8 ms·

SSRIs aren’t shown to be much better than placebo and are shown to be about as effective as therapy — which is actually durable. There’s also rates of sexual s

SSRIs aren’t shown to be much better than placebo and are shown to be about as effective as therapy — which is actually durable. There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. In fact industry data shows a smaller gap between SSRIs and placebo than FDA data. See Figure 1. [2] The problem with SSRIs is that serotonin receptors are all over the body including in the gonads and they play a large role in appetite regulation. They do something but it’s not nearly what people assume. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC6007725/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6007725/ [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC4592645/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4592645/

Aurornis 2y ago
> SSRIs aren’t shown to be much better than placebo "Not much better than placebo" is burying the lede. The real problem is that placebo performs very well in depression studies. It's a well studied phenomenon. Effective antidepressants are marginally better than placebo in the studies because the placebo group improves so much, not because the antidepressants don't do anything. > and are shown to be about as effective as therapy — which is actually durable. False dichotomy. The recommendation is for people on SSRIs to also do therapy. You don't have to choose one or the other. > There’s also rates of sexual side effects in excess of 70% [1] If you read further in your [1] you'll see that the rate of side effects is not "in excess of 70%" but lower, and it depends on both the medication and the dose. Switching medications and changing doses is often sufficient to ameliorate some or all of these effects. That paper also mentions newer alternatives such as Vilazodone (SSRI plus 5-HT1A action) which are shown to have lower incidence of these side effects. > and they cause weight gain which is separately associated with depression. SSRIs aren't really associated with weight gain once you exclude the older ones like Paroxetine which have anticholinergic effects. A lot of studies find statistically insignificant weight loss or slight gain. Weight gain is really a negligible decision factor in modern SSRI treatment: https://www.ccjm.org/content/ccjom/70/7/314.full.pdf https://www.ccjm.org/content/ccjom/70/7/314.full.pdf There's a lot of misinformed fear mongering in your comment.
- treis 2y ago
  >Effective antidepressants are marginally better than placebo in the studies because the placebo group improves so much, not because the antidepressants don't do anything. Not outperforming a placebo means they don't actually do anything.
  - Blackthorn 2y ago
    Marginally better means they do, in fact, outperform.
    - arcticbull 2y ago
      By like, a couple of percent, yes. So the question is, do the side-effects outweigh the very marginal difference. That's a decision you have to make for yourself.
  - mike_ivanov 2y ago
    Now do the same outside of the clinical conditions, in the patients' natural environment -- and compare the results.
  - specialist 2y ago
    There's 3 choices. Both placebos and SSRI perform better than doing nothing.
  - Johanx64 2y ago
    > Not outperforming a placebo means they don't actually do anything. SSRIs are potent pharmaceutical drugs that have multiple, very strong effects. For example, Setraline (SSRI) is one of the most effective drugs to treat premature ejaculation. It used to be prescribed for exactly this purpose (and maybe still is). If anything, this is one of the most pronounced and easily measurable effects of SSRIs. If I took 25mg of setraline per day (extremely small dose) for a week, it would become impossible to ejaculate. It also has a whole multitude of other effects that are more dependent on individual (age, gender, bodyweight, etc), some other effects for males are -> crushing testosterone levels, weakness. For me personally, it turns me extremely, extremely emotional, makes me able to sleep all the time, and mentally turns you into a zombie where your lifes dreams and aspirations just disappear. Does it help with depression? I would say no. That however doesn't mean it doesn't do anyting, because they do all sorts of things. It is a very potent and poorly understood pharmaceutical.
bluescrn 2y ago
> There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. As an obese depression-sufferer currently taking Mounjaro, these new weight loss drugs seem way more effective at treating the depression than SSRIs. Actually losing a bit of weight with previously-unimaginable ease actually offers some genuine hope. It's not quite a miracle drug, the side-effects can be unpleasant, but when you're severely overweight they seem a small price to pay.
- IX-103 2y ago
  Yeah, the new "weight-loss" drugs seem to have significant psycho-active effects on the dopamine reward pathway. That seems like it may provide a more direct treatment than SSRIs.
  - deleted 2y ago
    [deleted]
  - arcticbull 2y ago
    Yeah calling them weight-loss drugs seems to really be under-selling them. I suspect the anti-depressant action has more to do with BDNF-TrkB and IL-6 signaling though!
- arcticbull 2y ago
  Yep they do, in part because of the depression-obesity axis but also likely via an independent mechanism. They do a couple of interesting things. For one, they seem to have a systemic anti-inflammatory effect. They lower the levels of TNF-alpha and interleukins like IL-6. High levels of TNF-alpha and IL-6 are implicated in depression. > Various meta-analyses have consistently reported increased IL-6 and TNF-α concentrations in depressed patients compared to healthy controls. IL-6 and TNF-α are associated with specific symptoms and behaviors that co-occur with depression. [1] They also increase the levels of brain-derived neurotrophic factor (BDNF) and BDNF-TrkB signalling is also implicated in depression, especially major depression. [2] Second, GLP-1 RAs yield similar changes in BDNF, TNF-alpha and interleukin levels you see in atypical antidepressants and anxiolytics like the old Soviet-era Semax [3] and Selank [4]. The former is a peptide analog of ACTH and the latter a peptide analog of tuftsin. Consequently it makes perfect sense to me that GLP-1 RAs would also have atypical antidepressant activity via the same pathway. There's a lot more to GLP-1 RAs and depression than just making you feel better about yourself as a result of your weight loss, and I suspect we're going to hear a lot more about this in the coming years. They also get you to the point where you feel good enough to exercise, which increases the levels of serotonin, dopamine and noradrenaline, and is also as effective as antidepressants. Unfortunately, depressed people can't bring themselves to exercise. Breaking that cycle so you can and do can only help more. I've done a lot of digging on all this stuff over the last few years, it's really fascinating. tl;dr: There's definitely something to your lived experience. Congratulations on getting started on your journey. [1] https://www.nature.com/articles/s41598-025-85514-0 https://www.nature.com/articles/s41598-025-85514-0 [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ [3] https://www.cambridge.org/core/journals/cns-spectrums/article/therapeutic-possibility-of-semax-for-depression/E2293226BFBE224272AA7C8CE60AD7C0 https://www.cambridge.org/core/journals/cns-spectrums/articl... [4] https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/
Blackthorn 2y ago
> SSRIs aren’t shown to be much better than placebo Or in other words: it's better than placebo.
- cess11 2y ago
  How did you determine that the side and negative social effects aren't large enough to outweigh that difference?
- Mistletoe 2y ago
  When you use an active placebo like atropine, something that makes you feel "different" like SSRIs do, it is even worse. https://pubmed.ncbi.nlm.nih.gov/7037102/ https://pubmed.ncbi.nlm.nih.gov/7037102/ https://sci-hub.se/https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)70280-9/abstract https://sci-hub.se/https://www.thelancet.com/journals/lanpsy... >Many years ago, adequately blinded trials of tricyclic antidepressants were done, in which the placebo contained atropine, which causes dryness in the mouth like the active drugs do. These trials reported very small, clinically insignificant effects of tricyclic antidepressants compared with placebo (standardised mean difference 0·17, 95% CI 0·00–0·34).
  - usednet 2y ago
    https://www.astralcodexten.com/p/all-medications-are-insignificant https://www.astralcodexten.com/p/all-medications-are-insigni...
  - NickM 2y ago
    Exactly this. Many double blind studies are completely broken due to side effects triggering a stronger placebo response, and this is an especially huge problem for drugs like SSRIs where a placebo gets you about 80% of the benefit of the actual drug. Similar to the study you linked, there was a more recent study where they found that for the SSRI escitalopram (aka Lexapro), the benefits disappear when you lie and tell people that they're receiving an active placebo that mimics the side effects of an SSRI. That is, if people don't actually think they're taking an SSRI, they don't get any benefit. https://app.dimensions.ai/details/publication/pub.1142338190 https://app.dimensions.ai/details/publication/pub.1142338190
aeturnum 2y ago
> The problem with SSRIs [...] Yah, serotonin is involved in a lot! I don't think that's a problem? You aren't saying it directly, but I feel like you are pointing to SSRI side effects as if they invalidate that SSRIs help depression. That's not true! People can choose if they want therapy or SSRIs or both. If your doctor has been telling you serotonin dis-regulation directly causes depression that's probably wrong - but if they tell you that SSRIs help many depressed people that's right.
- arcticbull 2y ago
  I'm pointing at it as a problem because that's what causes the e.g. sexual side effects. It's why you don't get them from, e.g. bupropion (an NDRI and nicotinic receptor antagonist) that act on the noradrenergic, dopaminergic and nicotinic systems - and not on seratonergic. Regarding helping people with depression, the numbers don't really support a strong effect especially against an active placebo that makes you feel different like atropine. [edit] Don't misunderstand, I'm not saying that there's not a role for pharmaceuticals. Just that the data for SSRIs specifically is not nearly as compelling as the quantity of prescriptions for it would have you believe, and they probably shouldn't be front-line treatment.
  - aeturnum 2y ago
    Oh! Well sure SSRIs are over-prescribed and shouldn't be a "front line" treatment. I agree with that. That, to me, is a very different question. What we call "depression" seems to be a complex bundle of brain mess. We group by symptom but unfortunately need to treat by cause and they are not 1:1. So SSRIs are a tool "we" have on a population level - but each individual depressed person is their own situation. Remember that "better than a placebo" is a population-level measure. Individual people will find a SSRI helpful or hindering as they go. I think you are mixing...policy ("we shouldn't assume this works for everyone") with drug efficacy ("SSRIs don't help more than a sugar pill"). How each persons' depression works is different and up-regulating serotonin is helpful to some subset of people. We don't know why and it's not the whole population, but talking about them in this way is not helpful in my mind.
alpaca128 2y ago
It sounds like you think therapy can replace medication just because some numbers on a spreadsheet fit together. If that's the case I have to tell you that you're misled and I suggest you talk to some real people who actually had to deal with depression. Antidepressants can be a life-changer in ways that placebo could never match, and can be necessary to even be able to go see a therapist.
IX-103 2y ago
If you ask any practicing psychiatrist, you'll see that they are aware of the problems with SSRIs. They tell their patients that they may need to try several drinks until they find one right for them. The way you presented those statistics is very misleading. The 70% number for sexual side effects you quoted was actually for patients that stopped taking at last once drug for that reason. Typically patients will have to try 2-3 drugs to find something that works for them and may need to transition to a new drug when the old one is no longer effective. So it's not like those patients are facing those side effects on an ongoing basis. It's just during the initial period when they are adjusting things. I suspect that the reason why SSRIs perform so poorly in the studies is that the amount of variation in these receptor targets is high, so some drugs actually are effectively placebos to a large fraction of people. But for other individuals they are a miracle. And if you multiply that by the number of different drugs, you can almost always find one of them that helps each patient. This goes into your assertion about "serotonin receptors are all over the body". That's something doctors and medical researchers have known for a long time. That's why the SSRIs are tailored to the specific variants of the serotonin receptors present in the organs they want to influence. That doesn't mean they have no effect on the receptors in other organs, but that the effect is minimized to the extent possible. But I suspect that one limitation in how tightly we're able to target the right receptors has to do with individual variation - make it specific enough that it doesn't affect other organs then it doesn't work for anybody with the slightest variation in target receptor shape. But I agree that the role serotonin plays in depression is poorly understood. But I don't agree with the implication of your post that we should stop using them. They are often helpful even in cases where therapy is insufficient, and improve outcomes in conjunction with therapy. They are too useful a tool to discard, even with their issues.
jdietrich 2y ago
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?
- agensaequivocum 2y ago
  Lots of morning, midday, and evening sun on as much skin as possible. Lot's of supplemental inositol
- kypro 2y ago
  > 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.
amanaplanacanal 2y ago
Don't hold your breath for the sudden availability of thousands to millions more therapists becoming available. I'd love to see a lot more spending for mental health care, but it ain't going to happen. SSRIs are cheap and easy, so that's what we get
- mulderc 2y ago
  I will say that an LLM helped me work through some past trauma in a way therapists never could. I don’t think anyone should use these models in place of therapy but I was pretty amazed at how quickly it helped me with an issue I had been having for a long time.
thatoneguy 2y ago
My-not-much-better-than-placebo sertraline sure has been working its placebo-like magic for 30 years next year. How long are these double-blind studies? Surely they're not years long to show that the placebo effect is maintained over a decade or something.
vjk800 2y ago
> There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. I can't find the source now - if someone can, please help me here - but there was a theory that SSRIs work exactly because of the sexual "side effects" (which means that it's not actually a side effect but the main effect). The idea would be that the depression is due to some kind of deeply rooted sexual frustration, which is alleviated when the sex drive vanishes.
- Johanx64 2y ago
  There's also a theory that the reason why SSRIs end up not helping or making things worse in the end is that for males they crush testosterone levels, and if they didn't, they might have been an effective treatment otherwise.
openasocket 2y ago
That’s true, but slightly misleading. Yes, SSRIs are not much better than a placebo, because a placebo is surprisingly effective against depression! It’s not so much that SSRIs are ineffective, as the fact that the placebo effect seems to be especially strong in depression cases

Aurornis 2y ago

> SSRIs aren’t shown to be much better than placebo "Not much better than placebo" is burying the lede. The real problem is that placebo performs very well in depression studies. It's a well studied phenomenon. Effective antidepressants are marginally better than placebo in the studies because the placebo group improves so much, not because the antidepressants don't do anything. > and are shown to be about as effective as therapy — which is actually durable. False dichotomy. The recommendation is for people on SSRIs to also do therapy. You don't have to choose one or the other. > There’s also rates of sexual side effects in excess of 70% [1] If you read further in your [1] you'll see that the rate of side effects is not "in excess of 70%" but lower, and it depends on both the medication and the dose. Switching medications and changing doses is often sufficient to ameliorate some or all of these effects. That paper also mentions newer alternatives such as Vilazodone (SSRI plus 5-HT1A action) which are shown to have lower incidence of these side effects. > and they cause weight gain which is separately associated with depression. SSRIs aren't really associated with weight gain once you exclude the older ones like Paroxetine which have anticholinergic effects. A lot of studies find statistically insignificant weight loss or slight gain. Weight gain is really a negligible decision factor in modern SSRI treatment: https://www.ccjm.org/content/ccjom/70/7/314.full.pdf https://www.ccjm.org/content/ccjom/70/7/314.full.pdf There's a lot of misinformed fear mongering in your comment.

treis 2y ago
>Effective antidepressants are marginally better than placebo in the studies because the placebo group improves so much, not because the antidepressants don't do anything. Not outperforming a placebo means they don't actually do anything.
- Blackthorn 2y ago
  Marginally better means they do, in fact, outperform.
  - arcticbull 2y ago
    By like, a couple of percent, yes. So the question is, do the side-effects outweigh the very marginal difference. That's a decision you have to make for yourself.
- mike_ivanov 2y ago
  Now do the same outside of the clinical conditions, in the patients' natural environment -- and compare the results.
- specialist 2y ago
  There's 3 choices. Both placebos and SSRI perform better than doing nothing.
- Johanx64 2y ago
  > Not outperforming a placebo means they don't actually do anything. SSRIs are potent pharmaceutical drugs that have multiple, very strong effects. For example, Setraline (SSRI) is one of the most effective drugs to treat premature ejaculation. It used to be prescribed for exactly this purpose (and maybe still is). If anything, this is one of the most pronounced and easily measurable effects of SSRIs. If I took 25mg of setraline per day (extremely small dose) for a week, it would become impossible to ejaculate. It also has a whole multitude of other effects that are more dependent on individual (age, gender, bodyweight, etc), some other effects for males are -> crushing testosterone levels, weakness. For me personally, it turns me extremely, extremely emotional, makes me able to sleep all the time, and mentally turns you into a zombie where your lifes dreams and aspirations just disappear. Does it help with depression? I would say no. That however doesn't mean it doesn't do anyting, because they do all sorts of things. It is a very potent and poorly understood pharmaceutical.

bluescrn 2y ago

> There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. As an obese depression-sufferer currently taking Mounjaro, these new weight loss drugs seem way more effective at treating the depression than SSRIs. Actually losing a bit of weight with previously-unimaginable ease actually offers some genuine hope. It's not quite a miracle drug, the side-effects can be unpleasant, but when you're severely overweight they seem a small price to pay.

IX-103 2y ago
Yeah, the new "weight-loss" drugs seem to have significant psycho-active effects on the dopamine reward pathway. That seems like it may provide a more direct treatment than SSRIs.
- deleted 2y ago
  [deleted]
- arcticbull 2y ago
  Yeah calling them weight-loss drugs seems to really be under-selling them. I suspect the anti-depressant action has more to do with BDNF-TrkB and IL-6 signaling though!
arcticbull 2y ago
Yep they do, in part because of the depression-obesity axis but also likely via an independent mechanism. They do a couple of interesting things. For one, they seem to have a systemic anti-inflammatory effect. They lower the levels of TNF-alpha and interleukins like IL-6. High levels of TNF-alpha and IL-6 are implicated in depression. > Various meta-analyses have consistently reported increased IL-6 and TNF-α concentrations in depressed patients compared to healthy controls. IL-6 and TNF-α are associated with specific symptoms and behaviors that co-occur with depression. [1] They also increase the levels of brain-derived neurotrophic factor (BDNF) and BDNF-TrkB signalling is also implicated in depression, especially major depression. [2] Second, GLP-1 RAs yield similar changes in BDNF, TNF-alpha and interleukin levels you see in atypical antidepressants and anxiolytics like the old Soviet-era Semax [3] and Selank [4]. The former is a peptide analog of ACTH and the latter a peptide analog of tuftsin. Consequently it makes perfect sense to me that GLP-1 RAs would also have atypical antidepressant activity via the same pathway. There's a lot more to GLP-1 RAs and depression than just making you feel better about yourself as a result of your weight loss, and I suspect we're going to hear a lot more about this in the coming years. They also get you to the point where you feel good enough to exercise, which increases the levels of serotonin, dopamine and noradrenaline, and is also as effective as antidepressants. Unfortunately, depressed people can't bring themselves to exercise. Breaking that cycle so you can and do can only help more. I've done a lot of digging on all this stuff over the last few years, it's really fascinating. tl;dr: There's definitely something to your lived experience. Congratulations on getting started on your journey. [1] https://www.nature.com/articles/s41598-025-85514-0 https://www.nature.com/articles/s41598-025-85514-0 [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/ [3] https://www.cambridge.org/core/journals/cns-spectrums/article/therapeutic-possibility-of-semax-for-depression/E2293226BFBE224272AA7C8CE60AD7C0 https://www.cambridge.org/core/journals/cns-spectrums/articl... [4] https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5322660/

Blackthorn 2y ago

> SSRIs aren’t shown to be much better than placebo Or in other words: it's better than placebo.

cess11 2y ago
How did you determine that the side and negative social effects aren't large enough to outweigh that difference?
Mistletoe 2y ago
When you use an active placebo like atropine, something that makes you feel "different" like SSRIs do, it is even worse. https://pubmed.ncbi.nlm.nih.gov/7037102/ https://pubmed.ncbi.nlm.nih.gov/7037102/ https://sci-hub.se/https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)70280-9/abstract https://sci-hub.se/https://www.thelancet.com/journals/lanpsy... >Many years ago, adequately blinded trials of tricyclic antidepressants were done, in which the placebo contained atropine, which causes dryness in the mouth like the active drugs do. These trials reported very small, clinically insignificant effects of tricyclic antidepressants compared with placebo (standardised mean difference 0·17, 95% CI 0·00–0·34).
- usednet 2y ago
  https://www.astralcodexten.com/p/all-medications-are-insignificant https://www.astralcodexten.com/p/all-medications-are-insigni...
- NickM 2y ago
  Exactly this. Many double blind studies are completely broken due to side effects triggering a stronger placebo response, and this is an especially huge problem for drugs like SSRIs where a placebo gets you about 80% of the benefit of the actual drug. Similar to the study you linked, there was a more recent study where they found that for the SSRI escitalopram (aka Lexapro), the benefits disappear when you lie and tell people that they're receiving an active placebo that mimics the side effects of an SSRI. That is, if people don't actually think they're taking an SSRI, they don't get any benefit. https://app.dimensions.ai/details/publication/pub.1142338190 https://app.dimensions.ai/details/publication/pub.1142338190

aeturnum 2y ago

> The problem with SSRIs [...] Yah, serotonin is involved in a lot! I don't think that's a problem? You aren't saying it directly, but I feel like you are pointing to SSRI side effects as if they invalidate that SSRIs help depression. That's not true! People can choose if they want therapy or SSRIs or both. If your doctor has been telling you serotonin dis-regulation directly causes depression that's probably wrong - but if they tell you that SSRIs help many depressed people that's right.

arcticbull 2y ago
I'm pointing at it as a problem because that's what causes the e.g. sexual side effects. It's why you don't get them from, e.g. bupropion (an NDRI and nicotinic receptor antagonist) that act on the noradrenergic, dopaminergic and nicotinic systems - and not on seratonergic. Regarding helping people with depression, the numbers don't really support a strong effect especially against an active placebo that makes you feel different like atropine. [edit] Don't misunderstand, I'm not saying that there's not a role for pharmaceuticals. Just that the data for SSRIs specifically is not nearly as compelling as the quantity of prescriptions for it would have you believe, and they probably shouldn't be front-line treatment.
- aeturnum 2y ago
  Oh! Well sure SSRIs are over-prescribed and shouldn't be a "front line" treatment. I agree with that. That, to me, is a very different question. What we call "depression" seems to be a complex bundle of brain mess. We group by symptom but unfortunately need to treat by cause and they are not 1:1. So SSRIs are a tool "we" have on a population level - but each individual depressed person is their own situation. Remember that "better than a placebo" is a population-level measure. Individual people will find a SSRI helpful or hindering as they go. I think you are mixing...policy ("we shouldn't assume this works for everyone") with drug efficacy ("SSRIs don't help more than a sugar pill"). How each persons' depression works is different and up-regulating serotonin is helpful to some subset of people. We don't know why and it's not the whole population, but talking about them in this way is not helpful in my mind.

alpaca128 2y ago

It sounds like you think therapy can replace medication just because some numbers on a spreadsheet fit together. If that's the case I have to tell you that you're misled and I suggest you talk to some real people who actually had to deal with depression. Antidepressants can be a life-changer in ways that placebo could never match, and can be necessary to even be able to go see a therapist.

IX-103 2y ago

If you ask any practicing psychiatrist, you'll see that they are aware of the problems with SSRIs. They tell their patients that they may need to try several drinks until they find one right for them. The way you presented those statistics is very misleading. The 70% number for sexual side effects you quoted was actually for patients that stopped taking at last once drug for that reason. Typically patients will have to try 2-3 drugs to find something that works for them and may need to transition to a new drug when the old one is no longer effective. So it's not like those patients are facing those side effects on an ongoing basis. It's just during the initial period when they are adjusting things. I suspect that the reason why SSRIs perform so poorly in the studies is that the amount of variation in these receptor targets is high, so some drugs actually are effectively placebos to a large fraction of people. But for other individuals they are a miracle. And if you multiply that by the number of different drugs, you can almost always find one of them that helps each patient. This goes into your assertion about "serotonin receptors are all over the body". That's something doctors and medical researchers have known for a long time. That's why the SSRIs are tailored to the specific variants of the serotonin receptors present in the organs they want to influence. That doesn't mean they have no effect on the receptors in other organs, but that the effect is minimized to the extent possible. But I suspect that one limitation in how tightly we're able to target the right receptors has to do with individual variation - make it specific enough that it doesn't affect other organs then it doesn't work for anybody with the slightest variation in target receptor shape. But I agree that the role serotonin plays in depression is poorly understood. But I don't agree with the implication of your post that we should stop using them. They are often helpful even in cases where therapy is insufficient, and improve outcomes in conjunction with therapy. They are too useful a tool to discard, even with their issues.

jdietrich 2y ago

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?

agensaequivocum 2y ago
Lots of morning, midday, and evening sun on as much skin as possible. Lot's of supplemental inositol
kypro 2y ago
> 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.

amanaplanacanal 2y ago

Don't hold your breath for the sudden availability of thousands to millions more therapists becoming available. I'd love to see a lot more spending for mental health care, but it ain't going to happen. SSRIs are cheap and easy, so that's what we get

mulderc 2y ago
I will say that an LLM helped me work through some past trauma in a way therapists never could. I don’t think anyone should use these models in place of therapy but I was pretty amazed at how quickly it helped me with an issue I had been having for a long time.

thatoneguy 2y ago

My-not-much-better-than-placebo sertraline sure has been working its placebo-like magic for 30 years next year. How long are these double-blind studies? Surely they're not years long to show that the placebo effect is maintained over a decade or something.

vjk800 2y ago

> There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression. I can't find the source now - if someone can, please help me here - but there was a theory that SSRIs work exactly because of the sexual "side effects" (which means that it's not actually a side effect but the main effect). The idea would be that the depression is due to some kind of deeply rooted sexual frustration, which is alleviated when the sex drive vanishes.

Johanx64 2y ago
There's also a theory that the reason why SSRIs end up not helping or making things worse in the end is that for males they crush testosterone levels, and if they didn't, they might have been an effective treatment otherwise.

openasocket 2y ago

That’s true, but slightly misleading. Yes, SSRIs are not much better than a placebo, because a placebo is surprisingly effective against depression! It’s not so much that SSRIs are ineffective, as the fact that the placebo effect seems to be especially strong in depression cases