4 ms·

> 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
crdrost 2y ago
> Finally, Jauhar et al. argue that serotonin must be involved in depression because drugs which target the serotonin system are effective and other authors also argue that antidepressants ‘work’. However, whether antidepressants produce a genuine and useful pharmacological effect that is independent of the placebo effect, has not been established. Antidepressants show marginal differences from placebo, which do not fulfil criteria for clinical relevance, and may represent amplified placebo effects due to unblinding [31,32,33]. It is hard to reconcile even the most generous appraisal of their efficacy with the vast numbers of people now taking them. Contrary to Bartova et al’s claims, the idea that antidepressants reduce suicide has not been established, and evidence from randomised trials suggests they increase the risk of suicidality in some age groups [34, 35]. -- Monicreff et al. (2023), https://www.nature.com/articles/s41380-023-02094-z https://www.nature.com/articles/s41380-023-02094-z
- alpaca128 2y ago
  > whether antidepressants produce a genuine and useful pharmacological effect that is independent of the placebo effect, has not been established As someone who has experience with antidepressants that goes beyond looking at numbers I can assure you that effect has been established very clearly. And it has nothing to do with placebo, only the second medication was the one that worked - it did more in three days than the first one after months on the highest dose. These studies sound to me like the attempts to find out whether life exists on a planet by analyzing some light spectrum through a telescope. I am sure they are useful but they seem a bit blind to what's actually going on in real life.
  - NickM 2y ago
    Keep in mind that studies find a strong effect for placebos: the numbers are not saying "these pills do nothing" they're saying "these pills seem to do a lot, but placebos do almost as much". Obviously the effect feels extremely real to you, but we wouldn't see a strong placebo effect in the numbers if people on placebos didn't genuinely feel much better. I get that it feels like the second drug worked much better, but expectancy effects and internal narratives are extremely strong, and they're impossible to untangle at the level of an individual.
zero_shift 2y ago
But are they better than e.g. tricyclics, MAOIs? Placebo comparisons aren't very informative for patients when there are other existing drugs.

How did you determine that the side and negative social effects aren't large enough to outweigh that difference?

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

crdrost 2y ago

> Finally, Jauhar et al. argue that serotonin must be involved in depression because drugs which target the serotonin system are effective and other authors also argue that antidepressants ‘work’. However, whether antidepressants produce a genuine and useful pharmacological effect that is independent of the placebo effect, has not been established. Antidepressants show marginal differences from placebo, which do not fulfil criteria for clinical relevance, and may represent amplified placebo effects due to unblinding [31,32,33]. It is hard to reconcile even the most generous appraisal of their efficacy with the vast numbers of people now taking them. Contrary to Bartova et al’s claims, the idea that antidepressants reduce suicide has not been established, and evidence from randomised trials suggests they increase the risk of suicidality in some age groups [34, 35]. -- Monicreff et al. (2023), https://www.nature.com/articles/s41380-023-02094-z https://www.nature.com/articles/s41380-023-02094-z

alpaca128 2y ago
> whether antidepressants produce a genuine and useful pharmacological effect that is independent of the placebo effect, has not been established As someone who has experience with antidepressants that goes beyond looking at numbers I can assure you that effect has been established very clearly. And it has nothing to do with placebo, only the second medication was the one that worked - it did more in three days than the first one after months on the highest dose. These studies sound to me like the attempts to find out whether life exists on a planet by analyzing some light spectrum through a telescope. I am sure they are useful but they seem a bit blind to what's actually going on in real life.
- NickM 2y ago
  Keep in mind that studies find a strong effect for placebos: the numbers are not saying "these pills do nothing" they're saying "these pills seem to do a lot, but placebos do almost as much". Obviously the effect feels extremely real to you, but we wouldn't see a strong placebo effect in the numbers if people on placebos didn't genuinely feel much better. I get that it feels like the second drug worked much better, but expectancy effects and internal narratives are extremely strong, and they're impossible to untangle at the level of an individual.

zero_shift 2y ago

But are they better than e.g. tricyclics, MAOIs? Placebo comparisons aren't very informative for patients when there are other existing drugs.