[HN Gopher] The serotonin theory of depression: a systematic rev...
___________________________________________________________________
The serotonin theory of depression: a systematic review of the
evidence (2022)
Author : flaxxen
Score : 72 points
Date : 2025-02-27 18:27 UTC (1 days ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| Aurornis wrote:
| Important to note that the serotonin theory of depression doesn't
| have to be strictly true for SSRIs to be effective. People who
| having passing familiarity with neuroscience often assume that
| psychiatric medications work by correcting deficiencies, but this
| isn't true. It's also not accurate to say that SSRIs "give you
| more serotonin" or any of the other variations on that theme.
|
| Neurotransmitters aren't simple levels in the brain that go up
| and down, despite how much podcasters and fitness influencers
| talk about them like that. Neurotransmitter dynamics are complex
| and the long-term adaptations after taking medications like an
| SSRI can't be simply described in terms of "levels" going up and
| down. There are changes in frequency, duration, and movement of
| Serotonin across synapses that are much more complex. There are
| also adaptations to the receptors, including auto-receptors which
| modulate release of neurotransmitters (side note: some newer
| antidepressants also directly target those autoreceptors with
| possibly slight improvements in side effect profile).
|
| So keep that in mind when reading anything about the serotonin
| theory of depression. This is often brought up as a strawman
| argument to attack SSRIs, but we've known for decades that the
| serotonin theory of depression never fully explained the
| situation. We've also known that some conditions like anxiety
| disorders are associated with increased serotonin activity in
| parts of the brain, which SSRIs can normalize.
| kittikitti wrote:
| You should keep in mind that it's a serotonin hypothesis of
| depression, as noted in the article. Calling it a theory is
| unsupported by the science.
| Aurornis wrote:
| The title of the paper is "The serotonin theory of
| depression" and it uses the phrase throughout the paper.
| kittikitti wrote:
| Can you tell me where it referenced it as a theory outside
| of the headline? It also concluded that there is a lack of
| evidence for the association so why would the authors call
| it a theory?
| Aurornis wrote:
| Use your browser's search function. At least 4 instances
| throughout the article
|
| > It also concluded that there is a lack of evidence for
| the association so why would the authors call it a
| theory?
|
| Read the article. It explains this in the introduction.
| Click some of the citations.
| kittikitti wrote:
| "The main areas of serotonin research provide no
| consistent evidence of there being an association between
| serotonin and depression, and no support for the
| hypothesis that depression is caused by lowered serotonin
| activity or concentrations."
|
| I wouldn't call it a theory especially if you're being
| semantic about serotonin reuptuke. Perhaps it's you who
| is using words you don't understand?
| aeturnum wrote:
| Exactly this - SSRI's efficacy was established based on
| improvements in reports from depressed people and we formed a
| theory about the mechanism based on the interactions we
| understood. As we try to prove that theory out it turns out our
| theories don't hold - but people who are depressed still
| improve when on SSRIs! So we're still working on the mechanism
| (which we always knew was incomplete at best) but this work
| isn't about the underlying efficacy of the drugs on the
| condition. It's about the nerdy explanation for why SSRIs work.
| thomassmith65 wrote:
| but people who are depressed still improve when on SSRIs
|
| Does that mean 'over 50%' of them improve, or is it, as is
| more common with pharmaceuticals, closer to a rounding error?
|
| There was a deluge of media a couple decades ago about Prozac
| and its dramatic effects.
|
| A few years later, I read some report that the studies
| testing its efficacy had ambiguous conclusions.
| Aurornis wrote:
| > Does that mean 'over 50%' of them improve, or is it, as
| is more common with pharmaceuticals, closer to a rounding
| error?
|
| This question is more complicated than it appears.
|
| One of the biggest challenges with depression studies is
| that the placebo group always improves dramatically, too.
| Using your terms, "over 50%" of the placebo group would
| likely show improvements in their depression inventories.
|
| This makes it very complicated to interpret the studies,
| because now you have to look for how much more the active
| treatment group improves relative to the placebo group.
|
| This is a huge detail that gets abused a lot by anti-pharma
| people, who write headlines about how SSRIs are "barely
| better than placebo" and then ignore the actual statistics.
| Another common tactic is to try to reframe the thresholds
| in different terms like "effect size" and then pool studies
| together to try to show that the "effect size" is below
| some arbitrary threshold.
|
| Another challenge is that placebo response has been getting
| stronger over the years and nobody really knows why. Some
| antidepressant studies have even been halted because,
| ironically, the placebo group improved so much that there
| numerically wasn't much room left for the active group to
| be statistically better given the sample size. This is less
| of a problem with very large scale studies where smaller
| margins can be shown to be more statistically significant,
| but those are expensive and rare.
|
| There isn't really a question about whether or not they are
| effective for many patients in the world of empirical
| treatment. However, if you go digging through the internet
| you can find plenty of commentary trying to convince you
| they don't work. Sadly, I've had some close friends and
| family members delay SSRI treatment for years because they
| read too many of these studies, but when they finally gave
| in and did a trial it turned their life around. The drugs
| aren't perfect and don't work for every situation, but they
| do work for a lot of people.
| nostrebored wrote:
| Can you explain why low percentage improvement over
| placebo is not important?
| Aurornis wrote:
| Imagine you have a depression inventory (test) with 21
| questions, rated from 0-3. The highest score is 3 * 21 =
| 63 indicating the most severe depression. The lowest
| score is 0, indicating no depressive symptoms at all.
|
| In practice, the average person will fall more in the
| range of maybe 5-15 due to vague symptoms like "I don't
| sleep as well as I used to" triggering some of the
| points. The average depressed person who seeks treatment
| might fall in the range of 25-35.
|
| Now imagine the placebo group goes in with an average
| score of 35 and improves to a score of 25 by the end of
| the test. The SSRI group improves to an average of 20 by
| the end of the test. Is this significant? Well, it
| depends on how many patients you have in the sample size.
|
| That's the problem. There's only so much room in these
| scales for improvement, so when both groups improve a lot
| you need to have a larger sample size to get statistical
| significance. Getting a lot of patients in a study
| (hundreds) is very expensive, so it's only a small number
| of studies that can pull this off.
| nostrebored wrote:
| Right, but study power is really the responsibility of a
| pharma company. It's not like this is some new and novel
| medication, it's been used for decades and has been
| questionable for _literally the entirety of the time_.
| ants_everywhere wrote:
| The problem with being barely measurably better than a
| placebo is that each study is a coin flip whether it
| supports your drug or not. And you can just file drawer
| any study that didn't go your way (as happens with the
| majority of null results).
|
| So the published results are over-sampling studies where
| the statistics happened to work and under-sampling
| studies where they didn't.
| arcticbull wrote:
| 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/
|
| [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC4592645/
| Aurornis wrote:
| > 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
|
| There's a lot of misinformed fear mongering in your
| comment.
| treis wrote:
| >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 wrote:
| Marginally better means they do, in fact, outperform.
| mike_ivanov wrote:
| Now do the same outside of the clinical conditions, in
| the patients' natural environment -- and compare the
| results.
| specialist wrote:
| There's 3 choices. Both placebos and SSRI perform better
| than doing _nothing_.
| bluescrn wrote:
| > 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 wrote:
| 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.
| Blackthorn wrote:
| > SSRIs aren't shown to be much better than placebo
|
| Or in other words: it's better than placebo.
| cess11 wrote:
| How did you determine that the side and negative social
| effects aren't large enough to outweigh that difference?
| Mistletoe wrote:
| 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://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 wrote:
| https://www.astralcodexten.com/p/all-medications-are-
| insigni...
| NickM wrote:
| 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.1142338
| 190
| crdrost wrote:
| > 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
| alpaca128 wrote:
| > 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.
| aeturnum wrote:
| > _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.
| alpaca128 wrote:
| 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 wrote:
| 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 wrote:
| 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?
| dondraper36 wrote:
| A fairly surprising fact revealing how little we understand the
| efficiency of SSRIs is that the serotonin level rises pretty
| quickly once you have started taking an SSRI.
|
| Still, there is an unexplained cascade of reactions that takes
| weeks before patients notice any improvement.
|
| As much as I respect proof-based medicine, the very fact that
| scientists can't explain how all this works made me want to
| stop my treatment and just do more weightlifting and running.
| TZubiri wrote:
| >how little we understand the efficiency of SSRIs
|
| A drug that is taken by millions of people, if your take is
| that we understand it too little, either you are deep enough
| in the subject to make some interest questions, or you are
| missing the forest for the trees.
|
| I'm not sure how useful it is to keep investigating exactly
| how it works on a chemical level, yeah for sure some people
| should look into it, but in the same way that some one should
| do 1600m in the regional competition of Minnesotta, as a
| niche.
|
| You can observe the effects of the medication on people,
| done.
|
| I remember seeing a video on a cannabis researcher explaining
| that they didn't find any difference between the indica and
| sativa strains for example, and she talked about chemical
| properties. Just get 10 people to smoke one or the other and
| you are done.
|
| There is such a thing as overintellectualizing, and FUTON
| bias isn't a particularly impressive way to do it.
| swores wrote:
| > _" I'm not sure how useful it is to keep investigating
| exactly how it works on a chemical level"_
|
| It has the potential to be incredibly useful.
|
| Not because there's a benefit to being able to tell
| patients "this is the technical explanation of how the SSRI
| we're giving you will help", but because we currently don't
| have a perfect treatment for depression, and understanding
| how existing imperfect (but useful) treatments actually
| work might lead to either creating better SSRIs that are
| more effective, or to creating non-SSRI treatments that we
| haven't yet thought of.
| Aurornis wrote:
| There's actually far more research into what happens after
| starting an SSRI than you're implying. We know, for example,
| that certain downstream adaptations takes weeks to fully
| appear. We also know that the initial increase in serotonin
| concentrations is limited by 5-HT1A negative feedback, but
| 5-HT1A downregulates over time and allows the synaptic
| concentrations to increase again.
|
| > the very fact that scientists can't explain how all this
| works made me want to stop my treatment and just do more
| weightlifting and running
|
| Weightlifting and running are complimentary, not
| substitutive. Most people can't simply replace a powerful
| medication with _more_ running and weightlifting.
|
| You might also be surprised at how many modern medications
| operate on partial theories. There's not actually anything
| wrong with that. There are a lot of medications that
| hypothetically should work based on scientific understanding
| of the brain but don't seem to show efficacy in studies.
|
| It's more important that we validate the safety profile and
| efficacy in real-world testing.
| dondraper36 wrote:
| I am not saying that quitting SSRIs is the ultimate answer,
| it just works (sort of) for me mostly because I am not that
| depressed.
|
| Also, having partial theories is not wrong, but in the case
| of SSRIs, I deliberately chose to avoid medications that I
| can do without (again, this is highly subjective).
|
| Another concern of mine is that there are now warnings for
| some popular SSRIs that ED symptoms in men might be
| permanent.
| scns wrote:
| > Another concern of mine is that there are now warnings
| for some popular SSRIs that ED symptoms in men might be
| permanent.
|
| They are for some of the unlucky 10%. Buspirone might
| help.
| TZubiri wrote:
| It sounds like a very naive explanation of depression. I'm
| cynical enough to believe that's why it's popular:
|
| "You are sad because you are missing happy chemicals"
|
| Reality is more complex, hitchen's razor tells us we don't need
| to spend more time down that road.
|
| That said, I'm open to the idea that ssri's (while certainly
| tangential to the theory) are more complex. If only because
| they may be prescribed early on either due to a physician
| desire for a simple theory or due to the patient's desire for
| it. But once you have gone down that road you can't change
| course easily.
|
| I believe whatever issue existed prior to SSRI onset becomes
| secondary (whether for better or worse) to the symptomps caused
| by SSRIs themselves, the patient becomes fungible and the
| disease a categorizable syndrome with clear treatment and
| support systems (and low suicide rates, which is usually the
| concern of family).
|
| On that note, the medication is not only taken for the patient,
| but some properties are designed/selected for the physician
| (low suicide/malpractice rates) and family (less outwardly
| symptons). In this way it's a milder version of lobotomies to
| my judgement.
|
| End rant
| 42772827 wrote:
| > People who having passing familiarity with neuroscience often
| assume that psychiatric medications work by correcting
| deficiencies, but this isn't true.
|
| They think this because that's literally what the commercial
| for Zoloft said. [0]
|
| [0] https://youtu.be/twhvtzd6gXA
| agumonkey wrote:
| What I'm trying to figure out is the interplay between the
| transmitters, and "semantic" (sorry, making this term up, not a
| neurologist, basically your representation of the world) layers
| in the brain. What interpretation mechanism are affected by
| brain state to distort your perception of so many things.
| Lerc wrote:
| I think if it like a snow globe, occasionally the snow falls
| into patterns you don't like, there is an abundant body of
| science that covers principles of physics that dictate how the
| snow moves. You might be able to come up with some broad
| patterns that show what lead to outcomes that you don't want.
|
| Nevertheless the best option for fixing the undesirable pattern
| of snow is to give the globe a quick shake. Solutions do not
| necessarily require a complete understanding of the problem, or
| even directly target the problem.
|
| Now if you only wanted to move a few problematic flakes without
| shifting any others, that's a different, much harder problem.
| TwoPhonesOneKid wrote:
| All of this fine, but surely in your context the efficacy of
| SSRIs should not imply the accuracy of a serotonin theory of
| depression. At best we know that the medication works, at worst
| we know that it's actively encouraging people to kill
| themselves, although the latter seems a little unlikely atp.
|
| Having been on an SSRI myself I gave up on the hope of SSRIs
| forming the basis of real treatment decades ago. Bupropion
| seems less harmful but also seems to have similarly small
| impact.
| H8crilA wrote:
| Psychiatric benefits of SSRIs show around 2 to 4 weeks after
| the therapy starts, but the serotonin levels increase on the
| first day. It is obvious that depression is not just some
| "nutritional" problem in the synapses. It does look like it can
| be cured by systematic "overeating", though, at least in
| some/many cases.
| debacle wrote:
| For anyone interested in their own depression, some anecdotal,
| unscientific non-medical advice that I received from HN about a
| year ago:
|
| 5-HTP is a serotonin precursor that you can take in low doses to
| help do a lot of different things. For me, it lowered food
| cravings and impulsiveness, balanced out sleeping anxiety, vastly
| improved my gut health, and really helped with my depression. I
| have a positive mood about me that I haven't had since I was a
| teenager, and I am so vastly enjoying life today, despite the
| trials. Before starting a daily regimen of 5-HTP, I was worried
| that I might one day lose myself to suicide. Now I treasure every
| day. Truly changed my life. Maybe it will change yours.
|
| Again this is completely anecdotal, unscientific non-medical
| advice.
| felizuno wrote:
| I have also had huge results with 5-HTP (in combination with
| vitamin D). I had that breakthrough in 2017 and it has been a
| consistent improvement ever since so I feel comfortable
| suggesting it. I have more recently had a similar "OMFG" moment
| with supplementing creatine but I'm only a few months into that
| so not ready to make claims about durability. I was diagnosed
| with chronic depression as a child (in 1994) and have taken
| Wellbutrin, Prozac, Lexapro, and Celexa at different points in
| my life. Personally I never experienced benefits that
| outweighed the side effects with any of those drugs. Taking an
| approach that centers on whole-body (and really specifically
| intestinal) serotonin has made the biggest difference in my
| life. Avoiding processed carbohydrates like pasta and bread has
| also been a piece of the puzzle, but unequivocally 5-HTP + VitD
| has been the standout difference maker.
| Imanari wrote:
| How much do you take? Just standard stuff from amazon?
| debacle wrote:
| I take the lowest dose (200mg/mcg?) from Amazon.
| BiteCode_dev wrote:
| What does are you taking? Do you need to ramp it up or cycle
| it? What's your source? Anything else important to know?
| xlbuttplug2 wrote:
| Just a reminder not to impulse buy without first doing some
| research. IIRC serotonin syndrome is a risk, especially if
| already on antidepressants.
|
| Some things to note in case you decide to go ahead anyway:
| https://www.reddit.com/r/Nootropics/comments/28489u/comment/...
| johnisgood wrote:
| Serotonin syndrome is a low risk, I believe. If it is as
| common as they make it out to be, I should have had it a
| million times, unless I am somehow the exception.
| usednet wrote:
| This was a seminal review in psychiatry that I am fully in
| agreement with but there are a lot of easy to draw conclusions
| from this review that are false.
|
| SRRI efficacy for one - The nature of SSRIs is that they are
| highly effective for some patients and useless/detrimental to
| others. This does not lend itself well to traditional measures of
| effect size. For those in the comments pointing out SSRIs low
| effect size, note that the effect size of morphine for pain is
| only 0.4 (SSRIs score 0.3). For instance, drugs that
| significantly improve 60-100% of patients are clinically
| insignificant under various guidelines. I can expound upon the
| various methodological reasons this is the case if there is
| interest.
|
| This is not to say that SSRIs are good. There is no doubt they
| are overprescribed, have underdiscussed side effects, and are
| barely understood by their prescribers. I was severely depressed
| with suicidal ideation since I was 6 years old until I was young
| adult. I have pored over the psychiatric scientific literature
| for many years now, and I will say that understanding the
| sociological reasons for depression was much more effective at
| helping me than learning about the biological or pharmacological
| aspects. If you are in a similar position, I cannot recommend
| enough reading Crazy Like Us: The Globalization of the American
| Psyche by Ethan Watters as a starting point.
| 6stringmerc wrote:
| Thank you for ending with a further reading suggestion as a
| useful complement to your personal experience and research.
| Your write up is a strong positive in continuing toward
| advancing education, open mindedness, and patience with a
| delicate subject. I appreciate your notes in this context and,
| as small as one voice is in "anecdata" context, I'm glad to see
| the mention of sociological factors because it's also in my
| journey of discovering more.
| ieie3366 wrote:
| Having taken SSRI for anxiety, it feels more like a second order
| effect. The brain is anxious, the serotonin goes in, the
| serotonin is not exactly "anti-anxiety" signal but "feel-good"
| signal.
|
| Repeat constantly every day for months and the brain thinks, "ok
| we constantly have this euphoria going on, time to turn the
| anxiety off no need for it anymore"
|
| This would also be why the serotonin increase is instant when
| starting SSRIs, but anti-anxiety effects take months and are
| gradual
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