5 ms·

So...why do SSRI users self-report efficacy?

by Arubis 4y ago

BrianOnHN 4y ago
Correlation isn't causation. The serotonin effect may be a symptom of the depression. Treating symptoms is sufficient intervention for many.
carabiner 4y ago
https://en.wikipedia.org/wiki/Placebo https://en.wikipedia.org/wiki/Placebo
- kennywinker 4y ago
  When they test drugs, they test them against a placebo.
  - hackerlight 4y ago
    Yes, but according to Irving Kirsch, the benefit of anti-depressants above placebo is very small for anyone who isn't severely depressed, and the observed small effects can plausibly be explained by patients unblinding themselves (due to the presence of other side effects in the treatment group), or by things like publication bias. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/
    - deleted 4y ago
      [deleted]
    - rando14775 4y ago
      I'll add that side effects alone can influence depression scores. Any medication that de- or increases sleepyness will change the score of any questionaire when taken at the appropriate time of day.
  - deleted 4y ago
    [deleted]
- copperx 4y ago
  In my case, at this very moment, I'm going through antidepressant withdrawal and have random crying spells. Sure, depression might not be mediated by serotonin, but these drugs have an effect on mood. It might be that there's a different mechanism of action.
nvrspyx 4y ago
My guess, without digging into the study itself since I'm on mobile, is that there is no singular cause for depression. Rather, depression is simply a symptom of a wide range of causes, with one possible cause being low serotonin (or a reduced sensitivity to it). Or even, low serotonin is a symptom of the depression. Not all patients with depression find relief from SSRIs, or medications in general, but some certainly do.
- patmorgan23 4y ago
  It could even be that increasing serotonin is helps improve the patients mood and break thought patterns/cycles than kept them in their depression.
  - lumost 4y ago
    It could be that any forced cognitive pattern change would have the same effect. Double blind trials are hard, double blind comparative trials are more or less impossible.
  - klodolph 4y ago
    The mechanism of SSRIs is not well-described as "increase serotonin".
simonsarris 4y ago
If we don't understand the mechanism of action it can still cause an effect. After all SSRIs certainly cause plenty of other side effects.
raphlinus 4y ago
It might be a different mechanism, like brain-derived neurotrophic factor[1]. [1]: https://www.science.org/content/blog-post/how-antidepressants-work-last https://www.science.org/content/blog-post/how-antidepressant...
- deleted 4y ago
  [deleted]
PragmaticPulp 4y ago
Because psychiatric drugs don't necessarily work by counteracting specific deficits in the brain. That's a myth driven by unfortunate marketing campaigns and surface-level misunderstandings of the science. This makes intuitive sense to people when discussing other topics. For example, when someone is in pain they don't need to have an "endogenous opioid deficiency" for opioid painkillers to alleviate their pain. They're just in pain, and modulating the opioid system with drugs is one way we can reduce that pain. Or COX-2 inhibitors. Or a number of other substances. Likewise, modulating the serotonin system with SSRIs is one way we can modulate depression symptoms. People don't need to have a "serotonin deficiency" to see benefits from modulating their serotonin system.
biophysboy 4y ago
Depression has no common cause or common set of symptoms. I read a paper that likened it to a watershed, with tributaries feeding into a general pool of malaise. The watershed varies from person to person, and affects their internal “ecosystem” differently. Maybe it’s a bit cute, but with this understanding, I think the headline is not shocking. We will never find the one cause of depression because there isn’t one. In my opinion, our best bet is more personalized medicine: helping people identify which rivers are filling up their lake of depression. For most people it will be a weighted combination of many things, but I think there will usually be some principal components.
- frazbin 4y ago
  The test to see how depressed a lab mouse is, is to put it in a bucket of water and see how long it struggles. True story.
  - kortex 4y ago
    One of them is, yes. There are several, and basically all of them are some variant of "how resistant to giving into despair are you? (as a rat)". Forced swim, tail suspension, light/dark exploration activity. Kinda dark, but this research saves lives, and depression is notoriously hard to study objectively.
WalterSear 4y ago
> ...two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. > ...A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. > These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/
JaceLightning 4y ago
It's mostly a placebo https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299662/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299662/

So...why do SSRI users self-report efficacy?

by Arubis 4y ago

So...why do SSRI users self-report efficacy?

Correlation isn't causation. The serotonin effect may be a symptom of the depression. Treating symptoms is sufficient intervention for many.

carabiner 4y ago

https://en.wikipedia.org/wiki/Placebo https://en.wikipedia.org/wiki/Placebo

kennywinker 4y ago
When they test drugs, they test them against a placebo.
- hackerlight 4y ago
  Yes, but according to Irving Kirsch, the benefit of anti-depressants above placebo is very small for anyone who isn't severely depressed, and the observed small effects can plausibly be explained by patients unblinding themselves (due to the presence of other side effects in the treatment group), or by things like publication bias. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/
  - deleted 4y ago
    [deleted]
  - rando14775 4y ago
    I'll add that side effects alone can influence depression scores. Any medication that de- or increases sleepyness will change the score of any questionaire when taken at the appropriate time of day.
- deleted 4y ago
  [deleted]
copperx 4y ago
In my case, at this very moment, I'm going through antidepressant withdrawal and have random crying spells. Sure, depression might not be mediated by serotonin, but these drugs have an effect on mood. It might be that there's a different mechanism of action.

nvrspyx 4y ago

My guess, without digging into the study itself since I'm on mobile, is that there is no singular cause for depression. Rather, depression is simply a symptom of a wide range of causes, with one possible cause being low serotonin (or a reduced sensitivity to it). Or even, low serotonin is a symptom of the depression. Not all patients with depression find relief from SSRIs, or medications in general, but some certainly do.

patmorgan23 4y ago
It could even be that increasing serotonin is helps improve the patients mood and break thought patterns/cycles than kept them in their depression.
- lumost 4y ago
  It could be that any forced cognitive pattern change would have the same effect. Double blind trials are hard, double blind comparative trials are more or less impossible.
- klodolph 4y ago
  The mechanism of SSRIs is not well-described as "increase serotonin".

simonsarris 4y ago

If we don't understand the mechanism of action it can still cause an effect. After all SSRIs certainly cause plenty of other side effects.

raphlinus 4y ago

It might be a different mechanism, like brain-derived neurotrophic factor[1]. [1]: https://www.science.org/content/blog-post/how-antidepressants-work-last https://www.science.org/content/blog-post/how-antidepressant...

deleted 4y ago
[deleted]

PragmaticPulp 4y ago

Because psychiatric drugs don't necessarily work by counteracting specific deficits in the brain. That's a myth driven by unfortunate marketing campaigns and surface-level misunderstandings of the science. This makes intuitive sense to people when discussing other topics. For example, when someone is in pain they don't need to have an "endogenous opioid deficiency" for opioid painkillers to alleviate their pain. They're just in pain, and modulating the opioid system with drugs is one way we can reduce that pain. Or COX-2 inhibitors. Or a number of other substances. Likewise, modulating the serotonin system with SSRIs is one way we can modulate depression symptoms. People don't need to have a "serotonin deficiency" to see benefits from modulating their serotonin system.

biophysboy 4y ago

Depression has no common cause or common set of symptoms. I read a paper that likened it to a watershed, with tributaries feeding into a general pool of malaise. The watershed varies from person to person, and affects their internal “ecosystem” differently. Maybe it’s a bit cute, but with this understanding, I think the headline is not shocking. We will never find the one cause of depression because there isn’t one. In my opinion, our best bet is more personalized medicine: helping people identify which rivers are filling up their lake of depression. For most people it will be a weighted combination of many things, but I think there will usually be some principal components.

frazbin 4y ago
The test to see how depressed a lab mouse is, is to put it in a bucket of water and see how long it struggles. True story.
- kortex 4y ago
  One of them is, yes. There are several, and basically all of them are some variant of "how resistant to giving into despair are you? (as a rat)". Forced swim, tail suspension, light/dark exploration activity. Kinda dark, but this research saves lives, and depression is notoriously hard to study objectively.

WalterSear 4y ago

> ...two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. > ...A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. > These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/

JaceLightning 4y ago

It's mostly a placebo https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299662/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299662/