The serotonin theory of depression: a systematic review of the evidence (2022)

Do we need better treatments for depression? Yes, desperately. Are some people with mild, self-limiting illness taking SSRIs unnecessarily? Probably, in some places. Are many people with serious depressive illness not trying drugs that might help them? Definitely. Does denigrating the least-worst treatment for most people actually help anyone?

I don't disagree strongly with anything you've said here, but I think as someone more on the other side of this argument – that in most cases people are probably better off not taking SSRIs – that part of the problem is that people don't learn to deal with their depression anymore and as a society we don't care to help those suffering with depression beyond just telling them to take psychoactive drugs.

As a depressed person myself and someone who knows a fair few depressed people, I do believe you can learn to manage it in the vast majority of cases. I think as a society if we tried to help people understand and manage their emotions then perhaps we could help people without medicating them to be honest. It's just that medicating them is easier, as you suggest.

I don't really care what others do though. If people want to medicate then more power to them... All I can say is that in my experience it's the wrong thing to do and that the only long-term way to deal with depression is to learn to experience it without being overwhelmed or burdened by it. In this sense pushing people straight to SSRIs denies them the chance at a more lasting solution. Ideally I think SSRIs should be the last option.

There's some inconsistencies in your logic there. If SSRIs aren't effective, how is it that people "don't learn to deal with their depression" due to SSRIs?

> As a depressed person myself and someone who knows a fair few depressed people, I do believe you can learn to manage it in the vast majority of cases.

The evidence supports that. The evidence also supports that without help, a lot of people won't learn to manage it, and many will literally die because of it.

Not waste money on useless treatments? Seek out other treatments like TMS (SAINT protocol), ECT, ketamine?

I don't know why you suggest that useless treatments are better than nothing. You could also throw in prayer, naturopathy, and seeking a psychic.

Americans hate to hear this: Not all problems have solutions. Really.

Way more depression than anyone is aware is clinical depression.

Address the issues in your life, and your long-tail health.

For me, it was multiple systemic infections - took the drugs and buried it down, didn't realize until it got really bad. Luckily I was young enough to survive the mistake.

If your endocrine system is doing the wrong thing, ask why.

I had severe depression during Covid, manifesting as involuntary and passive suicidal ideation. Basically a hours long whirlpool of daydreaming about dying in some way, because it was the only thing which brought comfort to what I would best describe as a sort of mental agony, but without pain. Just the constant need to escape existing. Passive meaning at no point was I actively intending to act on it, but obviously this was not something to be allowed to continue.

The depression basically severely reduced my ability to mitigate my ADHD symptoms, causing them to become very apparent, essentially being co-morbid with each other. With that context, I first did some non-stimulant preliminary alternatives like:

* Bupropion HCL. This provided partial mitigation of the depression. Basically it was manageable and not threatening to implode my ability to do basic life tasks. No effect on my ADHD.

* And Atomoxetine (Strattera) which within the week had brought back my involuntary hours long daydreams of dying, and really fucked up my dick/physical and mental sexual response, which lingered for a few months after despite quickly ending treatment. As a male, I severely underestimated how much having a healthy sexual response contributes to overall wellbeing.

After that I tried extended release Dextroamphetamine.

The very first day, I wasn’t what I would consider euphoric, but I had a distinct calm sort of sense of wellbeing that was very much in contrast to the previous several months. Basically I could actually start to feel that things could be better, rather than trying to brute force reason while suffering. I liken it to what you feel when the pain from when you stub your toe fades, and you have some minor lingering endorphins.

After that first day, I didn’t feel anything else directly connected to taking the pill after that. I’d typically forget if I already took the pills 2-3 times a week (meaning skip the dose). All I could notice after resuming after skipping a day, was being slightly more chatty, and feeling like I was slightly worse at driving. The few times I probably doubled up, I’d feel this sort of mild head pressure.

But the overall effect of Dextroamphetamine within 3 days was the complete elimination of my passive ideation. Intrusive thoughts are like flies, they land on everyone, but healthy people can brush them away. I still had to take care not to voluntarily sustain negative thoughts, but it was actually voluntary now.

I later moved to Lisdexamfetamine ER because the supply of dex at the time was severely constrained, but it was basically identical. Supposedly less addictive/abusable too, though for me either felt as addictive as a collagen supplement.

After a few months, I had the dose lowered, and several months later, I halted taking stimulants. They didn’t really do much for my ADHD symptoms, and I felt that whatever had triggered my depression had cleared up so I could manually deal with the symptoms like I always have.

So that left some mild side effects of slight head pressure, probably being a slightly worse driver, probably being a slight detriment to my sleep, and possibly increasing jaw clenching (I now have a fitted nightguard), so I had zero reason to continue.

But it’s very reassuring that if I get another severe depression episode for some reason, I now have a first response tool I can use.

I'm sure you know Bupropion doesn't affect seratonin, its a dopamine re-uptake inhibitor.

As someone who also doesn't seem to respond much to seratonin related meds, Burproprion worked somewhat but I suffer from increased insomnia as a side effect. I actually respond better to things mostly affecting GABA and NMDA rather than the 'classic' anti-depressents.

That said I was trialled on methylphenidate and all it did was make me procrastinate waaaay faster, so personally I'm avoiding any stimulants stronger than caffeine.

I don't know what you wanted to say here. Clinical depression is typically used as an explicit emphasis to either emphasise that it is professionally diagnosed (as opposed to layman observations), or to emphasise that it is depression so bad it requires hospitalization (such as people who are so depressed they literally can't get out of bed for days on end).

But you seem to be using this term to mean "depression symptoms caused by other diseases"?

I had this experience as well; in particular it really impacted my ability to work/keep a job. The added stress in turn worsened my depression, etc.

Fortunately, I was able to take almost half a year off and focus on stabilizing/recovering without further damaging my career or economic status. Many people are not so fortunate.

I also got slightly weirded out when I found out something I was taking interacted with the mu-opiod receptors even though it wasn't an opiate.

It’s also called Major depressive disorder. It’s basically depression that isn’t a temporary response to something. It’s long lasting depression that doesn’t go away.

You can easily look up the diagnostic criteria online.

My recommendations having dealt with it would be sunlight, exercise, weight loss and being evaluated for sleep apnea.

I'm sure there are many, many causes of depression, but I've seen a lot of people who are overweight, which causes apnea, which gives them no sleep, which makes them miserable so they feel like they can't do anything (and may thereby gain further weight). Meanwhile lack of oxygen may cause them night terrors because they're literally suffocating in their sleep (and the bad dreams / night terrors may literally relate to this). So they get anxiety when the drowning reflex goes off at bad times and they hyperventilate.

I've seen more good from this than drugs, which may just leave someone sleepy and non-functional all the time, but as always, YMMV and you should talk to your doctor.

Thanks.

2. Get into nature a few hours a week.

3. Write 14 gratitude letters.

4. Dance every day.

5. Be part of a community in which your competence is growing and you have a position of status and mentorship.

6. Tell the truth in your relationships.

7. Align your self with a solar / seasonal calendar.

8. Meaningful work in a healthy work environment

9. Get microbiome sorted out

10. Fast for a week, then reintroduce healthy non inflammatory foods. Have levels checked via blood panel.

—

If someone does all of these things and maintains it for 40+ days; they will feel much better.

Depression is the result of the compounding effects of a series of small, invisible daily choices and can be reversed by small daily choices.

I spent a decade in and out of suicidal depression, and am grateful to have followed an alt path and helped many others to do so.

By the way, a common cause for (usually light) secondary depression that more people should know about is vitamin D deficiency, quite common for even slightly darker skinned-people living in Northern Europe.

You can remind people that are choosing to be depressed, when they choose not to begin doing thing things to build the momentum needed to not be depressed.

They may be angry. This is ok, since anger is a step towards feeling the full range emotion which is needed to heal. Anger can lead to greif which can lead to sadness which can lead to joy and gratitude.

Depression is about repression or supression of feeling, not feeling the "wrong things".

https://threadreaderapp.com/thread/1727013824115396634.html