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Re:The serotonin theory of depression: a systematic review o... by jdietrich on Friday February 28, 2025 @05:51PM (#43212806)
I read this sort of critique often, but what are people living with debilitating depression supposed to do? SSRIs are barely better than placebo, but so is psychotherapy; SSRIs have side-effects, but at least they're cheap and readily available. Exercise is also barely better than placebo, if you're actually capable of maintaining that effort. Everything else in the armamentarium is some combination of less effective, more risky and/or prohibitively expensive.

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?

Re:The serotonin theory of depression: a systematic review o... by kypro on Friday February 28, 2025 @06:36PM (#43213328)
> I read this sort of critique often, but what are people living with debilitating depression supposed to do?

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.

Re:The serotonin theory of depression: a systematic review o... by cbsmith on Friday February 28, 2025 @07:49PM (#43214181)
> 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.

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.

Re:The serotonin theory of depression: a systematic review o... by carabiner on Friday February 28, 2025 @09:32PM (#43215026)
> I read this sort of critique often, but what are people living with debilitating depression supposed to do?

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.

Re:The serotonin theory of depression: a systematic review o... by DANmode on Friday February 28, 2025 @11:05PM (#43215746)
> what are people living with debilitating depression supposed to do?

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.

Re:The serotonin theory of depression: a systematic review o... by tsimionescu on Saturday March 01, 2025 @12:01PM (#43221237)
> Way more depression than anyone is aware is clinical depression.

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"?

Re:The serotonin theory of depression: a systematic review o... by s__s on Saturday March 01, 2025 @02:44PM (#43222901)
Clinical depression is neither of those things.

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.

Re:The serotonin theory of depression: a systematic review o... by DANmode on Sunday March 02, 2025 @12:02AM (#43227530)
Turns out I was using the term completely wrong, and meant "secondary depression".

Thanks.

Re:The serotonin theory of depression: a systematic review o... by tsimionescu on Sunday March 02, 2025 @04:10AM (#43228709)
No problem, I suspected you meant something like that, but also didn't know this term.

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.

Re:The serotonin theory of depression: a systematic review o... by Modified3019 on Saturday March 01, 2025 @06:02AM (#43218106)
For me, I found Bupropion slightly effective, and Dextroamphetamine very effective for my depression.

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.

Re:The serotonin theory of depression: a systematic review o... by partomniscient on Saturday March 01, 2025 @07:22AM (#43218555)
Thanks for your personal empircal revelations.

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.

Re:The serotonin theory of depression: a systematic review o... by caycep on Saturday March 01, 2025 @11:45AM (#43221060)
bupropion does...a lot of things (including mildly doing what dextroamphetamine does...). A lot of these drugs don't just hit one receptor type...(don't get a pharmd started on receptor affinity binding profiles...)
Re:The serotonin theory of depression: a systematic review o... by partomniscient on Saturday March 01, 2025 @01:13PM (#43221898)
Fair call. So much of this stuff is simplified for us laypeople, but yeah - when you look up what so-and-so molecule does and find out how many different binding sites it interacts with as an agonist/antagonist/catlyst (and sometimes they've only measured interactions in rats) you realise there's a heck of a lot of stuff going on.

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.

Re:The serotonin theory of depression: a systematic review o... by mewpmewp2 on Sunday March 02, 2025 @07:43AM (#43229927)
Yeah, we have all these nice labels for all sorts of things, which makes it sound like everything is figured out, but this is definitely very far from the truth and complexity.
Re:The serotonin theory of depression: a systematic review o... by HalfCrimp on Saturday March 01, 2025 @06:30PM (#43225205)
I had similar insomnia issues with bupropion (which was otherwise greatly superior to SSRIs for me) until I started taking it immediately before going to sleep. I slept slightly shorter than usual, but woke up feeling great and had no issues getting to sleep.
Re:The serotonin theory of depression: a systematic review o... by arcticbull on Saturday March 01, 2025 @06:57PM (#43225489)
Bupropion is a noradrenaline and dopamine reuptake inhibitor, and a nicotinic receptor antagonist. You issues with sleep or probably due to the noradrenergic effect.
Re:The serotonin theory of depression: a systematic review o... by catlifeonmars on Saturday March 01, 2025 @12:51PM (#43221670)
> 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.

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.

Re:The serotonin theory of depression: a systematic review o... by Natsu on Saturday March 01, 2025 @06:28PM (#43225185)
> what are people living with debilitating depression supposed to do?

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.

Re:The serotonin theory of depression: a systematic review o... by ada1981 on Sunday March 02, 2025 @01:08AM (#43227865)
1. Seek to heal the underlying trauma / inflammation. Transpersonal work, psychedelics, somatic therapy.

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.

Re:The serotonin theory of depression: a systematic review o... by mewpmewp2 on Sunday March 02, 2025 @07:41AM (#43229911)
These things definitely help, but the question is how do you get someone started with all of it. It all seems pointless to do for someone with depression.
Re:The serotonin theory of depression: a systematic review o... by mathgladiator on Tuesday March 04, 2025 @12:22PM (#43257543)
They need friends willing to drag them kicking and screaming.
Re:The serotonin theory of depression: a systematic review o... by ada1981 on Tuesday March 04, 2025 @09:25PM (#43261872)
Yes. Part of the issue is that it's self reinforcing. Once you show this sort of list and accompanying research to someone with depression, it then becomes a choice to stay depressed.

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".

Re:The serotonin theory of depression: a systematic review o... by agensaequivocum on Wednesday March 05, 2025 @03:50PM (#43272182)
Re:The serotonin theory of depression: a systematic review o... by ada1981 on Thursday March 13, 2025 @05:33PM (#43357431)
Great thread. Yes, it’s possible.
Re:The serotonin theory of depression: a systematic review o... by agensaequivocum on Tuesday March 04, 2025 @10:06PM (#43262146)
Lots of morning, midday, and evening sun on as much skin as possible. Lot's of supplemental inositol