an anorexic shouldn’t eat because they might eat unhealthy food.

Everyone should get regular exercise. Worry about overtraining after you’ve started training at all.

Overtraining happens right after you start out, because you're not used to the training at that point. You're suddenly running a _huge_ ATP deficit, and ATP (and other metabolites) can't be produced on a whim, metabolism has to adapt. Many people stop right after they started because they exhausted themselves too quickly, instead of waiting 2 days and continuing then. Everybody should be worried about overtraining. Not only for mental health, but also metabolic and heart health. You know, sudden cardiac arrest and things like that.

I don't disagree at all with doing regular training. I'm doing 10km walks almost every day now. But everybody's metabolic capabilities are different, and rest periods are highly individual. Rest isn't optional, ask any bodybuilder.

Granted overtraining is a thing but undertraining or no training is also a thing. At the level most people are at (sedentary or undertrained) coupled with the fact that people have reasonable intuitions as to when they feel tired or not, the risks of overtraining is signficantly less that the benefits of regular exercise both physically and mentally.

You do mention inflammation in a previous comment and overtraining increases it but does the negative consequence of inflammation due to overtraining on how one feels subjectively outweigh the cascade of endorphins and neurotransmitters in response to exercise that correspond to an uplift in mood or an alleviation of stress? I'm not sure but in the given context (original post) your point is valid but of much less concern probabilistically and physiologically.

I do grant however that that is only my opinion and very much up for debate.

> does the negative consequence of inflammation due to overtraining on how one feels subjectively outweigh the cascade of endorphins and neurotransmitters in response to exercise that correspond to an uplift in mood or an alleviation of stress?

Usually exercise in overtraining doesn’t feel good in the way you are describing it. It creates extra stress and the body won’t be inclined to release endorphins to encourage that behavior.

When lockdown started I built 1 mile / 30 minutes of walk every day into my routine, plus a few minutes' worth of core strength stuff etc twice per day, short enough not to bore me. (I worked out decades ago that I was never going to spend hours a day down the gym!) I think it helps, and it is at the lower end of widely agreed minimum exercise levels for physical health. And I skip it occasionally when I really want to.

None of this is going to be "overtraining" and/or earn me medals.

If you had ME/CFS, you‘d end up in overtraining. Metabolism is highly individual.

Favorite-worthy comment, thanks! I've certainly had success with some of these and would like to add more to my routine. (I've found it that having a stable, healthy daily routine helps a lot by itself. Getting used to actually getting up and making coffee immediately after I wake up has made a surprisingly large difference to my mornings)

Electroconvulsive therapy

Travel / change of environment

Religion/spirituality, which might be 3. But meditation gets you into a place where you just go "I'm unhappy" without the unhappiness actually consuming your life. Religion removes sources of unhappiness - you make peace with your inevitable death, missing a limb, missing a child, being broke, not being smart enough, wanting more, and so on.