4 ms·

As far as I'm aware, it's been known for decades that we don't actually know what causes depression, and that whilst we know that antidepressants work, we don't

As far as I'm aware, it's been known for decades that we don't actually know what causes depression, and that whilst we know that antidepressants work, we don't know why they work.

drooby 4y ago
How certain are we of this? I’ve seen many studies stating that things like Zoloft are actually no better than placebo. But placebo does work.. because it modifies our expectations.
- alecbz 4y ago
  I’m pretty sure other studies do find differences between SSRIs and placebo. I trust Scott Alexander’s take on this: https://slatestarcodex.com/2014/07/07/ssris-much-more-than-you-wanted-to-know/ https://slatestarcodex.com/2014/07/07/ssris-much-more-than-y... but the one-sentence answer definitely seems to be “it’s complicated” One good quote: > some people have decided that antidepressants’ effect size of 0.3 means they are “clinically insignificant”. > (please note that “clinically insignificant” is very different from “statistically insignificant” aka “has a p-value less than 0.05.” Nearly everyone agrees antidepressants have a statistically significant effect – they do something. The dispute is over whether they have a clinically significant effect – the something they do is enough to make a real difference to real people)
  - Sakos 4y ago
    It's worth reading the article in its entirety because of how much information is summarized in one place. > They also note that Kirsch’s study lumps all antidepressants together. This isn’t necessarily wrong. But it isn’t necessarily right, either. For example, his study used both Serzone (believed to be a weak antidepressant, rarely used) and Paxil (believed to be a stronger antidepressant, commonly used). And in fact, by his study, Paxil showed an effect size of 0.47, compared to Serzone’s 0.21. But since the difference was not statistically significant, he averaged them together and said that “antidepressants are ineffective”. In fact, his study showed that Paxil was effective, but when you average it together with a very ineffective drug, the effect disappears. He can get away with this because of the arcana of statistical significance, but by the same arcana I can get away with not doing that. > So. In conclusion, everyone has mapped HAM-D numbers into words like “moderate” in totally contradictory ways, such that one person’s “mild” is another person’s “very severe”. Another person randomly decided that we can only call things “clinically significant” if they go above the nice round number of 0.5, then retracted this. So when people say “the effects of antidepressants are only clinically significant in severe depression”, what they mean is “the effects of antidepressants only reach a totally arbitrary number one guy made up and then retracted, in people whose HAM-D score is above whatever number I make up right now.” Depending on what number you choose and what word you make up to describe it, you can find that antidepressants are useful in moderate depression, or severe depression, or super-duper double-dog-severe depression, or whatever.
- alfiedotwtf 4y ago
  Anecdotal, but I know several (over 5) people whose lives would be hell without Zoloft, and some who have gone through multiple anti-depressants but stayed with Zoloft.
loudtieblahblah 4y ago
Some antidepressants work for some people for some time. Its often that folks have to try a bunch of them, each for 5week to 3 months at a time, with side effects often making them worse rather than better before landing on the "right one" And even then you end up having to periodically up the dose, then eventually stack it with other drugs to mitigate side effects before eventually it becomes ineffective and you have to start the process all over again. I don't see why bother when exercise has better results. Go lift big stone, make sad voice in head quiet. Go sit in hot room. Eat good Get sleep.
- Gordonjcp 4y ago
  > I don't see why bother when exercise has better results. Except it doesn't.
- gjulianm 4y ago
  The problem of depression is that it makes incredibly difficult to do those things, getting exercise, eating better, sleeping well, anything that makes you feel better. That's why people use antidepressants, because they aren't well enough to start doing other things to help themselves. Your advice ultimately boils down to "just don't be depressed" and that has never worked.
- Broken_Hippo 4y ago
  I don't see why bother when exercise has better results. Go lift big stone, make sad voice in head quiet. Go sit in hot room. Eat good Get sleep. Grand. So what you are telling me is that you've not experienced the sort of depression that makes some of this impossible, and you've been lucky enough that poverty hasn't kept you from doing some of these things. And honestly, folks don't periodically up the dose as a matter of course. They do not always become ineffective. Heck, people don't always stay on them for years. Yes, folks often have to try more than one - but folks also do this with migraine treatments and allergy medications and insulin (to a point). This isn't because the treatments are necessarily bad, but because we don't understand the reason for this difference and are still learning things about the human body. We shouldn't wait for a perfect cure or a perfect treatment - imperfect relief is still relief. I'd rather have ibuprofen temporarily take care of menstrual pain rather than have to suffer through it until it can be cured or until there is longer lasting/better relief. Same with other things. And as far as side effects: Since our cures and treatments are imperfect, we have to weigh side effects to the cure. Often, I'd rather not want to kill myself and I'd rather not be depressed, so some side effects are OK. The same with other things, though. I have MS. All the medications have side effects, sometimes serious ones. But they stop disease activity and make it much more likely that I'll be able to lead a full life with use of my limbs and sight. And folks do have to change medications for various reasons, but the drugs still help. I'll take it. Sure, I'd rather not have side effects but like I said, imperfect relief or help is better than none.
wongarsu 4y ago
I'd be surprised if depression turns out to have a singular cause or mechanism. It's simply a group of symptoms that often occur together. The way we currently speak about depression is as if we labeled the combination of fever, coughing and sweating as "the hots". You'd expect to quickly find remedies like "Tylenol reduces symptoms of the hots", followed a decade later by papers "the hots not caused by Tylenol imbalance", with people contradicting it with "I can't live without Tylenol, it's as important to me as insulin for a diabetic". Both can be right, Tylenol just happens to reduce the symptoms without doing anything about the cause. Any actual cure you find would appear to only work for a small portion of patients. Not because it's ineffective, but because "the hots" isn't one distinct illness, but a symptom of many possible conditions, and you have to use different strategies to cure each one.
- moron4hire 4y ago
  Yeah, any study that says something like "This specific SSRI doesn't work for some people, works massively well for others, therefore it's not an effective treatment" should really be tossed in the bin. It's funny that you mention Tylenol as an example, as acetaminophen/paracetamol is the only over-the-counter pain killer that works for me. Ibuprofen does literally nothing for me and I've had to convince my doctors to list it as an "allergy" on my medical records just so my health care providers will stop suggesting it. But that doesn't mean ibuprofen is not effective for other people. I was prescribed SSRIs for a while, back in a particular bad part of my life (financial stress, job I hated, lots of health problems with everyone in my family). If we're going to say that all SSRIs are basically placebo, then I was not in any mental mood to believe that anything a doctor would prescribe to me would be effective. And in my case, Wellbutrin was not. In fact, it had a very significant deleterious effect in that it made me a raging asshole. But Lexapro, on the other hand... night and day difference. (Thankfully, job changed, everyone's health got better, and now I'm no longer on anything other than blood pressure and cholesterol meds, which, come to think of it, is round-about treating the knock-on effects of my years of untreated depression). Placebo effect is never a large effect. If you see a large effect, it's pretty safe to say it's not placebo.
u320 4y ago
Yes, it's mostly an urban legend at this point. Really shoddy science journalism here.
hereme888 4y ago
We sort of do know some of the mechanisms why they work: they increase BDNF and stimulate certain serotonin receptors, allowing new and healthier neural connections and associations to be formed, helping people more easily snap out of old ways of thinking, similar to how psilocybin and other newer "drugs" help people snap out of depression. That's why antidepressants are ideally combined with CBT or other therapies that help people change their mindset.

As far as I'm aware, it's been known for decades that we don't actually know what causes depression, and that whilst we know that antidepressants work, we don't know why they work.

drooby 4y ago

How certain are we of this? I’ve seen many studies stating that things like Zoloft are actually no better than placebo. But placebo does work.. because it modifies our expectations.

alecbz 4y ago
I’m pretty sure other studies do find differences between SSRIs and placebo. I trust Scott Alexander’s take on this: https://slatestarcodex.com/2014/07/07/ssris-much-more-than-you-wanted-to-know/ https://slatestarcodex.com/2014/07/07/ssris-much-more-than-y... but the one-sentence answer definitely seems to be “it’s complicated” One good quote: > some people have decided that antidepressants’ effect size of 0.3 means they are “clinically insignificant”. > (please note that “clinically insignificant” is very different from “statistically insignificant” aka “has a p-value less than 0.05.” Nearly everyone agrees antidepressants have a statistically significant effect – they do something. The dispute is over whether they have a clinically significant effect – the something they do is enough to make a real difference to real people)
- Sakos 4y ago
  It's worth reading the article in its entirety because of how much information is summarized in one place. > They also note that Kirsch’s study lumps all antidepressants together. This isn’t necessarily wrong. But it isn’t necessarily right, either. For example, his study used both Serzone (believed to be a weak antidepressant, rarely used) and Paxil (believed to be a stronger antidepressant, commonly used). And in fact, by his study, Paxil showed an effect size of 0.47, compared to Serzone’s 0.21. But since the difference was not statistically significant, he averaged them together and said that “antidepressants are ineffective”. In fact, his study showed that Paxil was effective, but when you average it together with a very ineffective drug, the effect disappears. He can get away with this because of the arcana of statistical significance, but by the same arcana I can get away with not doing that. > So. In conclusion, everyone has mapped HAM-D numbers into words like “moderate” in totally contradictory ways, such that one person’s “mild” is another person’s “very severe”. Another person randomly decided that we can only call things “clinically significant” if they go above the nice round number of 0.5, then retracted this. So when people say “the effects of antidepressants are only clinically significant in severe depression”, what they mean is “the effects of antidepressants only reach a totally arbitrary number one guy made up and then retracted, in people whose HAM-D score is above whatever number I make up right now.” Depending on what number you choose and what word you make up to describe it, you can find that antidepressants are useful in moderate depression, or severe depression, or super-duper double-dog-severe depression, or whatever.
alfiedotwtf 4y ago
Anecdotal, but I know several (over 5) people whose lives would be hell without Zoloft, and some who have gone through multiple anti-depressants but stayed with Zoloft.

loudtieblahblah 4y ago

Some antidepressants work for some people for some time. Its often that folks have to try a bunch of them, each for 5week to 3 months at a time, with side effects often making them worse rather than better before landing on the "right one" And even then you end up having to periodically up the dose, then eventually stack it with other drugs to mitigate side effects before eventually it becomes ineffective and you have to start the process all over again. I don't see why bother when exercise has better results. Go lift big stone, make sad voice in head quiet. Go sit in hot room. Eat good Get sleep.

Gordonjcp 4y ago
> I don't see why bother when exercise has better results. Except it doesn't.
gjulianm 4y ago
The problem of depression is that it makes incredibly difficult to do those things, getting exercise, eating better, sleeping well, anything that makes you feel better. That's why people use antidepressants, because they aren't well enough to start doing other things to help themselves. Your advice ultimately boils down to "just don't be depressed" and that has never worked.
Broken_Hippo 4y ago
I don't see why bother when exercise has better results. Go lift big stone, make sad voice in head quiet. Go sit in hot room. Eat good Get sleep. Grand. So what you are telling me is that you've not experienced the sort of depression that makes some of this impossible, and you've been lucky enough that poverty hasn't kept you from doing some of these things. And honestly, folks don't periodically up the dose as a matter of course. They do not always become ineffective. Heck, people don't always stay on them for years. Yes, folks often have to try more than one - but folks also do this with migraine treatments and allergy medications and insulin (to a point). This isn't because the treatments are necessarily bad, but because we don't understand the reason for this difference and are still learning things about the human body. We shouldn't wait for a perfect cure or a perfect treatment - imperfect relief is still relief. I'd rather have ibuprofen temporarily take care of menstrual pain rather than have to suffer through it until it can be cured or until there is longer lasting/better relief. Same with other things. And as far as side effects: Since our cures and treatments are imperfect, we have to weigh side effects to the cure. Often, I'd rather not want to kill myself and I'd rather not be depressed, so some side effects are OK. The same with other things, though. I have MS. All the medications have side effects, sometimes serious ones. But they stop disease activity and make it much more likely that I'll be able to lead a full life with use of my limbs and sight. And folks do have to change medications for various reasons, but the drugs still help. I'll take it. Sure, I'd rather not have side effects but like I said, imperfect relief or help is better than none.

wongarsu 4y ago

I'd be surprised if depression turns out to have a singular cause or mechanism. It's simply a group of symptoms that often occur together. The way we currently speak about depression is as if we labeled the combination of fever, coughing and sweating as "the hots". You'd expect to quickly find remedies like "Tylenol reduces symptoms of the hots", followed a decade later by papers "the hots not caused by Tylenol imbalance", with people contradicting it with "I can't live without Tylenol, it's as important to me as insulin for a diabetic". Both can be right, Tylenol just happens to reduce the symptoms without doing anything about the cause. Any actual cure you find would appear to only work for a small portion of patients. Not because it's ineffective, but because "the hots" isn't one distinct illness, but a symptom of many possible conditions, and you have to use different strategies to cure each one.

moron4hire 4y ago
Yeah, any study that says something like "This specific SSRI doesn't work for some people, works massively well for others, therefore it's not an effective treatment" should really be tossed in the bin. It's funny that you mention Tylenol as an example, as acetaminophen/paracetamol is the only over-the-counter pain killer that works for me. Ibuprofen does literally nothing for me and I've had to convince my doctors to list it as an "allergy" on my medical records just so my health care providers will stop suggesting it. But that doesn't mean ibuprofen is not effective for other people. I was prescribed SSRIs for a while, back in a particular bad part of my life (financial stress, job I hated, lots of health problems with everyone in my family). If we're going to say that all SSRIs are basically placebo, then I was not in any mental mood to believe that anything a doctor would prescribe to me would be effective. And in my case, Wellbutrin was not. In fact, it had a very significant deleterious effect in that it made me a raging asshole. But Lexapro, on the other hand... night and day difference. (Thankfully, job changed, everyone's health got better, and now I'm no longer on anything other than blood pressure and cholesterol meds, which, come to think of it, is round-about treating the knock-on effects of my years of untreated depression). Placebo effect is never a large effect. If you see a large effect, it's pretty safe to say it's not placebo.

u320 4y ago

Yes, it's mostly an urban legend at this point. Really shoddy science journalism here.

hereme888 4y ago

We sort of do know some of the mechanisms why they work: they increase BDNF and stimulate certain serotonin receptors, allowing new and healthier neural connections and associations to be formed, helping people more easily snap out of old ways of thinking, similar to how psilocybin and other newer "drugs" help people snap out of depression. That's why antidepressants are ideally combined with CBT or other therapies that help people change their mindset.