| ▲ | Paracompact 11 hours 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. |
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| ▲ | Rendello 11 hours ago | parent | next [-] |
| 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 |
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| ▲ | Otterly99 2 hours ago | parent | next [-] | | Thanks for the paper, it is actually quite crazy to think about when SSRI are basically the standard to treat depression. I recently read a book about "The brain energy theory of mental illnesses"[1] which encapsulates depression and found it pretty compelling. It seems to be a relatively new and active area of research[2], so there is hope! [1]: https://books.google.fr/books/about/Brain_Energy.html?id=GIx...
[2]: https://pubmed.ncbi.nlm.nih.gov/38183680/ | |
| ▲ | zdragnar 11 hours ago | parent | prev | next [-] | | 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-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. | | |
| ▲ | pcrh 2 hours ago | parent | next [-] | | Here are a few additional reports: >1. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. Conclusions: SSRIs might have statistically significant effects on depressive symptoms, but *all trials were at high risk of bias and the clinical significance seems questionable*. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects. >2. The trouble with antidepressants: why the evidence overplays benefits
and underplays risks. Widespread prescribing has not reduced mental disability or suicide, raising questions about the assessment of evidence on effectiveness and safety of antidepressants >3. In search of a dose–response relationship in SSRIs—a systematic review, meta-analysis, and network meta-analysis. Conclusions: There is no conclusive level I or level II evidence of a clinically meaningful dose–response relationship of SSRIs as a group or of single substances. High SSRI doses are not recommended as routine treatment. >4 The serotonin theory of depression: a systematic umbrella review of the evidence "We did not identify *any* trials using ‘active placebo’ or ‘no intervention’ as control interventions. " [1] https://pubmed.ncbi.nlm.nih.gov/28178949/ [2] https://www.bmj.com/content/370/bmj.m3200 [3] https://pubmed.ncbi.nlm.nih.gov/32970827/ [4] https://pubmed.ncbi.nlm.nih.gov/35854107/ | |
| ▲ | D-Machine 11 hours ago | parent | prev [-] | | The idea that simple serotonin deficiency is the whole entirety of all depressions is 100% discredited and completely incoherent in the face of current evidence, but yes, for sure it remains clear and plausible that some forms or aspects of depression involve a serotonin deficiency. However, tianeptine is serotonin reuptake enhancer and also can help with depression, so any simple deficiency hypothesis also doesn't look good either. Broadly, the "chemical imbalance" theory, left vague and unspecified, is still basically sane (though not specific enough to be super useful). |
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| ▲ | sneezychl 11 hours ago | parent | prev [-] | | The "chemical imbalance" theory is objectively wrong, but still useful in that it conveys the fact that mental disorders have physical causes. It's a purposeful simplification. | | |
| ▲ | Rendello 8 hours ago | parent [-] | | Many people take SSRIs and other medications because they believe the serotonin imbalance theory to be the modern scientific consensus. A doctor would be fired and ostracized for using the four humours, but can prescribe life-altering medication after five minutes to correct chemical imbalance, a theory which has never had much support within the scientific community. Indeed, a rebuttal [1] to that paper starts with: > Moncrieff et al. report in a review of reviews that depression is not generally linked with serotonin deficiency. This is hardly news to neuropharmacologists, which Moncrieff et al. tacitly admits, as they justify their review by citing examples of laity and general practitioners believing depression is caused by a “chemical imbalance”, i.e., in serotonin. For instance, already in 1986 did Depue and Spoont point out that serotonin deficiency may not be a general cause of depression or other psychiatric illness. Further, that increasing extracellular serotonin—e.g., with selective serotonin reuptake inhibitors (SSRIs)—treats depression does not mean decreased serotonin causes depression. I have a lot of trust in the science of medicine, but almost none in healthcare. It seems like the research is totally divorced from the medieval treatments I see doctors give all the time. "This is hardly news to neuropharmacologists" vs "laity and general practitioners believe ..." indeed. 1. https://www.nature.com/articles/s41380-023-02090-3 | | |
| ▲ | simiones 2 hours ago | parent [-] | | Note that it's not uncommon for even more widely prescribed medication to have no firmly established mechanism of action. Acetaminophen/paracetamol is probably the best example. Ultimately medication is prescribed based on evidence from clinical trials, whether or not the mechanism of action is fully understood. SSRIs work to help with depression in clinical trials when compared to placebo, so they get prescribed. |
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| ▲ | D-Machine 11 hours ago | parent | prev | next [-] |
| 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. |
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| ▲ | zer00eyz 11 hours ago | parent | prev [-] |
| 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". |
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