6 ms·

Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place. The linked article says they have "small to moderat

Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place. The linked article says they have "small to moderate effectiveness", but this is being far too generous. The correct way to measure drug effectiveness is if the treatment meets the standard of a minimal important difference. I.e. you measure depression on various rating scales, like the 17-point HAM-D, and research suggests a minimal important difference (i.e. one patients and clinicians can actually notice) needs to be about 3-5 points. But the average effects of almost all antidepressants do not meet these thresholds, i.e. the effect actually appears practically invisible. [1] Then you'll get waffling like "oh, but it really has a big effect for some people", but, well, no, we've looked at that too, and the placebo groups get just as miraculous "big effects", i.e. evidence supporting the idea "they really help some people" is also largely lacking [2-3]. All the other attempted saves ("oh, but eventually you find one that works for you") are also not really well supported either [4]. Like, maybe they really help some people, but it is far, far less clear than most assume, and should be balanced with concerns like withdrawal and serious side effects like emotional blunting and sexual dysfunction. EDIT: And just to be clear to anyone doing a drive-by downvote thinking this is about recent asinine US politics, it emphatically isn't. There are serious methodological concerns here that desperately need to be communicated to the public. [1] https://pubmed.ncbi.nlm.nih.gov/33593736/ https://pubmed.ncbi.nlm.nih.gov/33593736/ [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC7451660/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7451660/ [3] https://pubmed.ncbi.nlm.nih.gov/33175895/ https://pubmed.ncbi.nlm.nih.gov/33175895/ [4] https://pmc.ncbi.nlm.nih.gov/articles/PMC11844611/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11844611/

Paracompact 1mo ago
On an academic level, we have reined in much of the excess enthusiasm in antidepressants that was courtesy of 90s-era pharmaceutical reps and ad men, but I don't think this revision ever occurred in the cultural consciousness at large.
- D-Machine 1mo ago
  Yup, I would agree. The meta-research / methodological research and awareness here is really quite impressive, even though its conclusions are a bit grim and not well-known.
  - jakebol 1mo ago
    A good book on this is Mind Fixers: Psychiatry's Troubled Search for the Biology of Mental Illness. Describing the history of how many of these classes of drugs came about is pretty eye opening, I would say the book is pretty nuanced in its conclusions. https://www.goodreads.com/en/book/show/40180010-mind-fixers https://www.goodreads.com/en/book/show/40180010-mind-fixers The title is a play on the Pulitzer prize winning article from the 80's. https://web.archive.org/web/20041125092022/http://www.bylinefranklin.com/writing/mindfixers.htm https://web.archive.org/web/20041125092022/http://www.byline...
- zer00eyz 1mo ago
  Have we reigned in the number of perscriptions? Because the 1 in 10 stat I find seems a bit low, at least in my circle, and those are the ones who are open about it. And the people I know have been on them approximately a decade. What baffles me is that a fair number of them triggered their own depressive episodes, and likely did need therapy and something at the time - but have all long since move past those "moments".
  - D-Machine 1mo ago
    I am not sure, but recommendations to prescribe in mild cases have quietly been reigned in a bit by e.g. NICE https://www.nice.org.uk/guidance/ng222/chapter/Recommendations https://www.nice.org.uk/guidance/ng222/chapter/Recommendatio....
- Rendello 1mo ago
  See also: The Serotonin Theory of Depression: a Systematic Umbrella Review of the Evidence (2022). It's worth reading the introduction and results in full, but here are two important quotes (footnote markers removed): > Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress. > The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence on these drugs. https://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0
  - zdragnar 1mo ago
    The conclusions in that were not universally accepted, and some critiques were rather damning: https://www.kcl.ac.uk/news/a-response-to-the-serotonin-theory-of-depression-a-systematic-umbrella-review-of-the-evidence https://www.kcl.ac.uk/news/a-response-to-the-serotonin-theor... Personally, I both agree that SSRI antidepressants were likely overprescribed early on, and disagree with the notion that the chemical imbalance theory is unsupported. N = 1, they can absolutely work. It took a few to find one that really did, hence I am certain it is not a placebo effect.
    - D-Machine 1mo ago
justonceokay 1mo ago
So did you take them and have a bad time? Because they definitely work for me and I doubt a placebo could have such a large effect on the 48 hour stomach pains I used to get alongside my frequent panic attacks. I find it funny that people complain about emotional blunting when that is the entire purpose of the drug. I would prefer not to live on the razors edge ever again. I’ve had chronic anxiety and depression ever since I was a child, though.
- D-Machine 1mo ago
  For some people the emotional blunting is desirable, especially as you said, if the problem is chronic anxiety. But for many other people, their depression is defined by a lack of positive affect and anhedonia, meaning that emotional blunting is literally making things worse. Depression is highly heterogenous, and I am glad the medication helped you.
- JoshTriplett 1mo ago
  > I find it funny that people complain about emotional blunting when that is the entire purpose of the drug. The ideal would be to blunt the negatives but not the positives. The effect of some of the older antidepressants can be to blunt both, across the board. Some of the newer atypical antidepressants can address depression without making everything flat.
- jakebol 1mo ago
  SSRIs have much more clinical evidence of efficacy for addressing anxiety disorders vs a placebo than depression. The effect size is ~0.7 vs 0.2 in meta studies.
  - martinald 1mo ago
    Totally agree, they really shouldn't be called antidepressants at all. Important to add tho that for many with depression they have comorbid anxiety and often the anxiety is harder to tolerate than depression, so removal of anxiety symptoms can be hugely beneficial. Also, IME they are dosed completely wrong. So many people seem to be on very low doses, which has no improvement on placebo in the studies I've read. Whereas, higher doses are _hugely_ better than placebo, especially for anxiety. What's worse is a lot/most studies on SSRIs in general often don't adjust for dose. Which seems like an enormous oversight to me.
burnte 1mo ago
> Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place. No, that will just hurt more people up front for longer. The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured. If you look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems. The truth is we took someone from being passively suicidal to functioning normally, and we fail to look at the self-reported problems, we just report them. The self reported problems tend to change from "I don't care about anything" to "I'm unhappy at my job" or "I'm stressed at how much I have to do with work and my kids and home." These are actually major improvements, the patient has gone from being actually clinically depressed to significant improvement but continued unhappiness with life circumstances as opposed to unhappiness with life in general. Antidepressants are amazing, we need to improve therapists and how they deal with medicated patients. Too many therapists dismiss meds and too many psychiatrists dismiss therapy. I've been in this space for a long time now, healthcare IT in the mental/behavioral health space. We're engaged in a long erm research study to help demonstrate the value of a tightly integrated therapy/psych team and more advanced treatments and when you get everyone in the room pulling in the same direction patient outcomes are amazing. One actual issue that antidepressants face is that they're not the only treatment, but many doctors are reluctant to move to TMS or esketamine, despite the amaing success rates they have with patients who have not had success with two or more drugs. If two drugs failed you, the third has a 14% chance of helping. The 4th is single digits. But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too. ADs aren't the problem, it's that we don't take mental health as serious as we take physical health.
- D-Machine 1mo ago
  > The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured. The truth is actually exactly the opposite, and I provided very high-quality evidence demonstrating this to be the case. You have nothing but bald assertions.
googaar 1mo ago
I can’t believe we’ve normalized anti depressants as a society. I’m about to get downvoted into oblivion for this take though. I’m not trying to discount mental health, I just think there are better solutions than drugs to fix your state of mind. Also think that some people are dealt a tougher hand than most, and that for a small subset of humans, anti depressants are the most fitting cure.
- D-Machine 1mo ago
  Agreed. They have to be significantly helping at least some, but we can't say who these people are for certain yet, or how many there really are. And yes, in some cases, no other options are possible, so even if the evidence is pretty dismal for their effectiveness, they are still broadly safe enough to definitely be worth a try. They probably just shouldn't be the first-line approach.
- SV_BubbleTime 1mo ago
  [flagged]
  - wredcoll 1mo ago
    There's hundreds of years of "depression isn't real and even if it was real the only treatment is to take a walk in the woods!!" and like a decade of "man, ssris are great, they really helped me". Public responses have probably not finished overcorrecting.
    - SV_BubbleTime 1mo ago
      Fair. But imo the issue with that might be that “just man up and go take a walk” may still be better advice than “hey kid with your underdeveloped brain… take this maybe psychoactive drug that absolutely changes your brain chemistry in ways we absolutely do not understand causing almost certain addiction with effectively zero supervision unless you self-report murderous and psychotic tendencies! Don’t mind that I’m making kickbacks on every subscription!!” In terms of possible damage to self and others. And to long term society.
marmarama 1mo ago
"As effective as placebo" does not mean worthless. As you point out, placebo antidepressants are fairly effective. It's a terrible bind. Patients want a pill to fix things, but if they know it's just a sugar pill, it doesn't work. It has to have active ingredients that might work. That's why there's little desire to change the status quo on antidepressants much. Anyone who reads the medical literature knows they're statistically underwhelming, but the experienced reality is that they help people a lot. Talking therapies, CBT, exercise are all good alternatives but they take time and effort that a depressed person might not be able to manage. An antidepressant prescription they can get in 15 minutes.
- D-Machine 1mo ago
  > As you point out, placebo antidepressants are fairly effective. This is a misunderstanding of concepts like regression to the mean, and also the active placebo elements involved. > but the experienced reality is that they help people a lot And the evidence is that the reality people think they are experiencing is wrong, i.e, they are improving and factually experiencing improvement, but misattributing the cause to the drug. > "As effective as placebo" does not mean worthless In one sense of worthless, perhaps, but since drugs have larger costs relative to placebo, well, we can argue they are worse than worseless in another. Better instead to talk about cost-benefit tradeoffs, number-needed-to-treat vs number-needed-to-harm and etc though, and try to get better at prescribing more carefully to those they clearly benefit.
- odyssey7 1mo ago
  It’s unethical to prescribe a patient a placebo in a way that suggests that what they are receiving is scientifically proven. In a clinical trial setting, you can prescribe a placebo, because the patient is fully aware and clearly consenting to the fact that they may receive a placebo. Lying to a patient, in a clinical setting, from a position of authority, is a completely different matter. The informed consent would be completely absent, the patient’s ability to make informed choices about their own healthcare would be undermined and withheld, and the provider would be deriving financial benefit from the patient and / or through insurance claims for what amounts to a scam. The patient, who would be seeking a treatment from a trusted expert, would believe that they are receiving proven treatments in exchange for their time, patience, money, reduced quality of life due to side effects, and opportunity costs in terms of not going to a different provider or trying something else, but in reality their provider would be misleading them. Some patients would even die as a result of taking a particular placebo and depending on it—either because of side effects or due to the lack of effectiveness—when they tragically would have been better off trying a different approach or medication. How could a patient possibly give informed consent in such a scenario, for one thing? How could they meaningfully compare treatment options and make their own informed choices when the advice they receive includes lies? Alas, some providers believe in placebo effects so much more strongly than their patients’ right to autonomy that when faced with complaints of side effects, they will just lie more and more to their patients in hopes that the side effects will go away, but that’s really just more gaslighting to people who are already in difficult situations.
aardvark92 1mo ago
My anecdotal experience going on and off Paxil is that it does work for me, and no matter how badly I want to live Rx-free, I consistently devolve into a moody mess without them.
Xortl 1mo ago
What's your opinion of the claim that antidepressants have small impact on people with mild to moderate depression, but significantly more impact on people with severe depression [1]? I ask as a nonexpert because this is a view I've read a few times from people I trust more than most, and I know two people who suffered from severe depression who credited SSRIs for getting them through. [1] https://pubmed.ncbi.nlm.nih.gov/20051569/ https://pubmed.ncbi.nlm.nih.gov/20051569/
- D-Machine 1mo ago
  Honestly, every time I look into if the "treatment by severity effect" is clearly established, I feel I come away only able to shrug. It is at least plausible, but hasn't been clearly established or refuted. What does seem clear to me is that the whole cost-benefit considerations change in favor of anti-depressants when the depression is severe. I wouldn't say anti-depressants should be first-line treatments for ordinary depression, but for severe depression, I think they are a very reasonable first-line option. Sure, they still might not help, but the costs / harms don't seem so bad compared to the potential costs / harms of leaving the severe major depression untreated, and the other options look all pretty terrible here too.
- D-Machine 1mo ago
  Wait, I finally found a paper that properly presents the results in a way that lets you decide for yourself! See figure 2 here: https://pmc.ncbi.nlm.nih.gov/articles/PMC9344377/#f2 https://pmc.ncbi.nlm.nih.gov/articles/PMC9344377/#f2, you want to focus on the second plot with the dotted and dashed lines. Basically, both placebo and drugs can have huge responses, but basically, for severe depression, yes, it looks like the drug is more likely to have a large positive effect than the placebo is likely to have a large positive effect. There are still a lot of limitations, main one being that study criteria generating the data for this would exclude most cases of really high severity actually seen in practice. Also "blinding" is mostly BS in these kinds of studies, and antidepressants have massive, noticeable effects, so the proper comparison is really an active placebo, and we really can't be sure the whole apparent antidepressant effect is basically just "woah, I can really feel this doing shit", basically, at some level, and this is still bad because the placebo vs. drug difference is still super tiny and below what we would consider typical minimal clinically important differences. So still hard to say. But, yeah, there is a good chance the drugs are more effective in severe cases, and, technically, you should definitely treat in a severe case.

Paracompact 1mo ago

On an academic level, we have reined in much of the excess enthusiasm in antidepressants that was courtesy of 90s-era pharmaceutical reps and ad men, but I don't think this revision ever occurred in the cultural consciousness at large.

D-Machine 1mo ago
Yup, I would agree. The meta-research / methodological research and awareness here is really quite impressive, even though its conclusions are a bit grim and not well-known.
- jakebol 1mo ago
  A good book on this is Mind Fixers: Psychiatry's Troubled Search for the Biology of Mental Illness. Describing the history of how many of these classes of drugs came about is pretty eye opening, I would say the book is pretty nuanced in its conclusions. https://www.goodreads.com/en/book/show/40180010-mind-fixers https://www.goodreads.com/en/book/show/40180010-mind-fixers The title is a play on the Pulitzer prize winning article from the 80's. https://web.archive.org/web/20041125092022/http://www.bylinefranklin.com/writing/mindfixers.htm https://web.archive.org/web/20041125092022/http://www.byline...
zer00eyz 1mo ago
Have we reigned in the number of perscriptions? Because the 1 in 10 stat I find seems a bit low, at least in my circle, and those are the ones who are open about it. And the people I know have been on them approximately a decade. What baffles me is that a fair number of them triggered their own depressive episodes, and likely did need therapy and something at the time - but have all long since move past those "moments".
- D-Machine 1mo ago
  I am not sure, but recommendations to prescribe in mild cases have quietly been reigned in a bit by e.g. NICE https://www.nice.org.uk/guidance/ng222/chapter/Recommendations https://www.nice.org.uk/guidance/ng222/chapter/Recommendatio....
Rendello 1mo ago
See also: The Serotonin Theory of Depression: a Systematic Umbrella Review of the Evidence (2022). It's worth reading the introduction and results in full, but here are two important quotes (footnote markers removed): > Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress. > The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence on these drugs. https://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0
- zdragnar 1mo ago
  The conclusions in that were not universally accepted, and some critiques were rather damning: https://www.kcl.ac.uk/news/a-response-to-the-serotonin-theory-of-depression-a-systematic-umbrella-review-of-the-evidence https://www.kcl.ac.uk/news/a-response-to-the-serotonin-theor... Personally, I both agree that SSRI antidepressants were likely overprescribed early on, and disagree with the notion that the chemical imbalance theory is unsupported. N = 1, they can absolutely work. It took a few to find one that really did, hence I am certain it is not a placebo effect.
  - D-Machine 1mo ago

justonceokay 1mo ago

So did you take them and have a bad time? Because they definitely work for me and I doubt a placebo could have such a large effect on the 48 hour stomach pains I used to get alongside my frequent panic attacks. I find it funny that people complain about emotional blunting when that is the entire purpose of the drug. I would prefer not to live on the razors edge ever again. I’ve had chronic anxiety and depression ever since I was a child, though.

D-Machine 1mo ago
For some people the emotional blunting is desirable, especially as you said, if the problem is chronic anxiety. But for many other people, their depression is defined by a lack of positive affect and anhedonia, meaning that emotional blunting is literally making things worse. Depression is highly heterogenous, and I am glad the medication helped you.
JoshTriplett 1mo ago
> I find it funny that people complain about emotional blunting when that is the entire purpose of the drug. The ideal would be to blunt the negatives but not the positives. The effect of some of the older antidepressants can be to blunt both, across the board. Some of the newer atypical antidepressants can address depression without making everything flat.
jakebol 1mo ago
SSRIs have much more clinical evidence of efficacy for addressing anxiety disorders vs a placebo than depression. The effect size is ~0.7 vs 0.2 in meta studies.
- martinald 1mo ago
  Totally agree, they really shouldn't be called antidepressants at all. Important to add tho that for many with depression they have comorbid anxiety and often the anxiety is harder to tolerate than depression, so removal of anxiety symptoms can be hugely beneficial. Also, IME they are dosed completely wrong. So many people seem to be on very low doses, which has no improvement on placebo in the studies I've read. Whereas, higher doses are _hugely_ better than placebo, especially for anxiety. What's worse is a lot/most studies on SSRIs in general often don't adjust for dose. Which seems like an enormous oversight to me.

burnte 1mo ago

> Best way to manage the withdrawal would be to dramatically reduce them being prescribed in the first place. No, that will just hurt more people up front for longer. The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured. If you look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems. The truth is we took someone from being passively suicidal to functioning normally, and we fail to look at the self-reported problems, we just report them. The self reported problems tend to change from "I don't care about anything" to "I'm unhappy at my job" or "I'm stressed at how much I have to do with work and my kids and home." These are actually major improvements, the patient has gone from being actually clinically depressed to significant improvement but continued unhappiness with life circumstances as opposed to unhappiness with life in general. Antidepressants are amazing, we need to improve therapists and how they deal with medicated patients. Too many therapists dismiss meds and too many psychiatrists dismiss therapy. I've been in this space for a long time now, healthcare IT in the mental/behavioral health space. We're engaged in a long erm research study to help demonstrate the value of a tightly integrated therapy/psych team and more advanced treatments and when you get everyone in the room pulling in the same direction patient outcomes are amazing. One actual issue that antidepressants face is that they're not the only treatment, but many doctors are reluctant to move to TMS or esketamine, despite the amaing success rates they have with patients who have not had success with two or more drugs. If two drugs failed you, the third has a 14% chance of helping. The 4th is single digits. But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too. ADs aren't the problem, it's that we don't take mental health as serious as we take physical health.

D-Machine 1mo ago
> The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured. The truth is actually exactly the opposite, and I provided very high-quality evidence demonstrating this to be the case. You have nothing but bald assertions.

googaar 1mo ago

I can’t believe we’ve normalized anti depressants as a society. I’m about to get downvoted into oblivion for this take though. I’m not trying to discount mental health, I just think there are better solutions than drugs to fix your state of mind. Also think that some people are dealt a tougher hand than most, and that for a small subset of humans, anti depressants are the most fitting cure.

D-Machine 1mo ago
Agreed. They have to be significantly helping at least some, but we can't say who these people are for certain yet, or how many there really are. And yes, in some cases, no other options are possible, so even if the evidence is pretty dismal for their effectiveness, they are still broadly safe enough to definitely be worth a try. They probably just shouldn't be the first-line approach.
SV_BubbleTime 1mo ago
[flagged]
- wredcoll 1mo ago
  There's hundreds of years of "depression isn't real and even if it was real the only treatment is to take a walk in the woods!!" and like a decade of "man, ssris are great, they really helped me". Public responses have probably not finished overcorrecting.
  - SV_BubbleTime 1mo ago
    Fair. But imo the issue with that might be that “just man up and go take a walk” may still be better advice than “hey kid with your underdeveloped brain… take this maybe psychoactive drug that absolutely changes your brain chemistry in ways we absolutely do not understand causing almost certain addiction with effectively zero supervision unless you self-report murderous and psychotic tendencies! Don’t mind that I’m making kickbacks on every subscription!!” In terms of possible damage to self and others. And to long term society.

marmarama 1mo ago

"As effective as placebo" does not mean worthless. As you point out, placebo antidepressants are fairly effective. It's a terrible bind. Patients want a pill to fix things, but if they know it's just a sugar pill, it doesn't work. It has to have active ingredients that might work. That's why there's little desire to change the status quo on antidepressants much. Anyone who reads the medical literature knows they're statistically underwhelming, but the experienced reality is that they help people a lot. Talking therapies, CBT, exercise are all good alternatives but they take time and effort that a depressed person might not be able to manage. An antidepressant prescription they can get in 15 minutes.

D-Machine 1mo ago
> As you point out, placebo antidepressants are fairly effective. This is a misunderstanding of concepts like regression to the mean, and also the active placebo elements involved. > but the experienced reality is that they help people a lot And the evidence is that the reality people think they are experiencing is wrong, i.e, they are improving and factually experiencing improvement, but misattributing the cause to the drug. > "As effective as placebo" does not mean worthless In one sense of worthless, perhaps, but since drugs have larger costs relative to placebo, well, we can argue they are worse than worseless in another. Better instead to talk about cost-benefit tradeoffs, number-needed-to-treat vs number-needed-to-harm and etc though, and try to get better at prescribing more carefully to those they clearly benefit.
odyssey7 1mo ago
It’s unethical to prescribe a patient a placebo in a way that suggests that what they are receiving is scientifically proven. In a clinical trial setting, you can prescribe a placebo, because the patient is fully aware and clearly consenting to the fact that they may receive a placebo. Lying to a patient, in a clinical setting, from a position of authority, is a completely different matter. The informed consent would be completely absent, the patient’s ability to make informed choices about their own healthcare would be undermined and withheld, and the provider would be deriving financial benefit from the patient and / or through insurance claims for what amounts to a scam. The patient, who would be seeking a treatment from a trusted expert, would believe that they are receiving proven treatments in exchange for their time, patience, money, reduced quality of life due to side effects, and opportunity costs in terms of not going to a different provider or trying something else, but in reality their provider would be misleading them. Some patients would even die as a result of taking a particular placebo and depending on it—either because of side effects or due to the lack of effectiveness—when they tragically would have been better off trying a different approach or medication. How could a patient possibly give informed consent in such a scenario, for one thing? How could they meaningfully compare treatment options and make their own informed choices when the advice they receive includes lies? Alas, some providers believe in placebo effects so much more strongly than their patients’ right to autonomy that when faced with complaints of side effects, they will just lie more and more to their patients in hopes that the side effects will go away, but that’s really just more gaslighting to people who are already in difficult situations.

aardvark92 1mo ago

My anecdotal experience going on and off Paxil is that it does work for me, and no matter how badly I want to live Rx-free, I consistently devolve into a moody mess without them.

Xortl 1mo ago

What's your opinion of the claim that antidepressants have small impact on people with mild to moderate depression, but significantly more impact on people with severe depression [1]? I ask as a nonexpert because this is a view I've read a few times from people I trust more than most, and I know two people who suffered from severe depression who credited SSRIs for getting them through. [1] https://pubmed.ncbi.nlm.nih.gov/20051569/ https://pubmed.ncbi.nlm.nih.gov/20051569/

D-Machine 1mo ago
Honestly, every time I look into if the "treatment by severity effect" is clearly established, I feel I come away only able to shrug. It is at least plausible, but hasn't been clearly established or refuted. What does seem clear to me is that the whole cost-benefit considerations change in favor of anti-depressants when the depression is severe. I wouldn't say anti-depressants should be first-line treatments for ordinary depression, but for severe depression, I think they are a very reasonable first-line option. Sure, they still might not help, but the costs / harms don't seem so bad compared to the potential costs / harms of leaving the severe major depression untreated, and the other options look all pretty terrible here too.
D-Machine 1mo ago
Wait, I finally found a paper that properly presents the results in a way that lets you decide for yourself! See figure 2 here: https://pmc.ncbi.nlm.nih.gov/articles/PMC9344377/#f2 https://pmc.ncbi.nlm.nih.gov/articles/PMC9344377/#f2, you want to focus on the second plot with the dotted and dashed lines. Basically, both placebo and drugs can have huge responses, but basically, for severe depression, yes, it looks like the drug is more likely to have a large positive effect than the placebo is likely to have a large positive effect. There are still a lot of limitations, main one being that study criteria generating the data for this would exclude most cases of really high severity actually seen in practice. Also "blinding" is mostly BS in these kinds of studies, and antidepressants have massive, noticeable effects, so the proper comparison is really an active placebo, and we really can't be sure the whole apparent antidepressant effect is basically just "woah, I can really feel this doing shit", basically, at some level, and this is still bad because the placebo vs. drug difference is still super tiny and below what we would consider typical minimal clinically important differences. So still hard to say. But, yeah, there is a good chance the drugs are more effective in severe cases, and, technically, you should definitely treat in a severe case.