[HN Gopher] "No convincing evidence" that depression is caused b...
       ___________________________________________________________________
        
       "No convincing evidence" that depression is caused by low serotonin
       levels
        
       Author : mellosouls
       Score  : 437 points
       Date   : 2022-07-20 02:39 UTC (20 hours ago)
        
 (HTM) web link (www.bmj.com)
 (TXT) w3m dump (www.bmj.com)
        
       | ornornor wrote:
       | When you look into the studies for antidepressants, the track
       | record is abysmal.
       | 
       | They're not innocuous, trigger serious side effects, some are
       | hard to quit, but more importantly they only make a difference in
       | people with extremely severe depression.
       | 
       | And doctors often downplay or don't mention side effects honestly
       | because they don't want patients to not take them.
       | 
       | The studies justifying antidepressants as effective to the FDA
       | are disturbingly flawed: people who were not responsive were
       | excluded from the studies...
       | 
       | Anyway, I found this website very enlightening on the topic:
       | https://www.theinnercompass.org/learn-unlearn/intervention/a...
       | along with several Reddit threads from peoples experience with
       | various antidepressants.
       | 
       | This is not medical advice and there are cases where
       | antidepressants are necessary and make a difference. But if you
       | have anything else than extreme depression and no other mental
       | health conditions (schizophrenia etc), consider magic mushroomed:
       | a few intentional trips can do wonders to see what's troubling
       | you from a different angle and help you move forward.
        
         | can16358p wrote:
         | Any links to the Reddit threads if handy? I'm interested for
         | personal issues and Reddit always comes much more useful than
         | actual psychiatry in my case (not sarcasm, I frankly mean it).
        
           | ornornor wrote:
           | I used "site:Reddit.com antidepressants" or with specific
           | medicine names. Use ddg for that because the site: thing
           | hasn't worked on google in years and you'll get poor results.
        
         | raducu wrote:
         | The track record is not abysmal:
         | https://slatestarcodex.com/2014/07/07/ssris-much-more-than-y...
        
           | ornornor wrote:
           | > more importantly they only make a difference in people with
           | extremely severe depression
           | 
           | Which your link confirms. And your link also states that
           | antidepressants were oversold, especially to people with mild
           | depression, a level for which antidepressants aren't
           | particularly good at treating especially in light of the side
           | effects and difficulty to quit.
        
         | PraetorianGourd wrote:
         | Yeah an unregulated and uncontrolled consumption of a poorly
         | dosed hallucinogenic is totally better than a double-blind
         | study of SSRI/SNRI.
         | 
         | I swear, I do not reject the possibility that hallucinogenics
         | can cure depression better than existing meds, but the almost
         | religious enthusiasm for such a poorly studied chemical is
         | deeply concerning.
         | 
         | And yes, before you accuse me of being a pharma shill, I know
         | that the lack of serious study is due to legal restrictions and
         | not scientific evidence. But that doesn't change the fact that
         | they've not been studied rigorously. In my State, they are
         | being actively studied, let us hold back the praise until the
         | results are in.
        
           | hirvi74 wrote:
           | It's almost a self-fulfilling prophecy. If anti-depressants
           | were so effective, people wouldn't be flocking to
           | psychedelics for treatment.
           | 
           | Stimulants are the most useful medication we have found for
           | ADHD. Without access to them, what do people with ADHD flock
           | to? Caffeine, Nicotine, Alcohol, Cannabis, etc. Substances
           | that are stimulants or can have stimulating effects.
           | 
           | I am no woo-woo person, but perhaps our bodies when flocking
           | to something are trying to tell us something? Alcohol also
           | works great for anxiety (and super dangerous), so we created
           | benzos in alcohol's image (though I think benzos can be just
           | as dangerous for some).
        
           | LatteLazy wrote:
           | Careful: whether SSRIs and SNRIs work is unrelated to whether
           | hallucinogenics do or don't. hallucinogenics being shit
           | doesn't make SSRI/SNRIs a good bet.
           | 
           | Also, those exact studies you refer to show that SNRIs work
           | very poorly and are very limited.
           | 
           | Usually studies have fewer than 100 participants:
           | 
           | * people are dropped from the study arbitrarily
           | 
           | * they are not double blind
           | 
           | * they are not representative of the population
           | (overwhelmingly participants are white, male, well off or
           | young with no other health complaints and few serious
           | problems)
           | 
           | * studies are usually very short (<100 days) for medicines
           | that are prescribed for years
           | 
           | They then find drugs are less than 15%ppts more effective
           | than placebos. In exchange you get quite extreme side effects
           | for a significant number of users from impotence to
           | suicide...
           | 
           | The lancet picked this up and did. meta-study. Their
           | conclusions:
           | 
           | >We identified 28 552 citations and of these included 522
           | trials comprising 116 477 participants. In terms of efficacy,
           | all antidepressants were more effective than placebo, with
           | ORs ranging between 2*13 (95% credible interval [CrI]
           | 1*89-2*41) for amitriptyline and 1*37 (1*16-1*63) for
           | reboxetine. For acceptability, only agomelatine (OR 0*84, 95%
           | CrI 0*72-0*97) and fluoxetine (0*88, 0*80-0*96) were
           | associated with fewer dropouts than placebo, whereas
           | clomipramine was worse than placebo (1*30, 1*01-1*68). When
           | all trials were considered, differences in ORs between
           | antidepressants ranged from 1*15 to 1*55 for efficacy and
           | from 0*64 to 0*83 for acceptability, with wide CrIs on most
           | of the comparative analyses. In head-to-head studies,
           | agomelatine, amitriptyline, escitalopram, mirtazapine,
           | paroxetine, venlafaxine, and vortioxetine were more effective
           | than other antidepressants (range of ORs 1*19-1*96), whereas
           | fluoxetine, fluvoxamine, reboxetine, and trazodone were the
           | least efficacious drugs (0*51-0*84). For acceptability,
           | agomelatine, citalopram, escitalopram, fluoxetine,
           | sertraline, and vortioxetine were more tolerable than other
           | antidepressants (range of ORs 0*43-0*77), whereas
           | amitriptyline, clomipramine, duloxetine, fluvoxamine,
           | reboxetine, trazodone, and venlafaxine had the highest
           | dropout rates (1*30-2*32). 46 (9%) of 522 trials were rated
           | as high risk of bias, 380 (73%) trials as moderate, and 96
           | (18%) as low; and the certainty of evidence was moderate to
           | very low.
           | 
           | https://www.thelancet.com/journals/lancet/article/PIIS0140-6.
           | ..
           | 
           | I think even assuming good faith for all those studies, those
           | are poor results when you include the low acceptability. If
           | you don't assume good faith you're left wondering if these
           | drugs work at all.
           | 
           | It should go without saying that NO ONE should stop or change
           | their medication (especially highly addictive ones like
           | these) based on a HN comment. Please speak to your doctors
           | dear readers.
        
           | taurath wrote:
           | > Yeah an unregulated and uncontrolled consumption of a
           | poorly dosed hallucinogenic is totally better than a double-
           | blind study of SSRI/SNRI.
           | 
           | Frankly, it could be and we'd have no way of knowing with the
           | "rigor" we put through pharmacological stories, if your goal
           | is effectiveness.
           | 
           | That the entire field of psychology is sort of In conflict
           | over the mechanisms, validity, and treatment models of trauma
           | and dissociation, which frequently underly depression and
           | anxiety symptoms.
        
           | ornornor wrote:
           | You do you of course.
           | 
           | You can grow your own mushrooms at home fairly easily and
           | then you have more control over quality/contamination etc.
        
             | grenoire wrote:
             | Correct, in theory. However, if you are just starting out
             | growing you won't have the knowledge to assess quality or
             | control contamination.
        
             | mellavora wrote:
             | Ok, so you have some control over quality. I'll also be
             | generous and assume you have good estimate of dosages
             | and/or some way to maintain consistency of dosages (anyone
             | else reading this, the standard advice is to take less than
             | you think you want and wait 45 min or so, then take more if
             | needed to reach planned cruising altitude. This works if
             | you have enough prior experience to calibrate by, otherwise
             | is very difficult).
             | 
             | How do you know which dosage is best for treating
             | depression?
             | 
             | Assuming the best treatment is a series of sessions, how do
             | you know the optimal spacing of sessions, and the optimal
             | dosing per session?
             | 
             | You are correct that the trips should be intentional. Who
             | sets these intentions, which intentions are the most
             | helpful, how do you guide the session along the lines of
             | the intentions (recalling that the session might include
             | full ego death and conviction that both your mind and
             | reality are distinct and permanently broken) and most
             | importantly how do you structure the post-session therapy
             | to integrate the learnings and actually get some personal
             | growth out of this?
             | 
             | Are there age-related differences in this? What is the
             | protocol for a early 20s vs a mid-50s vs 70s/80?
             | 
             | Also, to look at your own advice ("if you have anything
             | else than extreme depression and no other mental health
             | conditions") how do you actively screen for this?
             | 
             | These are concerns which are well addressed within shamanic
             | circles-- so I'm not speaking with the voice of pharma
             | here.
             | 
             | Psychedelics are powerful tools. Like any other power tool,
             | they can be a great help and also fairly risky if not used
             | carefully. Insert your own woodshop analogies here.
             | 
             | And if you are going to use them anyway, without working
             | with someone who knows what they are doing, please please
             | please:
             | 
             | 1) start with small doses
             | 
             | 2) do some reading BEFORE. Minimal list: Hudson Smith,
             | "Cleansing the Doors of Perception" and James Fadiman The
             | Psychedelic Explorer's Guide: Safe, Therapeutic, and Sacred
             | Journeys
        
               | ornornor wrote:
               | Yes I kinda assumed that if someone was considering
               | giving this a shot, they'd research the subject very
               | thoroughly before to get a good understanding of the
               | effects, preparation, effects, doses, etc.
               | 
               | The genera consensus seems to be that mushrooms
               | (psilocybin) can't kill you. You can't OD on them. There
               | is no known LD50 (that's "practical" to achieve anyway),
               | they dont cause addiction, and if you take them too often
               | they actually stop having an effect until you take a
               | break and use again.
               | 
               | There are risks if you have other mental health
               | conditions like schizophrenia etc, but (according to my
               | research), the only risk if you're otherwise healthy is
               | to have a "bad trip" where you're basically experiencing
               | negative feelings. By reading about the experience, you
               | also learn that if you resist the bad trip it gets worse
               | but if you look at it with curiosity (what is my brain
               | trying to tell me?) then you'll have an easier time.
               | 
               | About assessing te severity of your depression, there is
               | a standard test (of which I forget the name) that is also
               | used in the studies submitted to the FDA for approval of
               | antidepressants that ask questions, you then add the
               | points up, and anything above a certain number is severe
               | depression. Although this is yet another flaw of the
               | studies, the people running the studies don't even agree
               | on the score that give you mild vs severe depression.
               | 
               | Again, I have no medical training so this is just a
               | random stranger's opinion on the internet. To anyone
               | reading: educate yourself about the whole thing, see if
               | you're willing to try, and make your own decisions.
        
               | bowsamic wrote:
               | There are four main risks for most people:
               | 
               | - PTSD caused by bad trip. Bad trips are not uncommon,
               | and it's not easy to let go. Part of the reason why
               | psychedelics are so effective is that they basically
               | force you to let go, otherwise you will have a bad trip.
               | But some people can't do that, I couldn't, and you can
               | end up causing long lasting psychological damage due to
               | this. I had an existential crisis and became pretty
               | suicidal for a few months after I had a couple of trips.
               | I actually had to take up a religion to cope with it. The
               | therapy services in the UK had no idea what to do to help
               | me and made me feel alienated
               | 
               | - DP/DR (depersonalisation/derealisation). Can be short
               | lasting, can be long lasting, can be flashbacks, can be
               | constant
               | 
               | - HPPD (Hallucinogen persisting perception disorder).
               | Described as anywhere between "visual snow" and "you
               | never came down from the trip". No one knows why this
               | happens or who it happens to, if it occurs differently
               | with different psychs. Many people commit suicide over
               | this one, since it can basically cause psychosis as some
               | people never stop having intense hallucinatory effects
               | for months or even years. If they can't come to terms
               | with it it can be extremely disorientating and
               | alienating. Andrew Callaghan of Channel 5 news / All Gas
               | No Brakes has this. Kind of frightening since it's most
               | trippers' worst nightmare to never come down from the
               | trip, but that's actually a thing that happens to some
               | people
               | 
               | - Flashbacks, which I would say are different to the
               | other three, in that they are a sudden return to the
               | tripping state of mind randomly, but not necessarily
               | visual or DP/DR. I think this one is the least explored
               | and least well known about
        
       | ldjkfkdsjnv wrote:
       | Too tired to type a cogent paragraph. Just that I have seen lives
       | ruined by SSRIs.
        
         | matthewmacleod wrote:
         | Haven't you also seen lives saved by them? Because I sure have.
        
         | gillytech wrote:
         | Your comment is the most sensible I hav seen so far. I have
         | seen lives utterly decimated by SSRIS. Suicides and murders
         | caused by its side effects. Violent and suicidal tendencies are
         | on the warning labels on many of these drugs.
        
         | petesergeant wrote:
         | Comments like this caused me to not try them for waaay too
         | long. Many many many lives have been positively transformed by
         | them, too
        
         | wobblykiwi wrote:
         | They have been saving mine. My anxiety has been improving
         | tremendous amounts since starting both an SSRI and therapy a
         | few months ago. Therapy came a couple months after starting an
         | SSRI, but I was already feeling a tangible improvement before
         | even starting that.
        
         | almostthrewit wrote:
         | This is a dangerous thing to spread, in my opinion. I have
         | struggled with depression and anxiety for years, but during
         | COVID it hit me like nothing I have ever experienced before. I
         | would have probably died during COVID without finding a doctor
         | to prescribe me medicine. And I don't think it would have been
         | suicide. I would have probably become dehydrated and/or starved
         | or become mal-nutritioned because it was a literal war to eat.
         | I was having to wash down food with water after chewing it
         | enough to swallow. (Note that I never had COVID, which would
         | have been impossible having barely left my house during the
         | first 9 months of 2020.) I couldn't sleep and would wake up
         | wide awake and stressed at 4-5am. I couldn't relax. Was having
         | panic attacks. It was pure and quite literal torture. My body
         | and mind was literally on fire with stress activity. I honestly
         | probably should have been hospitalized long before I finally
         | got help.
         | 
         | While not fun working through the gamut of medicines, some of
         | them finally pulled me through it all. It took almost a year to
         | fully recover with dedication to the medicine and modifications
         | of it and therapy.
         | 
         | If I didn't have a good family and primary care doctor, I
         | guarantee I would have died in some manner unless hospitalized.
         | 
         | People need to realize there is danger to their words.
         | Psychiatry is nowhere near perfect, but people are trying. It
         | is an incredibly difficult thing to understand. But I feel
         | people who speak against medicine have never truly experienced
         | deep depression or anxiety. A panic attack can hit you sitting
         | on the couch, and then by literally doing nothing, your heart
         | rate can reach 200bpm and massive amounts of hormones making
         | your chest and skin feel like it's burning, and next thing
         | you're calling an ambulance because you think you aren't
         | breathing.
        
         | padolsey wrote:
         | Too tired to type a cogent paragraph. Just that I have seen
         | lives saved by SSRIs.
        
         | throw__away7391 wrote:
         | Same here. I've seen multiple people after getting along fine
         | for years get prescribed these meds, and within two years end
         | up completely unable to function, hold a job, maintain
         | composure during a conversation (breaking down in tears or
         | becoming violently angry), cook their own food, etc. and need
         | to talk to a therapist multiple times a week.
         | 
         | I'm sure "they're doing it wrong", but these were fully
         | licensed doctors, prescribing drugs in an approved manner.
        
           | asveikau wrote:
           | Are you sure it isn't the condition that they were seeking
           | treatment for that contributed to these things?
           | 
           | I'll give an example, I read once that about 60% of people
           | with bipolar disorder are unemployed. It isn't the diagnosis
           | that does that.
           | 
           | So I just read that comment as "they sought treatment and
           | ever since they were a wreck". Seems like the causality could
           | go the other way.
        
             | mccorrinall wrote:
             | While I only had positive experiences with SSRI so far, I
             | can definitely say that substances can cause suicidal
             | thoughts. When I took xanax, I had a lot of suicidal
             | thoughts and really had to fight to not kill myself. It's
             | just like being on autopilot and having to fight against
             | autopilot who wants to crash your car into a wall.
             | 
             | I could imagine that SSRI can activate this autopilot for
             | some people and worsens their negative thoughts.
        
             | staticman2 wrote:
             | There's some very scary anecdotes out there. I saw one on
             | an obscure subreddit for people suffering from negative
             | antidepressant drug symptoms where a person said they went
             | to the hospital immediately after taking an SSRI due to an
             | adverse reaction and they have had trouble concentrating on
             | things since.
             | 
             | If the person is correct and not dusional they had a
             | statistically unlikely reaction to the drug- presumably too
             | rare to show up in the drug approval process- and it ruined
             | their life.
        
       | locusofself wrote:
       | Anecdata, but I was often depressed for most of my adjust life.
       | Around 5-6 years ago (age 33 at the time), I started taking 20mg
       | Citalopram. I have experienced almost no depression since I
       | started taking this medication, I'm far more focused and
       | productive than I have ever been. It could be a factor of age and
       | getting married as well, and just settling into my life. But my
       | depression felt like something out of my control.
        
         | cameronh90 wrote:
         | Sertraline has almost entirely fixed my panic disorder.
         | 
         | It had no obvious cause and months of therapy had no impact.
         | Within a few days of taking sertraline, it was essentially
         | cured. I still get anxious from time to time but I'm able to
         | live a completely normal life again. I had a few side effects
         | (GI especially) for a few weeks but now the only side effect I
         | have is I yawn a lot more, which is pretty tame.
         | 
         | I'm a big believer in the gut-brain connection and wonder if
         | maybe it was something to do with the drug's GI effects that
         | helped, but ultimately I have no idea and it doesn't really
         | matter.
        
           | jinder wrote:
           | You're correct - it appears to work via the gut-brain axis,
           | see my comment above.
        
         | mccorrinall wrote:
         | Same here, but with Fluoxetine (Prozac). However, I don't think
         | exactly that fluoxetine made me less depressed. It only made me
         | more ,,aggressive" and more risk taking, and the antidepressing
         | effect came from the positive results of taking such risks. I
         | just ,,don't care" about failures as much as I used to.
         | 
         | E.g. I finally started talking to girls, because I wouldn't
         | care about rejection that much. => Got into my first
         | relationship and was happy.
         | 
         | Also, I started working on my passion project full time and I
         | recently registered a company for it. Two years ago I would
         | have not thought about doing this, as working for an employer
         | is way ,,safer".
         | 
         | But I don't care about failing anymore.
        
           | MarcelOlsz wrote:
           | Shit I need pills that do the opposite lol.
        
             | CAP_NET_ADMIN wrote:
             | I have ADHD, frequently exhibited risky behaviour, ADHD
             | medication (MPH) reduced this effect for me, I'm more
             | conscious and think things through before they happen.
        
         | raducu wrote:
         | It's not just anecdotal evidence, the whole anti-antidepressant
         | hype seems to re-emerge every few years, like a plague. After
         | trying a few different anti-depressant the vast majority of
         | people do improve. And the people bashing antidepressants fail
         | to come up with any proven alternatives.
         | 
         | Is there a conspiracy shutting down depression curing
         | alternatives all around the world?
        
       | eixiepia wrote:
       | What are the views on SSRIs prescribed for OCD and anxiety? The
       | dosage for these conditions is much larger than for depression,
       | often ten times or more.
        
       | barbs wrote:
       | For good in-depth investigative journalist approach to the topic,
       | I highly recommend the book "Lost Connections" by Johaan Hari.
       | 
       | The author himself was diagnosed with depression and prescribed
       | SSRIs for the longest time. Through talking with experts and
       | understanding the roots of depression (in short, a lack of
       | connection with the world and community), he now no longer takes
       | them.
        
       | sebastianconcpt wrote:
       | And testosterone levels?
        
       | foolfoolz wrote:
       | imagine working in a field where nothing is probably true
        
         | pcrh wrote:
         | Indeed. The whole profession of psychiatry suffers from poor
         | application of scientific research, to the extent that the
         | National Institute of Mental Health once banned reference to
         | the Diagnostic and Statistical Manual of Mental Disorders
         | (known as DSM-5).
         | 
         | https://www.science.org/content/article/nimh-wont-follow-psy...
        
       | paulpauper wrote:
       | It's sorta fascinating how anti depressants work yet no one
       | really know how or why they work.
        
         | philliphaydon wrote:
         | We know how and why SSRIs work in regards to serotonin. We
         | don't understand why some people produce little or absorb
         | serotonin too quickly requiring SSRIs drugs to manage it.
        
           | mjfl wrote:
           | right because what serotonergic synapses do is they tickle
           | the other neurons to make them happier right?
        
             | philliphaydon wrote:
             | We know that a group of people who suffer from depression
             | have lower serotonin levels when compared to someone who is
             | considered... not depressed. And we know that SSRI's
             | prohibit or prevent the bodies ability absorb serotonin
             | allowing it to accumulate and be more effective and pull it
             | in line with someone who is not depressed, resulting in the
             | depressed person becoming less or not depressed.
             | 
             | So. I'm unsure how my statement is untrue in response to
             | the parent statement stating we have no idea how they work.
        
               | mjfl wrote:
               | > We know that a group of people who suffer from
               | depression have lower serotonin levels when compared to
               | someone who is considered... not depressed.
               | 
               | I thought the whole point of the article was that there
               | is no solid evidence of a relationship between serotonin
               | levels and depression?
        
               | philliphaydon wrote:
               | The article seems to say that lower levels of serotonin
               | is not the /cause/ of the depression. But it doesn't
               | change the fact that most studies seem to conclude that
               | one of the things we can determine in people who suffer
               | from depression is that they have lower levels of
               | serotonin, and in some of those cases SSRIs help.
               | 
               | Not all forms of depression are caused by serotonin, and
               | anti-depressants may not always be the solution.
               | 
               | Again, my point is we know how SSRIs work and what they
               | do. What we do not know is why some people have lower
               | levels of serotonin or why they absorb it too quickly
               | compared to... non depressed people.
               | 
               | The issue with depression is that its a huge complicated
               | thing that we know a lot about, but at the same time, we
               | also know very little.
               | 
               | I would agree that we over perscribe medication for
               | depression as we do for MANY different things. In Asia,
               | antibiotics is handed out like candy when people are
               | sick. You have the common cold, boom you get antibiotics,
               | despite the fact that colds are caused by virus, and
               | antibiotics only helps with bacterial infections not
               | viral invections.
               | 
               | The US has a major problem with big phama where people
               | can be perscribed medicine for many things, and then have
               | side-affects resulting in more things being perscribed.
               | Painkills for injury > painkillers causing depression >
               | Prozac, Prozac causes insomnia > sleeping pills, sleeping
               | pills causes you to lose sexual drive > viagra, viagra
               | causes you to gain weight > apatite suppresents. It goes
               | on and on.
        
               | tomsto wrote:
               | This.
               | 
               | I wonder if a big part of the problem is that depression
               | and other mental illnesses are slightly unusual in that
               | they are categorised based on symptoms rather than
               | underlying biology, which are poorly understood. As a
               | diagnosis it's about as useful as 'chest pains'
               | 
               | Maybe (I am not a clinical psychiatrist) there are 1, 10,
               | or 100 very different underlying causes which would
               | indicate different treatment if only they were better
               | understood. But nonetheless the existing classification /
               | ontology is established and will be hard to displace.
        
       | narrator wrote:
       | The crisis in mental health is that suicide levels have been
       | rising since 2000. This is good evidence that the new drugs are
       | worse than the old drugs. If you look at consumers rating of
       | drugs they're on, mao inhibitor anti-depressants like nardil have
       | very high ratings, especially compared to SSRIs. Unfortunately,
       | the drug companies don't like competing with generics, so it goes
       | that the newest drug is considered the best drug.
        
         | actually_a_dog wrote:
         | > This is good evidence that the new drugs are worse than the
         | old drugs.
         | 
         | That's incorrect. There's good evidence that economics, in
         | combination with lack of funding for suicide prevention
         | programs is driving the increase in suicide rates. See
         | https://www.bbc.com/news/world-us-canada-44416727
        
         | robocat wrote:
         | > The crisis in mental health is that suicide levels have been
         | rising since 2000. This is good evidence that the new drugs are
         | worse than the old drugs.
         | 
         | Or this is good evidence that cellphone usage is causing
         | suicide (~1/3 of people in US had cellphones in 2000, ~100% do
         | now).
         | 
         | Your causality is poorly explained.
        
       | [deleted]
        
       | thelittleone wrote:
       | I highly recommend the book "plant medicines and the imaginal
       | realm".
       | 
       | I've worked extensively with indigenous curanderos (healers) many
       | of who view depression as a sickness undigested emotions and past
       | trauma. This sickness negatively affects perception of their
       | present moment.
       | 
       | In plant medicine ceremony, when past trauma is processed it's
       | frequently accompanied with throwing up which is called "purging"
       | or "getting well".
       | 
       | Outside of ceremony plants are often prescribed as a purgative
       | which are often drunk accompanied by copious water. Purging may
       | happen in both directions.
       | 
       | There is so much to experience in that field, so many lines of
       | beautiful inquiry and in ceremony often a feeling of eternal
       | present moment.
       | 
       | The book puts forward how depression and other sickness come from
       | an altered perception that can be restored by plant medicines.
        
       | refurb wrote:
       | This is completely unsurprising and indicative of how limited our
       | understanding of the brain is.
       | 
       | It reminds me of Pfizer's work on gabapentin. A professor from
       | Northwestern was working on GABA antagonists (by modifying GABA
       | itself) and eventually came up with the drug. It was hailed as a
       | great example of "structure-based drug design".
       | 
       | The drug was approved by the FDA and efficacious for a number of
       | issues like neuropathic pain. The submission documents from
       | Pfizer had all this data on the binding efficiency of the drug to
       | GABA receptors.
       | 
       |  _Except it didn 't work through the GABA receptor at all_.
       | 
       | After approval, more research was done and they said it worked
       | through glutamate channels. Then more work was done and it seems
       | most of its effect is through calcium channels.
        
         | DontchaKnowit wrote:
         | Do you have links to more info on this? Sort of an armchair
         | pharmocologist and had never heard this about gabapentin. I
         | thought it was a straight up gaba agonist like phenibut. But
         | makes sense that it would be different given its very unusual
         | dose response curve/self potentiation.
         | 
         | (Probably making anyone who actually knows what they're talking
         | about cringe. Take it easy, lol)
        
           | refurb wrote:
           | Gabapentin was designed as an antagonist (the structure is
           | basically GABA with a big bulky group on it).
           | 
           | You can just google older papers on gabapentin. Just like
           | most drugs it impacts a number of different receptors in the
           | body. We still don't fully understand them all.
        
         | clsec wrote:
         | Don't get me started on Gabapentin! I just got off of it after
         | 11 yrs (serious spinal cord injury - neuropathy). Initially,
         | after my surgery, I was on 12 different drugs (not all related
         | to my injury). Over the last 5 years I've been slowly weening
         | myself off of them one by one trying to figure out what was
         | causing me so many side effects. It turns out that the last
         | thing I quit was Gabapentin, which was last month. Amazingly,
         | all the side effects disappeared once I stopped. I'll never
         | take it again.
        
       | mathgladiator wrote:
       | As a member of the anti-psychiatry side after seeing primary care
       | doctors wreck my mother... I think we will see a sea change in
       | how we approach this with things like psychedelics.
       | 
       | I recently got treated with six weeks of Ketamine, and it works.
       | If you ever thought about rebooting your brain, then I recommend
       | it. However, you really have to surrender yourself to the
       | experience; it is a very intentional act.
        
         | PragmaticPulp wrote:
         | Ketamine treatment is interesting, but it's not really a
         | replacement for SSRIs. The anti-depressant effects of Ketamine
         | are unfortunately relatively short-lived. Tolerance also seems
         | to develop to the effects over time. There are some adventurous
         | providers experimenting with frequent ketamine dosing over long
         | periods of time, but the results haven't really been great from
         | what I've seen.
         | 
         | Also, a psychedelic experience is definitely _not_ necessary
         | for ketamine 's antidepressant effects. In fact, the more
         | responsible providers and studies are careful to keep peak
         | plasma levels low enough to avoid this, and it works just fine.
         | A lot of unscrupulous providers are using excessively high
         | doses to induce psychedelic experiences, but this isn't
         | actually supported by the evidence.
         | 
         | SSRIs and other traditional antidepressants will continue to be
         | mainstays of long-term depression treatment if for no reason
         | other than their sustainability and long-term efficacy is so
         | much better than ketamine.
        
           | armatav wrote:
           | So unbelievably unread and wrong.
           | 
           | Ketamines anti-depressant effects are some of the longest
           | lasting in pharmaceutical history.
           | 
           | Tolerance is carefully managed by your infusion provider to
           | not build up.
           | 
           | The long term efficacy is insanely good - which is why we
           | approved it in the first place.
           | 
           | The psychedelic experience is necessary to approach the more
           | permanent end of the spectrum - this is by the "evidence"
           | that you are not reading.
           | 
           | SSRIs continue to be a mainstay because they aren't $800 per
           | session with insurance and have an extreme margin. They are
           | far, far, far lower efficacy.
           | 
           | What are you doing my man? You just straight lied in almost
           | every sentence.
        
             | dang wrote:
             | Please don't break the site guidelines like this,
             | regardless of how wrong someone else is or you feel they
             | are. It makes the thread significantly worse.
             | 
             | Also, posting this way discredits your position, which in
             | the case that you happen to be right, is quite a bad thing.
             | 
             | If you wouldn't mind reviewing
             | https://news.ycombinator.com/newsguidelines.html and taking
             | the intended spirit of the site more to heart, we'd be
             | grateful.
        
           | jb1991 wrote:
           | How about psilocybin? One recent article posted here
           | suggested something like one dose every six months had
           | measurable impact on depression.
        
             | asdff wrote:
             | I support psychadelic legalization but at the same time I
             | wonder how much of the antidepressive effect of
             | psychadelics is just from giving space for thought in your
             | day to day life. For exmaple, the modern human wakes up,
             | starts scrolling instagram, goes to work, goes home,
             | continues scrolling instagram, then sleeps. There is no
             | period of reflection or introspective thought, since every
             | mundane activity where you could be reflecting internally,
             | e.g. washing the dishes or walking to the train, is
             | consumed by a podcast you have playing from your airpods.
             | For some people, taking a psychadelic drug is the only time
             | they give themselves to do nothing but think internally for
             | a few hours. I wonder if they would get the same benefit
             | just setting aside regular designated meditation time where
             | their thoughts aren't being interloped by all these forces
             | in modern society that vie for our attention.
        
               | mathgladiator wrote:
               | For my first infusion, I didn't wear an eye-mask and I
               | was kind of incapacitated as I watched people come and
               | check on my vitals. I felt this deep sense of caring that
               | we are all in this world together and love is the most
               | important thing.
               | 
               | It's not just time to reflect, but also a new perspective
               | which is hard to allow to enter the mind due to all the
               | anxieties of the world.
        
               | jb1991 wrote:
               | I agree with your general point, but psilocybin does a
               | heck of a lot more than give you space to think. It
               | temporarily (or, as studies suggest, perhaps more long-
               | term) also changes quite a bit about _how_ you think.
        
           | mathgladiator wrote:
           | I'm finding the biggest impact from the psychedelic
           | experience as a spiritual awakening, and the biggest thing I
           | feel is that I'm no longer in the nihilism trap.
        
             | _moof wrote:
             | I hope it sticks for you. For me it wore off completely
             | after only three weeks.
        
             | padolsey wrote:
             | Can you articulate how your brain allowed you to escape
             | from that trap? Did K affect you on some low-level
             | inarticulable level? Sincerely curious. Nihilism is a
             | struggle for me!
        
               | mathgladiator wrote:
               | So, what I can surmise is that I felt a deep connection
               | to the universe. You _feel_ the ramifications of not only
               | being a part of the universe, but also the part of the
               | universe trying to understand it.
               | 
               | I'd say I was an atheist before, but now I feel there is
               | something and that something is curious. It's like
               | consciousness is independent of the universe, and didn't
               | create the universe. Instead, it's trying to figure out
               | the puzzle. So, this tiny spark of faith cures nihilism
               | because I'm part of the consciousness, and as long I as
               | wake up and solve by piece of the puzzle, there is
               | meaning in that.
        
               | randomopining wrote:
               | 100% same feelings. But really it was never as much like
               | this with K as it was much moreso with the shrooms.
               | 
               | I can totally see why K is an immediate relief for people
               | who are immensely depressed. Within 1 hour it basically
               | rips you away from your sense of self, that you were so
               | unnecessarily attached to and that had all the depressive
               | emotions with it.
               | 
               | Shrooms seem like they produce a guttal connective
               | feeling to your surroundings and the natural world around
               | you. Longer lasting imo.
        
               | padolsey wrote:
               | That's beautiful. Thank you.
        
         | walrus01 wrote:
         | By far one of the weirdest things I saw recently was ketamine
         | clinic advertising on various forms of social media. Very
         | slickly produced.
        
       | 0xMatt wrote:
       | Low testosterone and too little exercise, just my opinion.
        
       | Linda703 wrote:
        
       | [deleted]
        
       | edkennedy wrote:
       | Much more comprehensive article on the study that is not behind
       | paywall here: https://www.nature.com/articles/s41380-022-01661-0
       | 
       | (Also it skips the editorialized title and presents the data)
        
       | SubiculumCode wrote:
       | It is depressing reading the comments here from people who know
       | nothing of this field, yet feel like they are qualified to spout
       | tons of unsubstantiated nonsense on a forum where we are
       | encouraged to only engage in the conversation when we actually
       | know something.
        
         | bowsamic wrote:
         | I'm not sure what you can expect since this problem affects so
         | many of us in such a huge way and yet no one has answers or
         | even stable advice
        
       | smm11 wrote:
       | I believe Vitamin D, sunshine itself, and not endlessly 'sitting
       | around' can do wonders, too.
        
         | missedthecue wrote:
         | I wonder if the number of people regularly smoking pot and the
         | number of people describing themselves as depressed have
         | anything to do with each other. Both are lines straight up and
         | to the right over the past 40 years.
        
       | throwawayacc2 wrote:
       | I have a theory which I can't substantiate, just anecdotes and
       | conversations I had throughout the years. But, I'm convinced a
       | lot of depression/anxiety stems from thinking too much and that
       | in turn is caused by an ever complex word with looser and looser
       | guidelines or norms.
       | 
       | I'm not making judgements weather this is necessarily good or bad
       | but rather observing.
       | 
       | In the past, even as recent as the 50s but certainly before the
       | 20th century, a persons course in life was mostly determined at
       | birth.
       | 
       | You're born, you play, you grow up, work the fields or a job, get
       | married, have kids of your own and die. Society was more rigid
       | and pretty much funnelled you through a "tried and tested path",
       | for good or for worse. And the lack of information made things
       | "simpler" in a way in the sense you had a small number of people
       | to get input from. Take child rearing for example. Many modern
       | people worry so much and research ways to "optimise" their
       | children for example ( I'm thinking of a lot of questions I saw
       | on the parenting stack overflow ) whereas in the last, you'd just
       | ask your own parents. And, since they were older, the assumption
       | was they knew what they where talking about, even if it was not
       | necessarily true. Same with health, same with sexuality,
       | relationships, a lot of things.
       | 
       | Essentially lack of information and a rigid social structure
       | meant fewer choices which meant less thinking. And less thinking
       | meant less depression and anxiety.
       | 
       | Now when you have a world of information at your hands, you have
       | way more things to think about, to worry about and to look for
       | information on how to fix or improve.
       | 
       | I'm not sure medication, even "working" one is a sustainable
       | solution to what appears to me to be an environmental problem
       | rather than a biological one.
        
         | retrac wrote:
         | > by an ever complex word with looser and looser guidelines or
         | norms
         | 
         | That reminds me of one of those weird little findings. People
         | with depression appear to more accurately estimate their
         | control (or lack of control) over a situation, than people who
         | are not depressed. Perhaps non-depressed people are just
         | delusionally optimistic about the chances of things going
         | wrong. (If true "overthinking" is probably related in some way
         | to this.)
         | 
         | > When participants were asked to press a button and rate the
         | control they perceived they had over whether or not a light
         | turned on, depressed individuals made more accurate ratings of
         | control than non-depressed individuals.[5] Among participants
         | asked to complete a task and rate their performance without any
         | feedback, depressed individuals made more accurate self-ratings
         | than non-depressed individuals.[6][7][8][9] For participants
         | asked to complete a series of tasks, given feedback on their
         | performance after each task, and who self-rated their overall
         | performance after completing all the tasks, depressed
         | individuals were again more likely to give an accurate self-
         | rating than non-depressed individuals.[10][11][12][13][14][15]
         | 
         | https://en.wikipedia.org/wiki/Depressive_realism
        
         | 999900000999 wrote:
         | Lost Connections is a great book on this.
         | 
         | Most people used to be apart of some form of community. You
         | made friends, made dinner together, found love , etc. In this
         | community.
         | 
         | Now their's none of that. Everyone is a disposable
         | interchangeable part. Instead of getting a stable job, and
         | having a foundation, now we're all gig workers. Or short-term
         | contractors. Back in the day, you'd work the same job most of
         | your life, and that's one of the ways you made friends.
         | 
         | Back when I lived in LA, I was lucky enough to be a part of a
         | fantastic apartment community. We cooked, and watched sports
         | together. While I had to leave for other reasons, I definitely
         | miss these guys.
         | 
         | The internet's a poor substitute, even at a bar my behavior is
         | restricted by social norms. In real life I've never had anyone
         | call me a slur, or personally attack me.
         | 
         | Online it's absolutely relentless, I don't use social media or
         | online dating for this reason.
        
         | martopix wrote:
         | I actually read a book that made a similar claim, although I
         | can't remember the title right now. It essentially said that
         | depression as we know it is an illness for the contemporary
         | world for the reasons you list. However, it made the point that
         | there were "different" mental health problems in the past,
         | which had to do more with the conflict against the more rigid
         | social structure -- same but opposite to how today we suffer
         | from the lack of direction that you describe well.
        
         | theptip wrote:
         | It's really complex. For a partial survey of that complexity,
         | see this SSC: https://slatestarcodex.com/2017/06/13/what-is-
         | depression-any....
         | 
         | Part of the problem in describing/treating this condition is
         | that depression is a huge constellation of overlapping causal
         | mechanisms. You may be describing one set of mechanisms but
         | it's certainly not the only one.
        
         | multiplegeorges wrote:
         | > And less thinking meant less depression and anxiety.
         | 
         | That's a pretty big claim. I know you're just putting out your
         | own personal theory and you're not trying to declare you have
         | the "answer", but I don't see how that follows.
         | 
         | A first step is establishing that depression is more prevalent
         | now than in the 50s. You'd have to account for the lack of
         | diagnosis then and find some other indicator of the true rate
         | of depression.
         | 
         | Not an easy task, for sure, but my first thought is that
         | depression just went untreated then and people became resigned
         | to their lot in life and suffered.
        
           | [deleted]
        
         | Zigurd wrote:
         | This is called nostalgia.
         | 
         | History was not neater, nor more uniform. The typical departure
         | point in 1950s conformism, with the assumption that prior
         | history must have been even more conformist.
         | 
         | But that's not how most of history treated gender roles,
         | marriage, work, etc.
        
         | sinecure wrote:
         | This is essentially what Ted Kaczynski (the Unabomber)
         | theorized and wrote about in his manifesto, that
         | industrialization and its abundance of comforts and options
         | have destroyed human happiness and that we would all be better
         | off if we lived simple hunter gatherer lives and knew nothing
         | of modernity or technology. That the hunter who catches a deer
         | and feeds his tribe is immensely more happy and fulfilled than
         | the stock broker who navigates high finance and city life, but
         | can't seem to get that promotion or afford that vacation house
         | his boss has.
         | 
         | Essentially the awareness of everyone else's lifestyle and
         | prosperity, amplified by the advent of print newspaper and now
         | social media, is the key destroyer of joy.
         | 
         | The peasant works his farm and feeds his family and raises his
         | kids. He knows he will not become king. He barely knows what
         | the king's lifestyle is. In modern America we are blasted with
         | thousands of kingly lifestyles 24/7 and are constantly asked,
         | why aren't we living like that? Why do I have to work? Why
         | can't I date the supermodel? Why do I have to struggle with
         | rent?
         | 
         | Our minds have not evolved to deal with this super-stimulus nor
         | the self comparison of endless idealized lifestyles we cannot
         | all realistically achieve.
        
         | themedes wrote:
         | Interesting concept, I must admit it seems a plausible
         | explanation. I also notice that Anxiety sufferers often
         | overthink things (its much more complex I know).
         | 
         | I guess information size is still exploding in volume and
         | depth, but perhaps in quite a few hundred years this will slow
         | and we catch up through several generations. Maybe then
         | depression or anxiety will be filtered out of subsequent
         | generations as we cope better?
         | 
         | Personally I suspected a lot of it was down to poor
         | nutrition/diet, exercise, night shift work, overall sleeping
         | less and exposure to screens/information. The main factor I
         | think is food e.g. sweeteners, sugars, e-number chemicals,
         | preservatives, and salt all altering our body chemistry.
        
         | rustybelt wrote:
         | Similarly, I don't think we're equipped for the level of
         | exposure to life-altering tragedy that mass/social media makes
         | available. I swear my wife subscribes to a dedicated "small
         | child dies in horrible freak accident" facebook feed. She is
         | constantly sharing these types of stories with me from around
         | the world. Logically, I know that these are actually extremely
         | rare events, but the constant exposure still makes us both more
         | anxious about the safety of our own children.
        
           | Taylor_OD wrote:
           | Good lord. I try to tell folks all the time that to some
           | extend you have to ignore news. Big world events are going to
           | find their way to you. Russian invading Ukraine is going to
           | end up being something you hear about regardless if you
           | follow the news at all.
           | 
           | The tragic stories of children getting bombed in Ukraine? The
           | photos? The gory details? That likely is only waiting for you
           | if you go searching for it.
           | 
           | I'm not advocating being ignorant. I'm advocating limited the
           | amount if tragedy you seek out on a daily basis. It isnt good
           | for ones head. It certainly doesnt make anyones life better.
        
             | hammyhavoc wrote:
             | I dunno about that. I know several doom-and-gloom mongers
             | who seem to get off on sharing the woes of the world in
             | group conversations. As a result, I've barely used Facebook
             | or any kind of social media since the pandemic began. Quite
             | literally, haven't used it this year except to post an
             | interview.
        
               | wizofaus wrote:
               | Discuss: HN qualifies as "social media". Why or why not?
        
         | froglets wrote:
         | My theory is that depression is situational and doing things
         | changes our situation, hopefully to one that is less
         | depressing. Thinking about things isn't very helpful if you
         | don't actually do anything. Medications can help people think
         | less and do more, and do seem to be one of many correlates of
         | depression.
        
         | grumple wrote:
         | > I have a theory which I can't substantiate, just anecdotes
         | and conversations I had throughout the years. But, I'm
         | convinced a lot of depression/anxiety stems from thinking too
         | much and that in turn is caused by an ever complex word with
         | looser and looser guidelines or norms.
         | 
         | This is not a new theory. It's called negative self talk, and
         | fixing that is one of the core approaches in treatment of
         | anxiety and depression.
        
         | hn8305823 wrote:
         | The good news is you don't seem to suffer from serious
         | depression.
         | 
         | If you did then you would know it is a very real _physical_
         | problem that positive thinking can 't really overcome. Not just
         | physically in terms of brain chemistry but you often literally
         | sink into your chair as if you were physically exhausted and
         | don't want to move.
         | 
         | Depression enforces negative thought templates. No matter how
         | good your life is going you will usually see the negative side
         | of things and be depressed mentally _and_ physically.
         | 
         | In a healthy person this is not the case. Your mood will vary
         | widely by the situation you are in but most of the time
         | positive thought templates will prevail and allow you to see
         | the best even in difficult situations. It also gives you the
         | mental/psycological energy needed to tackle difficult
         | challenges/problems. In a fully depressed state you have no
         | such energy no matter what your willpower is.
         | 
         | A healthy person has the mental and physical energy to tackle
         | the day even when it involves hard/tedious or unpleasant work.
         | 
         | One paradoxical thing about depression is that it can sometimes
         | actually feel _good_ , in a comforting "oh it's that familiar
         | feeling again" way. Usually that is just when you feel the
         | onset of symptoms before the bad feelings/thoughts/feelings.
        
         | s1artibartfast wrote:
         | I would generalize that even further to an abundance of
         | possibility. In terms of anxiety, possibility, however remote,
         | contributes to decision paralysis and over analysis.
         | 
         | In terms of depression, an abundance of possibility leads to
         | disappointment, deferred action, and deferred acceptance.
         | 
         | I can only speak for myself, but a preoccupation with trying to
         | optimize my life in the face of infinite possibility has led to
         | a tremendous amount of anxiety and at times depression. For
         | lack of a better term, it is an Omnivore's Dilemma of the Soul.
        
         | DigiDigiorno wrote:
         | ". . . I'm convinced a lot of depression/anxiety stems from
         | thinking too much . . ."
         | 
         | Sertraline (Zoloft) is used to treat both depression and/or
         | OCD. The dosages overlap too (OCD usually is a higher dosage I
         | believe). It is also used to treat anxiety.
         | 
         | I suspect there is a causal chain that goes like: compulsively
         | thinking > anxiety > depression/suicide. I'm not sure how
         | preventing reuptake of serotonin prevents compulsive thinking,
         | but I suspect the mechanism is closer to preventing the
         | thinking aspect and the other feelings are further down the
         | causal chain.
         | 
         | I am not an expert and I have only read a couple papers due to
         | someone in my life taking Sertraline and having it reduce their
         | OCD. (I thought it was only for depression based on my lay
         | opinion)
         | 
         | If anyone has read anything interesting about the thinking
         | aspect, please share links!
        
         | Sohcahtoa82 wrote:
         | I wonder how many people think they have depression, but are
         | actually simply suffering from despair.
         | 
         | Medication won't help you if you're living paycheck-to-
         | paycheck, dealing with landlords constantly increasing rents
         | while wages are stagnant, worried that getting sick and missing
         | a couple days of work will result in losing your place to live.
        
       | operator-name wrote:
       | I do not have full access to the comments published on the BMJ,
       | but the study is openly available at
       | https://www.nature.com/articles/s41380-022-01661-0
        
       | GauntletWizard wrote:
       | Depression is caused by a shitty life. Most people with
       | depression are trapped in an abusive relationship, though often
       | it is with themselves. They're trapped by fear of admitting
       | failure and making changes.
        
         | etchalon wrote:
         | This is deeply untrue.
        
         | imadierich wrote:
         | a lot of times its a abusive mindstate.... a lot of really
         | really down bad people have went on to do great things. its all
         | about your perspective
        
           | GauntletWizard wrote:
           | Absolutely. The best parts of modern psychology are CBT and
           | finding a better mind state. The drugs sometimes help shake
           | up your mind enough to find that.
        
       | nth_order wrote:
       | Yeah, but thats hardly news, we have known that for decades.
       | Otherwise direct serotonin releasers would be the most useful
       | ADs. But these mostly give people nausea and serotonin syndrome.
       | ADs work mostly by being FIASMAs, reducing inflammation and
       | oxidative stress, increasing neurogenesis and neuroplasticity,
       | increasing the activity of other monoaminergic systems, and the
       | serotonergic portion is mostly explained by downregulation of
       | 5-HT1A autoreceptors due to chronicly high extrasynaptic 5-HT
       | levels. This also explains the delayed action of ADs.
       | 
       | At least this is my knowledge from when I last researched this
       | topic in depth.
       | 
       | But that would be a little bit too much for the general public,
       | so it is simplified, to this annoying effect that everyone talks
       | of "low serotonin levels" where in fact the underlying systems
       | are way more complex.
        
         | harborseal wrote:
         | Yes, but people are still being told by their psychiatrists
         | that depression is caused by low serotonin levels as if it were
         | an objective fact. Seeing this happen made me lose a lot of
         | trust in the medical profession. Is it like this for all
         | illnesses or just mental ones?
        
           | hirvi74 wrote:
           | I was told by a psychiatrist that I respect that one day in
           | the future we may look back on psychiatry of today like we
           | look at blood-letting and lobotomies of the past.
        
         | Workaccount2 wrote:
         | Anytime I learn about bodily functions I become more and more
         | aware of how shit it's engineering is. Works amazing, sure, but
         | try and fix or debug anything? Good luck.
        
           | onefuncman wrote:
           | almost like life is an MVP that could pivot at any time
        
           | hutzlibu wrote:
           | Erm, are you aware of any other machine, that is able for
           | self repairing and self replicating in a complex and changing
           | environment?
           | 
           | I really would not call my body bad engineering, just because
           | I do not understand how it works in detail.
           | 
           | Rather the opposite, the more I learn, the more amazed I am,
           | how awesome it all is. The complex interactions of chemical,
           | electrical and physical components. (And who knows, maybe
           | even quantum field elements.)
           | 
           | I could not design anything remotely complex at all.
           | 
           | Also, I debug and fix my body all the time, or rather, my
           | body does this mostly in auto mode.
        
           | o_nate wrote:
           | I guess we should be grateful our brains are complex enough
           | to understand anything. Maybe it's too much to ask to ask
           | them to be able to understand themselves. They would need to
           | get more complex to understand themselves, but then that
           | complexity would make them more difficult to understand. It's
           | the snake trying to swallow its own tail.
        
           | _jal wrote:
           | Tractors don't know how to repair each other, either.
        
             | Dudeman112 wrote:
             | To be fair, tractors don't go on about how smart they are
        
           | rustybelt wrote:
           | Are you saying God likes to yeet buggy unmaintainable
           | spaghetti code directly into production?
        
             | rustybelt wrote:
             | Or maybe this reality is actually a dev environment.
        
             | N1H1L wrote:
             | DNA is spaghetti code exemplified. We are carried around
             | tons of dead viral DNA for example - what amounts to
             | shipping code with older code commented out.
        
               | rustybelt wrote:
               | I'm using this argument in my next code review meeting.
        
               | wizofaus wrote:
               | As a reviewer I'd then insist that your code was thrown
               | into a software-eats-software world and given a few
               | million reproductive cycles to see how it fares. If it's
               | still thriving you'll get your PR approval.
        
             | ryandvm wrote:
             | Hmm. We really ARE created in his image - at least I am.
        
         | ZeroGravitas wrote:
         | And now the opposite happens with headlines that imply "your
         | medication is suddenly revealed to be useless" when in fact
         | we've been aware that we don't know how it works for a while,
         | but we're still reasonably sure it helps, which perhaps
         | explains the increase in prescription more than the "serotonin
         | is the only thing that matters" theory which the experts ruled
         | out a while ago.
        
           | virtuallynathan wrote:
           | They barely work better than placebo, from what I saw in my
           | reading of the literature.
        
             | slibhb wrote:
             | Well, placebos work fairly well for depression. And it's
             | not like doctors can prescribe them...
        
               | User23 wrote:
               | They can however prescribe basically harmless pills that
               | do more or less nothing. Low dose vitamin pills are
               | sometimes used for this purpose.
               | 
               | Whether or not it's ethical for a doctor to tell a
               | depression patient that the depression is caused by a
               | treatable vitamin deficiency is another matter. Then
               | again, maybe it really is caused by a lack of
               | micronutients. After all we really don't understand
               | depression very well.
        
               | jack_pp wrote:
               | So the solution is prescribing something that has a lot
               | of unpleasant side-effects for a lot of people?
               | Medication that if you don't take will have SEVERE
               | withdrawal symptoms?
        
               | zasdffaa wrote:
               | I wonder why you say 'SEVERE' so severely. It doesn't
               | sound like you have any direct experience of this. I had
               | to come off them and it wasn't a problem. My biggest
               | fear, and it was huge, was that the depression would
               | return. It didn't.
        
               | MattRix wrote:
               | I had horrible withdrawal effects coming off
               | lexapro/escitalopram, it was literally the worst
               | experience of my life. I spent a month with maxed-out
               | anxiety, feeling like I was going to die any moment,
               | waking up at night with electric shocks running through
               | my body, etc. I wouldn't wish it on my worst enemy.
        
               | zasdffaa wrote:
               | OK, that's an SSRI which is what I had to come off
               | (prozac), with no major issues.
               | 
               | I'm not at all claiming it's a fun ride for everyone,
               | just giving my one data point that it's not inevitably
               | awful for absolutely everyone. Sorry you had to deal with
               | it!
        
               | hammyhavoc wrote:
               | Anecdotal. n+1.
        
               | zasdffaa wrote:
               | I'm not sure what you're saying?
        
               | guerrilla wrote:
               | Because it's pretty damned severe with SNRIs. You
               | probably only tried some SSRIs. Turns out not all
               | medications are identical.
        
               | zasdffaa wrote:
               | Yep, never taken SNRIs - for me it was straight prozac.
               | Side effects while on it weren't pretty though.
        
               | slibhb wrote:
               | SSRIs have mild side effects after the first few weeks.
               | Withdrawal varies but is generally manageable if you
               | taper slowly.
               | 
               | I'm open to alternatives but I'm convinced that
               | antidepressants help people.
        
               | wins32767 wrote:
               | I suddenly became allergic to SSRIs and had to go off of
               | them cold turkey. I didn't have any withdrawal problems
               | at all so it's not a universal issue.
        
               | niemal_dev wrote:
               | Wow, just wow. Quitting them cold turkey 0 problems,
               | incredible.
        
               | wins32767 wrote:
               | I'm not trying to minimize the problems other people have
               | had with withdrawal at all, just saying that it's
               | possible to have a variety of different outcomes being on
               | and off of them.
        
               | CharlesW wrote:
               | The AMA says they can if the patient is informed of and
               | agrees to their use. But wouldn't that significantly
               | impact their effectiveness?
        
             | NickM wrote:
             | There is also evidence that they might only work better
             | than a typical placebo because the side effects make them
             | an "active placebo", triggering a stronger placebo
             | response. i.e. if you take a pill that doesn't make you
             | feel any different, you may wonder if it's working, but if
             | you feel weird and have unpleasant side effects then you
             | know it's doing something.
             | 
             | This is particularly underappreciated in the research done
             | on these drugs, because a double-blind study isn't actually
             | double-blind if many of the participants can easily tell
             | whether they're in the placebo group due to very noticeable
             | side effects.
             | 
             | It's been mentioned in other comments, but I really
             | recommend the work of Irving Kirsch on this; he's a
             | brilliant scientist and his book The Emperor's New Drugs is
             | a real eye-opener.
        
             | swamp40 wrote:
             | They work fantastically, from what I have seen firsthand
             | many many times.
             | 
             | There is a _very good reason_ for it 's use in up to 20% of
             | the population in some groups in the US.
             | 
             | Just because we haven't pinpointed _why_ doesn 't matter a
             | bit.
        
               | dimal wrote:
               | "They work fantastically" is a statement that requires
               | many qualifiers.
               | 
               | They work fantastically for some subset of people. For
               | other people, they do nothing. For other people, they
               | have negative side effects that make them not worth
               | whatever benefits they provide. For some people, they
               | cause extreme negative effects when the medication is
               | removed. For some other people, they increase the chance
               | that they will commit suicide.
               | 
               | It does matter that we haven't pinpointed why they work
               | for some people, because if we did, we might be able to
               | avoid those negative effects and wasted time for the
               | people for which they don't work.
        
               | marcosdumay wrote:
               | If the effect is systematic, real, and measurable, it's
               | just a matter of giving the medication to the people that
               | benefit from it, and not giving it to the people that
               | don't.
               | 
               | The real question is by what level is the effect is
               | systematic, real, and measurable?
        
               | bowsamic wrote:
               | Who should I trust? Peer reviewed literature, or one
               | swampy boi?
        
             | bratsche wrote:
             | I've tried a number of antidepressant drugs and so far not
             | been able to notice much difference with any of them.
        
         | moth-fuzz wrote:
         | I have a friend that's convinced that her ADHD 'causes
         | depression' because her brain does not produce 'enough
         | dopamine'. I'm noticing more and more among my peers a
         | mythology around brain chemicals that's about as accurate as
         | the four humors but with a scientific-sounding veneer. All
         | brain function (and thus all bodily function, because the brain
         | _is_ the whole person  /s) can be traced back to the presence
         | or absence of a nominal amount of certain chemicals.
         | 
         | I wonder how the popular understanding of these processes will
         | evolve as more and more is discovered and understood.
        
           | oasisbob wrote:
           | The low-dopamine hypothesis for ADHD is a legitimate idea
           | still being actively studied.
        
             | hirvi74 wrote:
             | > legitimate idea still being actively studied.
             | 
             | Yes, but it is not conclusive.
             | 
             | I for one believe there are multiple types of ADHD. Be it
             | lifestyle induced, lead-exposure induced, TBI induced,
             | genetic, etc.. Us humans like to slap labels on things, but
             | life is rarely so cut and dry.
        
           | kemiller wrote:
           | I think ADHD causes depression because you get constant
           | negative feedback from (many) teachers & bosses.
        
             | root_axis wrote:
             | IMO, this hypothesis doesn't pass the smell test. One of
             | the defining qualities of clinical depression is that
             | personal success in life does not obviate the symptoms;
             | there are many widely know examples of beloved and
             | successful people being unable to overcome the burden of
             | crushing depression.
        
               | omniglottal wrote:
               | Being beloved and successful does not negate negative
               | feedback. In fact, rhetoric such as this is invalidating
               | the experience of those who must thereby insist that,
               | contrary to the signs you're seeing, they're actually
               | feeling down, else they must further internalize the
               | negative feedback which nevertheless exists in plethora.
               | The notion that anyone could claim precisely what
               | reasonably should bring another stranger happiness or
               | resolve their depression is pure hubris. The defining
               | qualities of this situation are all internal, and the
               | externalities used in your measurement are correllative
               | and either irrellevant or after-the-fact. A "smell test"
               | one might consider is of empathy: if your mind ran
               | quickly through various things which caught its
               | attention, yet couldn't follow through with focus until
               | resolution, negative feedback surely just recurs and
               | piles up - it is neither sufficiently affected nor undone
               | by positive feedback. OP's hypothesis smells true to me,
               | but I choose to sniff the roots rather than the flower
               | when we're looking for a cause more than an effect.
        
             | hirvi74 wrote:
             | It's true, and I alluded to this more in depth in a comment
             | in this chain.
             | 
             | Growing up in the semi-rural South East, USA, where kids
             | didn't get diagnosed with ADHD. (Fun fact -- I had 5 boys
             | who were my childhood friends that grew up with. We all
             | lived within 3 miles of each other, and all of us have ADHD
             | -- something in the water maybe?)
             | 
             | I didn't know I had ADHD until I was in a dark dark place
             | in my early 20s after 4 years of college (only took me 6
             | years lol).
             | 
             | I swear I have some kind of CPTSD from growing up with it.
             | I developed all kinds of healthy and unhealthy coping
             | mechanisms and a lot of anger and negative self-talk that I
             | struggle with still to this day.
             | 
             | I mean, I was chewed up and spit out by the public
             | education system, little league sports, other children's
             | parents, my peers, and even my own parents from time to
             | time. Constantly, day in and day out, being punished,
             | ridiculed, and humiliated for something I could not
             | control. I didn't want to be that way, and I still don't
             | want to be that way, but I am what I am.
             | 
             | I would not consider myself to be anything but average
             | intelligence, maybe even below average, but if it weren't
             | for sheer luck and a determination to prove everyone wrong,
             | then I do not think I would have survived.
        
               | bitexploder wrote:
               | There is a reason alcoholism (and drug addiction) and
               | ADHD strongly correlate. Coping and self medication are a
               | big deal when it feels there is no other tools available
               | or the negative externalities just get to be too severe.
               | Add in addictive personality traits common to ADHD folks
               | and it is quite a thing to overcome for more significant
               | ADHD sufferers.
        
           | wongarsu wrote:
           | I think a lot of this is about English (and probably most
           | languages) being vary lacking in ways to describe both short-
           | time and long-time mood effects. Talking about a dopamine
           | rush from completing a difficult task or an endorphin rush
           | from sport isn't very accurate, but despite everyone knowing
           | the feeling we never made better words for them.
           | 
           | Similarly "I've low dopamine" is just a modern version of "I
           | have the blues" or "I'm depressed". That's all good, as long
           | as everyone involved knows that it's a short hand, or maybe a
           | double-meaning of the word, not an actual medical
           | description. Just like somebody who is "a little OCD" has
           | none of the symptoms of actual OCD.
        
           | jugg1es wrote:
           | This is like the right/left brain generalization that
           | everyone seems to still believe in.
        
           | hirvi74 wrote:
           | > I have a friend that's convinced that her ADHD 'causes
           | depression' because her brain does not produce 'enough
           | dopamine'
           | 
           | Interesting, and she is somewhat right, but is wrong about
           | the 'enough dopamine' part, if I understand correctly. I have
           | heard that dopamine plays a role in ADHD (seems likely our
           | neurotransmitters don't absorb enough, but even that is an
           | overly simplistic explanation of the unknown and true
           | reality).
           | 
           | But yea, I also have ADHD and yes, it can cause depression.
           | Not due to dopamine, but because of the negative feedback-
           | loop ADHD can create.
           | 
           | For example, let's pretend I have some big assignment I need
           | to complete, and I am without access treatment (professional
           | or self-medication). If can't muster the "powers" to work
           | on/finish said assignment, I start to get extremely anxious
           | and/or I get depressed that I failed to finish said
           | assignment. Said anxiety/depression only makes my ADHD
           | symptoms worse which makes the anxiety/depression worse. Thus
           | I will struggle more to complete future work, which only
           | fuels said anxiety/depression even more, and the loop keeps
           | on iterating.
           | 
           | Though, sometimes the anxiety can be extremely helpful. I can
           | muster some insane kind of hyperfocus due to the pressure of
           | a looming deadline. I spent decades of my life relying on
           | anxiety to complete tasks, that even with treatment, it's
           | extremely hard to start and finish tasks without the anxiety.
           | 
           | It's an annoying and rough way to live, but oh well, I am
           | just grateful I do not have something worse.
        
             | TurkishPoptart wrote:
             | The Andrew Huberman podcast has a great episode on the
             | dynamics of ADHD. The brain does not properly distribute
             | dopamine to where it wants to send it, which challenges
             | your planning/reward matrices.
        
               | hirvi74 wrote:
               | As much as I love the Huberman podcast, I do feel he
               | spoke outside of his domain a bit too much on that
               | episode in certain sections.
               | 
               | Sure, he is far more credentialed than I am, but it's not
               | like he conducted any of the research himself. He is
               | merely spouting off what one could find on PubMed, APA,
               | etc..
               | 
               | While I think mindfulness can be beneficial, the research
               | he cited about just 17 minutes (or whatever arbitrary
               | number) can have permeant changes in the brains of
               | individuals both with and without ADHD to be ridiculous.
               | 
               | I also find any research relating to ADHD and fish oil
               | supplementation to be extremely dubious. It appears
               | research is starting to back-track on that one too.
               | 
               | That being said, I do really enjoy his podcast, but just
               | because he repeats something does not mean it's
               | true/untrue. I would have preferred him to have an
               | interview with an expert in the field of neuropsychiatry
               | or of equal qualification.
        
       | daniel-cussen wrote:
       | Suicidalism and depression come from having a bad life,
       | basically. All these quacks are trying to find what little
       | chemical they can pepper on or what little product they can
       | market. And society and especially psychiatrizing parents or
       | bosses keep looking for the one magic trick that fixes this
       | strange illness. Just make their life better! The actual
       | circumstances, stop oppressing them! Admit your subterfuge and
       | your child or employee will not suicide.
       | 
       | But admitting the subterfuge would sometimes amount to suicide.
        
         | king_magic wrote:
         | I have (and have always had) an awesome life. I've still
         | struggled with depression.
        
           | daniel-cussen wrote:
           | EDIT: Had and have always had an awesome life? The fuck?
           | Sounds counterfactual. Yeah a perfect life with no problems.
           | Wouldn't the depression make it not awesome?
           | 
           | But to narrow down, shrinks dream of some like sweetener or
           | artificial coloring they can add to all the shit the give
           | someone to make it taste good. A spoonful of sugar makes the
           | medicine go down! No it doesn't. It tastes bad because it's
           | poison. That is the point of taste. And the best medicine
           | tastes really good, Paltomiel, aspirin doesn't taste
           | particularly bad, there's another one but it doesn't taste
           | bad just really bitter, ah...alkaloids taste uh...well they
           | reconfigure your notion of sweet=good bitter=bad, then
           | there's dex, blood sugar, now sugar tastes like treacle. But
           | the whole thing of medicine tasting bad is just like
           | toothpaste tasting bad (sodium flouride), it tastes bad
           | because it is bad for you, you should avoid it, get a
           | toothpaste that doesn't have fluoride in it. Of course little
           | children have no way of stopping their parents from forcing
           | them to use this toothpaste, so they complain. And the
           | parents say no complaints, backed by violence. Coercion.
           | 
           | To the shrinks that said that to me, I say, you take all the
           | shit since it tastes so good, give me your pay for doing your
           | job for you, and yeah the seasoning...you'll need it.
        
       | MrYellowP wrote:
       | Depression isn't caused by chemical imbalances or whatever other
       | causes outside of ones responsibility. It's caused by ones life.
       | The people one shares his life with, the environment, ones
       | approach towards life itself. When you suffer from depression,
       | you suffer from your existence. Either because it is shit, or
       | because you make it shit and don't know better.
       | 
       | It's amazing how far we've come with ignoring that there are a
       | lot of things well within our control when it comes to mental
       | health, as long as we stop pretending they're not.
       | 
       | I'm not saying that everyone has the chance to change his life.
       | I'm saying that there's too much of a lack of self responsibility
       | in favour of dependence on "luck" and "external factors" which
       | "require" medication, because "there's nothing you can do."
       | 
       | I'm not blaming anyone but myself for my state and I certainly
       | don't try to pretend that it's outside of my control. It isn't. I
       | know that, because I can manage it all by myself, without
       | depending on anything. It doesn't change my life and I'm still
       | working on that, but if i blamed some random ass excuse of a
       | chemical imbalance for something that's actually my own fucking
       | fault, then I'll just stay like this forever.
        
       | chx wrote:
       | There's a significant population of science denying cranks and so
       | those who want to raise legit concerns about the quality and
       | alas, often motivation of medical studies are easily grouped with
       | those. But:
       | 
       | 1. There's no such thing as good / bad cholesterol. This is
       | complete baloney and Pfizer lost a staggering amount of money
       | when a drug raising good cholesterol got as far as human trials
       | -- and failed them. There is no significant evidence for
       | concluding that dietary saturated fat is associated with an
       | increased risk of coronary heart disease or cardiovascular
       | disease. There's growing amount evidence though that cholesterol
       | is a symptom and not a cause.
       | 
       | 2. The diagnosis and treatment of ADHD in adults but most
       | especially in children is extremely suspect. Last year there was
       | a study pretty much confirming it is overdiagnosed in children.
       | But even worse, whether ADHD is even a thing or multiple
       | conditions wrongly bundled under a single name is basically an
       | open question. We basically put labels on children with
       | "problematic behaviors" like "autistic spectrum disorder" and
       | "ADHD" and then eventually find that 30-80% of ASD children are
       | meeting criteria for ADHD. First of all what sort of study is
       | 30-80%? But if the higher end is true, the question strongly
       | arises: are these even two things?
       | 
       | 3. I would bet dollars to doughnuts in a few decades we will look
       | at all current nutrition advice to something akin of medieval
       | quackery. How is this not self evident: genes obviously affect
       | how foodstuff interact with our bodies thus any sweeping
       | generalization is inherently suspect or most likely complete
       | baloney. Like, how can anyone seriously think _only_ lactose
       | intolerance is an inherited genetic trait.
       | 
       | I would need to dig into my notes if someone needs them but a
       | group of statisticians at a university started to look into
       | medical studies and then FOIA the raw data and found like 80% of
       | them cherry picking the data.
       | 
       | The incentives are not exactly at the right place.
        
         | briefcomment wrote:
         | Add polyunsaturated fats to that list
         | 
         | If you really want to dive into the wealth of counter narrative
         | research that's being conducted, here's a huge collection
         | http://haidut.me
        
         | drc500free wrote:
         | > Last year there was a study pretty much confirming [ADHD] is
         | overdiagnosed in children.
         | 
         | That paper is very clear that they did not study misdiagnosis.
         | They are a bit jargony with the use of "overdiagnosed."
         | 
         | "Overdiagnosed" does not mean incorrectly diagnosed, it means
         | that there are subgroups who get a net harm from being treated.
         | 
         | A more understandable term for what they measure is
         | "overtreated." The solution is likely better protocols for mild
         | cases, not to state that ADHD is not a thing.
        
         | klodolph wrote:
         | > I would bet dollars to doughnuts in a few decades we will
         | look at all current nutrition advice to something akin of
         | medieval quackery.
         | 
         | All current nutrition advice? Does this equally include the
         | nutrition advice that your cousin gives on Facebook, as well as
         | the advice given by doctors of nutritional science?
         | 
         | I get where this skepticism comes from. Nutrition is
         | complicated, and there's a lot of bad advice shared by random
         | people you meet. There's also the diet supplement aisle at your
         | local grocery store, which is full of poorly-regulated products
         | with dubious claims. (At least, in the US, we have these. They
         | are not regulated as drugs.)
         | 
         | At the same time, nutrition-based interventions are some of the
         | most effective public health policies we've ever implemented.
         | In the US, we have programs like WIC. We have iodized salt. We
         | cure blindness in children. We cure scurvy. These are all
         | amazing things--things which we kind of take for granted,
         | because we're not ever exposed to scurvy, childhood blindness,
         | etc.
         | 
         | This is not the first time I've heard such extreme skepticism
         | of nutritional science and it just _boggles the mind_ because
         | if you talk to someone who works in the field, they have
         | amazing success stories to talk about.
        
         | refurb wrote:
         | _There 's no such thing as good / bad cholesterol._
         | 
         | This is untrue. There is lots of data to suggest elevated LDL
         | is a risk of cardiovascular disease and that high HDL lower
         | risk.
         | 
         | Pfizer's drug failed because of safety issues, not because
         | "There's no such thing as good / bad cholesterol".
        
           | chx wrote:
           | > there is lots of data to suggest elevated LDL is a risk of
           | cardiovascular disease
           | 
           | Elevated LDL is a symptom of inflammation. It is not a cause
           | and lowering it doesn't help. The research mixed up cause vs
           | correlation.
        
             | refurb wrote:
             | I love reading medical advice on HN.
             | 
             | Genetic errors which cause high LDL levels result in
             | significant cardiovascular disease. It's a very strong
             | cause and effect.
             | 
             | I won't argue that inflammation doesn't play some role (it
             | seems to play a role in many diseases), but I wouldn't
             | dismiss current medical opinion on LDL.
             | 
             | https://en.wikipedia.org/wiki/Familial_hypercholesterolemia
             | 
             |  _Familial hypercholesterolemia (FH) is a genetic disorder
             | characterized by high cholesterol levels, specifically very
             | high levels of low-density lipoprotein (LDL cholesterol),
             | in the blood and early cardiovascular disease._
        
               | imtringued wrote:
               | Why aren't you adjusting for LDL subfractions? Seriously,
               | yes having too much LDL can be a sign of having harmful
               | subfractions but that doesn't mean high LDL actually is
               | harmful or low LDL is healthy.
        
               | refurb wrote:
               | I'm not sure that changes my argument than "There's no
               | such thing as good / bad cholesterol." is a false
               | statement?
        
             | toomuchtodo wrote:
             | High sugar diet the cause ("Western Die" and whatnot)?
        
           | imtringued wrote:
           | > There is lots of data to suggest elevated LDL is a risk of
           | cardiovascular disease and that high HDL lower risk.
           | 
           | There is zero data to suggest that once you adjust for
           | oxidized/damaged LDL.
           | 
           | Smokers don't have elevated LDL but they still suffer the
           | effects of inflammation/oxidization that ultimately lead to
           | cardiovascular disease. If you want to guarantee
           | cardiovascular disease just eat straight up oxidized
           | cholesterol in the form of trans fats.
        
             | refurb wrote:
             | _" eat straight up oxidized cholesterol in the form of
             | trans fats"_
             | 
             | Trans fats aren't oxidized.
             | 
             | Like I said, I _love_ reading HN health comments.
        
         | emodendroket wrote:
         | > 2. The diagnosis and treatment of ADHD in adults but most
         | especially in children is extremely suspect. Last year there
         | was a study pretty much confirming it is overdiagnosed in
         | children. But even worse, whether ADHD is even a thing or
         | multiple conditions wrongly bundled under a single name is
         | basically an open question. We basically put labels on children
         | with "problematic behaviors" like "autistic spectrum disorder"
         | and "ADHD" and then eventually find that 30-80% of ASD children
         | are meeting criteria for ADHD. First of all what sort of study
         | is 30-80%? But if the higher end is true, the question strongly
         | arises: are these even two things?
         | 
         | You know, just the other day I read about some brain scan study
         | which suggested high-functioning autism looked, in brain scans,
         | more like ADHD than like profound autism. But I think to some
         | extent this sort of problem is inevitable if you're trying to
         | dream up a taxonomy for conditions entirely from how they
         | present themselves with a limited understanding of their
         | biological basis.
        
         | eyelidlessness wrote:
         | > The diagnosis and treatment of ADHD in adults but most
         | especially in children is extremely suspect.
         | 
         | Go on...
         | 
         | (I'm adult diagnosed, for disclosure, but please do go on and
         | tell me how suspect my diagnosis was, how I shouldn't have been
         | diagnosed as a child, how my medication is harmful. Go on and
         | tell me about my life which you know better than I do.)
        
           | photochemsyn wrote:
           | I think OP is just saying that 'ADHD' is not that valid of a
           | diagnosis, in terms of any kind of underlying 'pathology'.
           | The fact that many people appear to benefit from the use of
           | 'medication' (i.e. amphetamines and derivatives, from
           | Adderall to Desoxyn(methamphetamine) to Ritalin), is mostly
           | unrelated to any 'diagnosis'.
           | 
           | Personally I think all drugs should be legal and people
           | should be able to take whatever they think helps them,
           | although I always recommend the 'less is more' mentality and
           | would urge people not to develop dependencies.
        
             | eyelidlessness wrote:
             | > I think OP is just saying that 'ADHD' is not that valid
             | of a diagnosis
             | 
             | I understand this in the comment's expression too, and it's
             | emphatically wrong.
             | 
             | > benefit from the use of 'medication' (i.e. amphetamines
             | and derivatives, from Adderall to Desoxyn(methamphetamine)
             | to Ritalin), is mostly unrelated to any 'diagnosis'.
             | 
             | You're incorrect.
             | 
             | > Personally I think all drugs should be legal and people
             | should be able to take whatever they think helps them
             | 
             | I agree, but this has nothing to do with the validity of
             | actual diagnoses of actually treatable conditions.
        
               | Elof wrote:
               | I think the point is that actual diagonoses are often
               | wrong and potentially harmful, which I agree with. I
               | share a bit of your story, getting diagonised with ADHD
               | benefited me greatly and led me down a path that likely
               | saved my life. At the same time, while many people are
               | helped by the medical system many others aren't and psych
               | drugs are an area where there is a lot of finger waving
               | in how drugs are perscribed.
        
             | chx wrote:
             | You got it. The shakiness of this entire thing also shows
             | in how the medication for ADHD is chosen: by trial and
             | error. For real.
        
               | tptacek wrote:
               | That's how medication for all sorts of things is chosen.
        
               | kortex wrote:
               | Ignoring the fact that basically all drug development
               | outside of the computational stuff is large amounts of
               | trial and error, there is ample evidence that ADHD
               | results from dysfunction of specific neural pathways, and
               | stimulant medication benefits ADHD individuals (more than
               | just "speed helps everyone focus").
               | 
               | > This literature is increasingly contributing to the
               | notion that the pathophysiology of ADHD reflects abnormal
               | interplay among large-scale brain circuits. Moreover,
               | recent studies have begun to illuminate the mechanisms of
               | action of pharmacological treatments.
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876939/
        
           | whimsicalism wrote:
           | e: [deleted]
        
             | eyelidlessness wrote:
             | What's your point?
        
             | mf2hd wrote:
             | Focus.
        
             | phs318u wrote:
             | This is HN not Slashdot. Please don't turn it into
             | Slashdot.
        
           | pindab0ter wrote:
           | Just because you might have gotten a diagnosis that helped
           | you doesn't mean everyone has.
           | 
           | I for one am actually interested if he can back up that
           | claim. So when you as them to "Go on...", please leave it at
           | that. There's no reason to be snarky.
        
             | chx wrote:
             | doi:10.1001/jamanetworkopen.2021.5335
             | 
             | > Findings In this systematic scoping review of 334
             | published studies in children and adolescents, convincing
             | evidence was found that ADHD is overdiagnosed in children
             | and adolescents. For individuals with milder symptoms in
             | particular, the harms associated with an ADHD diagnosis may
             | often outweigh the benefits.
        
               | tptacek wrote:
               | https://news.ycombinator.com/item?id=32161542
        
               | harry8 wrote:
               | Hey can you do that and provide something similar about
               | cholesterol? I'd appreciate it. Thanks.
        
             | eyelidlessness wrote:
             | You have the benefit of being casually disconnected from
             | the topic and presenting yourself as intellectually
             | curious. I have the experience of being alive because I was
             | diagnosed and treated. Your curiosity about whether I get
             | to live or die is up to you, but my place to speak to that
             | isn't up to you until I'm dead.
        
               | handedness wrote:
        
               | eyelidlessness wrote:
               | What's your point?
        
               | detaro wrote:
               | That you are telling them about their life which you
               | apparently know a lot about.
        
           | tuxie_ wrote:
           | Don't take it personal. Both things can be true, you can have
           | adhd and adhd can be overdiagnosed, doesn't mean that none of
           | those diagnostics are valid.
           | 
           | I'm sure you must be tired of people telling you about how
           | overdiagnosed adhd is, I'm sorry about that, but don't take
           | it personal, it's just a person on the internet.
        
             | peyton wrote:
             | GP also claimed the treatment is extremely suspect yet
             | provided nothing to back up the claim. Does GP think the
             | treatment does not work? AFAIK it is among the most
             | treatable psychiatric illnesses.
        
               | chx wrote:
               | doi:10.1001/jamanetworkopen.2021.5335
               | 
               | > Findings
               | 
               | > In this systematic scoping review of 334 published
               | studies in children and adolescents, convincing evidence
               | was found that ADHD is overdiagnosed in children and
               | adolescents. For individuals with milder symptoms in
               | particular, the harms associated with an ADHD diagnosis
               | may often outweigh the benefits.
               | 
               | What I mean is that we feed children Ritalin without a
               | second thought. It's absolute nuts. There are many many
               | ways to work with ADHD which doesn't require giving a
               | children meds. We should be _way_ more cautious about
               | doing that.
        
               | tptacek wrote:
               | This study comes nowhere close to supporting the claim
               | you made upthread, that "The diagnosis and treatment of
               | ADHD in adults but most especially in children is
               | extremely suspect". The claims it makes are much narrower
               | than your claim (in particular, it focuses on mild ADHD
               | cases, and the "harms" it discusses from medication are
               | subjective, like the diagnosis providing "an excuse for
               | problems".
        
             | eyelidlessness wrote:
             | > Don't take it personal
             | 
             | Oh I take it personally. I'm alive today because I sought
             | diagnosis and treatment. I very nearly wasn't alive from
             | the consequences of being undiagnosed and untreated. I very
             | probably would be dead today if I had taken this "just
             | person on the internet" more seriously than I already had.
             | I'm more than tired of people offering their ignorant
             | opinions about stuff they don't understand.
        
               | willcipriano wrote:
               | On the other hand, the state threw a ADD diagnosis on me
               | because I was bored in school, pumped me full of a
               | methamphetamine analog and put me into classes with
               | profoundly disabled people ruining my social life from a
               | early age. I'd stare at the wall in my bedroom for hours
               | due to the drugs, eventually my parents stopped giving
               | them to me when I was at home, but that lead my dad to
               | try them, and eventually get addicted to meth proper
               | himself.
               | 
               | I dropped out at 15 and taught myself computer science,
               | so it was all provably horseshit but it sure made my life
               | harder as a child.
        
               | eyelidlessness wrote:
               | In all seriousness, I'm sorry you went through this. I
               | also grew up with a parent and family with addiction. I'm
               | in no place to assess anything about your life, but what
               | you describe is consistent with the diagnosis. And
               | unfortunately your dad taking your meds and becoming an
               | addict is consistent too.
               | 
               | ADHD is frequently hereditary, and substance abuse and
               | addiction are common for people with undiagnosed ADHD.
               | 
               | Your own story of dropping out and teaching yourself
               | isn't just familiar to me, it's similar to both my
               | brothers' stories as well.
               | 
               | I'm sorry you experienced this the way you did. I wish
               | you had better medical care, and better parental
               | guidance. I hope the life that you've made for yourself
               | is joyful and prosperous, and I hope if it's ever not
               | you'll find your way to that however it makes sense.
        
               | [deleted]
        
               | wpietri wrote:
               | As somebody who was diagnosed with ADHD in my youth and
               | who has tried various medications, I've reached the point
               | of suspecting that the disease model is just a poor fit
               | here.
               | 
               | Does my brain work differently than other people? Yes.
               | Would this have been a problem for me in any pre-
               | industrial society? (Which, to be clear, is most of human
               | history?) I don't think so. Is it a problem for me when I
               | have a fair bit of control over the work I do? Not
               | really! I only experience it as a problem when I am
               | expected to function in contexts with industrial-age
               | labor models, where there's a hierarchy that expects me
               | to labor like a robot in line with how my betters have
               | decided how the work should be done.
               | 
               | So I can entirely believe that authority figures over-use
               | ADHD as a diagnosis so that their lives are easy. Reading
               | through the DSM, it seems to me there are quite a number
               | of diagnoses that could be used as Authority
               | Inconvenience Syndrome. And I don't think I've ever seen
               | one where people might need treatment for being too
               | obedient.
        
               | [deleted]
        
               | imtringued wrote:
               | I find the idea that we are born defective to be
               | inherently suspect.
               | 
               | It is quite illogical but very popular because well
               | adapted people can just talk about superior genes and how
               | everyone else has inferior genes and they can never
               | change anything about that except with extensive medical
               | treatment.
        
               | wpietri wrote:
               | For sure. I've read some really interesting stuff under
               | the "medicalization of deviance" label. A classic example
               | being how homosexuality was treated as a psychological
               | illness because the dominant group saw it as a societal
               | offense.
        
               | emptysongglass wrote:
               | I want to support you, also toward HN, that I do take it
               | personally and am pretty exhausted by people all the way
               | back to both of my parents denying I have a condition.
               | 
               | People of the internet: there are better things you can
               | be doing than playing armchair psychiatrist, especially
               | by invoking notions that can ultimately be harmful to a
               | class of people who have forever been told they just need
               | to _put in more effort_. You don 't know what it's like
               | to live with this so please stop with the conjectures.
               | Thank you.
        
               | dang wrote:
               | We're glad you're alive. Please don't take HN threads
               | into flamewar.
               | 
               | People have different experiences/backgrounds. It's both
               | inevitable and natural that there are different points of
               | view on this or any other complex topic.
               | 
               | https://news.ycombinator.com/newsguidelines.html
        
               | biohacker85 wrote:
        
               | wpietri wrote:
               | I see people downvoting this and I think that's a
               | mistake. There's a fair bit of stigma for all sorts of
               | mental health treatment, and I think that's a reasonable
               | thing to be angry about. It's possible that some people
               | are over-treated and also that some people are under-
               | treated. People who have suffered from either end of that
               | are allowed to be angry about their suffering.
        
         | jb1991 wrote:
         | I would be curious to see discrepancies in ADHD diagnosis
         | between countries. You hear about it all the time in the U.S.
         | but rarely in many other places, including Europe.
        
         | TulliusCicero wrote:
         | > then eventually find that 30-80% of ASD children are meeting
         | criteria for ADHD. First of all what sort of study is 30-80%?
         | But if the higher end is true, the question strongly arises:
         | are these even two things?
         | 
         | 80% of ASD kids meeting criteria for ADHD doesn't mean that 80%
         | of ADHD kids meet the criteria for ASD. ADHD seems a lot more
         | common.
        
       | pddpro wrote:
       | Anecdote but I always noticed change in sleep patterns after
       | starting antidepressants. Actually, terminal insomnia (you wake
       | up and then are unable to fall asleep) are characteristic of
       | chronic depression. Add to this that SSRI causes increase in
       | sleep hours (maybe even quality?) and then you have a theory
       | about how it might just have been due to lack of sleep after all?
        
         | cpncrunch wrote:
         | Given the placebo effect is 75% of the effect of
         | antidepressants, and placebos have a large effect on sleep, I
         | would say that the placebo effect is the first thing that
         | should be considered.
        
       | dotcoma wrote:
       | I thought it was widely accepted by now that the serotonin thesis
       | was a bullshit story spread, among others, by Al Gore's wife,
       | maybe in good faith, maybe not.
       | 
       | Edit: Tipper Gore; I did not remember her name (I'm not from the
       | US).
       | 
       | I read she was a big fan of the serotonin theory in a book (whose
       | title I don't remember at the moment).
        
         | dotcoma wrote:
         | Edit #2: The book is: Lost Connections: Uncovering the Real
         | Causes of Depression, by Johann Hari
         | 
         | In chapter 2: The year after I swallowed my first
         | antidepressant, Tipper Gore -- the wife of Vice President Al
         | Gore -- explained to the newspaper USA Today why she had
         | recently become depressed.
         | 
         | Just so that it's clear: I have nothing against Al Gore --
         | except that he lost the election.
        
       | eyelidlessness wrote:
       | There's no convincing evidence that discussing medical aspects of
       | mental health is productive on HN. Currently my comment that I'm
       | _alive_ has been downvoted at least half a dozen times because I
       | had the temerity to still be alive, be glad to say so, be
       | grateful for my psychiatric care, and reject that any of that is
       | "suspect". This isn't the place to discuss psychiatry. Talk to
       | your doctor.
        
         | dang wrote:
         | Please don't post offtopic flamewar comments, regardless of how
         | wrong other people are or you feel they are. It just makes
         | everything worse. Also, please don't go on about downvotes.
         | That's in the site guidelines too:
         | https://news.ycombinator.com/newsguidelines.html
         | 
         | Edit: I assume you're talking about
         | https://news.ycombinator.com/item?id=32161183, which was
         | correctly downvoted for being a flamewar comment. Please don't
         | post comments like that or
         | https://news.ycombinator.com/item?id=32161488 or
         | https://news.ycombinator.com/item?id=32161557 to HN.
        
           | eyelidlessness wrote:
           | > Please don't post comments like that or
           | https://news.ycombinator.com/item?id=32161488
           | 
           | This is the one I was referring to. I'll admit that the first
           | one you linked was not productive, but I'm reasonably sure
           | you're taking a less charitable interpretation of this one in
           | light of that. As far as what makes "everything" worse, the
           | prevalence of attitudes like those I was challenging are the
           | reason I almost died without treatment. But if they're
           | politely stated, no harm no foul?
        
             | dang wrote:
             | > But if they're politely stated, no harm no foul?
             | 
             | That's not at all how we moderate HN. But IIRC (it's been a
             | few hours since I've read the thread) your comments put an
             | extreme personal skew on the comments you were taking
             | offense at and then breaking the rules in reply to.
             | 
             | It's natural and understandable that this happens sometimes
             | on topics where you feel strongly (I don't mean you
             | personally, but any of us). However, natural and
             | understandable does not equal ok. On the contrary: we all
             | need to catch ourselves when we're getting carried away
             | like that, and either edit our posts to be within the site
             | guidelines, or just walk away. I find it helpful, in such
             | cases, to remember that the internet is to a first
             | approximation wrong about everything, and there's nothing
             | that any of us can do about it.
        
           | adamwk wrote:
           | Why is this an off topic flame war comment but "I'm too tired
           | to write a paragraph but SSRIs kill" is fine? The moderation
           | here rewards engineer's disease where we first principling
           | our way to warning people to ignore Dr.'s suggestions as long
           | as everyone's smiling at each other.
           | 
           | It's like an anti-vax YouTube video where any dissenting
           | opinion is flagged until mods give up and remove it from the
           | front page. It's the same thing with abortion or anything
           | else that isn't a Rust article.
        
             | dang wrote:
             | Yes, that was also a bad comment. It wasn't aggressive to
             | other users, though, which is an important difference from
             | a moderation point of view.
             | 
             | HN is an internet watercooler. People come here to have
             | casual, curious conversations. That requires being allowed
             | to be wrong, to think out loud, to shoot the shit, to
             | exchange. Imposing some sort of correctness requirement,
             | besides being impossible (how on earth would we enforce
             | such a thing without a truth meter?), would kill
             | conversation and therefore kill the forum.
             | 
             | You guys are overgeneralizing based on seeing comments you
             | dislike. I understand (believe me I understand) how
             | frustrating that is, but there are just as many people who
             | agree with you, probably more. The fact that there's a
             | range of views here is normal, inevitable, and fine.
             | 
             | HN has always operated on the principle that readers are
             | smart enough to make up their own minds, i.e. to find their
             | way through internet bullshit however they choose to do so.
             | I don't see any reason to change that operating principle.
        
         | mlang79 wrote:
         | Complaining about being downvoted on a related topic are not
         | productive either.
        
         | _moof wrote:
         | Indeed. And I can't help but notice that every discussion is
         | rife with people singing the praises of psychedelics, but TMS
         | is never, ever mentioned. If people were genuinely interested
         | in alternatives to SSRIs for the sake of efficacy, you'd think
         | an FDA-approved, non-pharmaceutical, non-invasive treatment
         | would come up at least once.
        
           | Negitivefrags wrote:
           | TMS gives me the creeps. I mean ultimately you are inducing
           | current in the brain with magnetic fields.
           | 
           | It boils down to the same mechanism of action as electro-
           | shock therapy. Presumably with a lot less destruction of
           | neurons of course.
           | 
           | Now electro-shock is one of the most effective at treating
           | depression, and I guess that might be why TMS might be
           | effective too.
           | 
           | But I think the reason I ultimately wouldn't do it is just
           | that it feels like physically altering my brain and it's a
           | hard pill to swallow. Just like I would be hard pressed to
           | accept a treatment like someone surgically excising a chunk
           | of my brain matter even if a doctor told me it was 100%
           | effective as a cure.
           | 
           | Perhaps this is irrational but I just can't shake it.
        
         | pjc50 wrote:
         | HN is only really great on technical issues. Everything else
         | suffers from Engineer's Disease, where a person who has read
         | half a dozen articles suddenly imagines they know a complete
         | discipline. This thread is a prime example of "my googling
         | trumps your life experience".
         | 
         | That said, in countries where pharmaceutical manufacturers are
         | allowed to _market_ prescription medicines, and one was
         | recently convicted for pushing addictive substances on huge
         | numbers of people, a certain amount of skepticism may be
         | warranted.
         | 
         | ("medicine X saved my life" and "a large number of people who
         | don't get any real benefit for medicine X are being sold it"
         | and "medicine X may have extremely bad side effects for some
         | people" may co-exist, as well)
        
           | ChildOfChaos wrote:
           | I think this 'Engineer's disease' is just what society is
           | now. Everyone thinks they know about everything, because they
           | read something online/have access to google. Everyone is an
           | expert.
           | 
           | You have people arguing very strongly about things they know
           | nothing about and sometimes if you actually know anything
           | about it, it's painful to read just how bad some of the
           | things people are saying, being a logical person, I try to
           | point out what they are saying doesn't make sense, but it's
           | wasted because that person just doubles down on whatever it
           | is that they believe.
           | 
           | The most powerful lesson from noticing this effect and the
           | hardest thing to do, is not actually taking that step back
           | and just not getting involved, it's also in realising that
           | i'm likely doing that too, so it's better to try and step
           | back and approach such comments with a more curious and open
           | mind, rather than one of thinking i'm an expert.
        
         | benevol wrote:
         | It's not that anti-depressants shouldn't be an available
         | choice.
         | 
         | It's that natural remedies such as psilocybin and LSD which
         | have proven their worth for a very, very long time are still
         | being blocked by you-know-which industry.
        
           | grapeskin wrote:
           | As much as I think LSD helps, I don't think it's ever been
           | found naturally. It's synthesized.
        
         | bluecalm wrote:
         | Doctors aren't some magical people who know everything. They
         | read the same books and studies available to you. They have
         | their own biases, not much time for an individual patient. They
         | often stopped educating themselves once reality of long work
         | hours set in.
         | 
         | Just talk to you doctor might the worst popular advice on the
         | Internet. My experience is the opposite: until you take matters
         | in your own hands, experiment with various treatments and
         | preferably find an open minded doctor who is willing to help
         | you along the way (not only with advice but mainly with
         | providing access to medication) it will not work. It might work
         | if your problem is simple and typical but it won't otherwise.
         | 
         | The reason is obvious: you are likely as smart as your doctor.
         | They might have more experience and general knowledge but they
         | have an hour (if you're very lucky) for you and you have all
         | the time in the world to catch up and figure it out.
         | 
         | Yeah, talk to doctors if you're the kind of person who drifts
         | to homeopathy or other shamanism but please don't solely rely
         | on them when it comes to your health of you have a bit of a
         | brain.
        
         | epups wrote:
         | For every successful case as yours, there are many people
         | suffering due to side effects that might include suicide.
         | Therefore, your anecdotal evidence is of limited value, even
         | though - gladly! - your treatment worked for you.
        
         | Etheryte wrote:
         | Have you considered that your comment may have been downvoted
         | because you come across unnecessarily hostile, not because of
         | some absurd attack on your person? Similarly, any space is a
         | good space to discuss and spread awareness on mental health --
         | even if only one person finds an idea to help them, whatever
         | their situation may be, it's already a massive positive.
        
           | irjustin wrote:
           | > because you come across unnecessarily hostile
           | 
           | And possibly justified.
           | 
           | A lot of us are armchair psychiatrist from reading articles.
           | OP that you're replying to lives this type of medication and
           | attributes being alive right now to it while a lot of us who
           | have only read articles sit and debate.
           | 
           | A number of these comments can come across as "just eat
           | healthier" to an overweight person or "don't be sad".
        
             | im3w1l wrote:
             | About 15% of American adults are _currently_ on
             | antidepressants. I tried but failed to find how many people
             | ever used it. But it goes without saying that it should be
             | be even higher. In other words, antidepressant use is very
             | common and many people will be drawing on personal
             | experience. That might not feel comfortable divulging that
             | about themselves.
        
             | [deleted]
        
       | PragmaticPulp wrote:
       | SSRIs raise extra-synaptic serotonin levels within the first hour
       | of taking them. However, their efficacy against depression takes
       | weeks or even months to manifest. We've known this for decades,
       | and as a result the "chemical imbalance" theory of depression
       | hasn't been a real contender in depression research for a long,
       | long time.
       | 
       | The key thing to understand is that serotonin levels don't have
       | to be low for SSRIs to induce positive changes. SSRIs don't just
       | "raise serotonin levels" as many have come to believe, but rather
       | change the dynamics of serotonin in the brain. This produces
       | downstream changes that, over time, can contribute to lessening
       | depressive symptoms in some patients.
       | 
       | This makes more sense if you think about other conditions like
       | chronic pain. Someone suffering from chronic pain doesn't have an
       | "endogenous opioid deficiency". They're just in pain. Opioids are
       | one medication we can use to modulate their pain.
       | 
       | Unfortunately, the pop-culture misunderstandings about "low
       | serotonin" can mislead a lot of people into thinking that
       | research like this debunks SSRIs. It doesn't. As I said above,
       | we've known for decades that something else is going on. This
       | isn't actually a surprise to anyone in the field.
        
         | petesergeant wrote:
         | > the pop-culture misunderstandings about "low serotonin"
         | 
         | Let's be clear though, I had an actual licensed psychiatrist
         | say this to me last week. It's not like people are getting this
         | "pop-culture" information via blog articles...
        
           | dymk wrote:
           | It's possible the psychiatrist is using "low serotonin" as a
           | simple shorthand meant for the layperson
        
             | readthenotes1 wrote:
             | Sort of like saying "you'll do better in the new
             | compensation plan," "masks don't work", "masks do work", or
             | "I will mislead you because either I'm incompetent or
             | because you can't handle the truth. Either way, trust my
             | 'Science'"
             | 
             | I e., Bullshit. Not the level of communication I would want
             | with someone who is pretending to help me.
        
             | techdragon wrote:
             | Or like many practicing medical professionals in many
             | specialties where the patient demand is high enough to fill
             | their week ... they don't have time to keep abreast of
             | current research in their field and since they aren't
             | required to, they just don't. There is usually some
             | required ongoing professional development but that is in no
             | way designed to ensure they keep up with current research
             | consensus, more that they don't continue doing things the
             | old way when we know about newer better ways.
        
               | JamesBarney wrote:
               | This psychiatrist is either an lazy, an idiot or using
               | shorthand.
               | 
               | Anyone who spent even in a couple hours reading about
               | depression (one of the most common ailments) in the last
               | decade knows that low serotonin is not the cause of
               | depression.
        
               | techdragon wrote:
               | I'd agree with your assessment. It was just an opportune
               | time to mention that they may not be familiar with recent
               | research results. But you're absolutely right, they
               | should know this one.
        
             | Veen wrote:
             | I had a medical doctor describe the benefits of SSRIs with:
             | "these pills will increase the happy chemicals in your
             | brain".
        
         | [deleted]
        
         | Mo3 wrote:
         | Funnily enough the one I used to take (Escitalopram) apparently
         | has been found to begin permanently altering brain function
         | after only a few hours of first ingestion. I was pretty happy
         | with it. No pun intended
        
           | PragmaticPulp wrote:
           | Source? Im not aware of research that shows "permanent"
           | alterations from a single dose, unless someone is really
           | stretching the definition of "permanent"
           | 
           | Pointing to alterations isn't really helpful without context.
           | An anti-depressant should induce long-term helpful
           | alterations in order to alleviate symptoms.
        
             | Mo3 wrote:
             | https://www.mpg.de/8426203/escitalopram-brain
        
           | ratww wrote:
           | Also a happy customer of that one. It worked great for me
           | even with a low dosage and didn't otherwise negatively impact
           | anything else.
        
             | coffee_beqn wrote:
             | How long were you on and what made you go off it? Four
             | months in I'm feeling better now but I don't think I want
             | to take it forever
        
               | ratww wrote:
               | For me it was around the same time Mo3 mentioned they
               | took, maybe a bit more than one year and a half. It's
               | been long, so I don't remember precisely.
               | 
               | However I was in a quite sorry state before... I was
               | having several panic attacks a week. My therapy alone was
               | also not working well, I was doing twice a week. After
               | starting it, everything started falling into place. I
               | never had a panic attack again.
               | 
               | I never had any downside whatsoever from taking them
               | (didn't know they don't go well with summer!), including
               | the regular complaints, it wasn't really a burden on me
               | other than having to buy them monthly and take them every
               | day.
        
               | janeerie wrote:
               | I would like to see more discussion of the role of SSRIs
               | in treating anxiety, rather than depression (which always
               | seems to be the default focus). I also suffered from
               | panic that went away completely with SSRIs. I have never
               | had issues with depression, but these medications gave me
               | my life back.
        
               | ratww wrote:
               | Interestingly the reasoning from my doctor for me taking
               | Escitalopram was that it was good for anxiety, so I guess
               | there's at least some anecdotal evidence from doctors
               | about its efficacy...
        
               | Mo3 wrote:
               | Not comment OP but I got off recently after about 1.5
               | years - still very happy :) Although admittedly I did
               | have some infrequent spouts of rebound symptoms for a few
               | weeks, but those were pretty manageable.
               | 
               | Also, kind of happy to be off it right now honestly, heat
               | is something that doesn't go along well at all with
               | SSRIs.
        
         | spaceman_2020 wrote:
         | Sertraline suplementation wiped out depression almost
         | completely from my system within two months. I had been
         | depressed earlier for half a decade. Its been nearly 8 years
         | since I took sertraline (stopped within 3 months) and I haven't
         | had a depressive episode since.
        
           | agumonkey wrote:
           | Was your ailment caused by events ? or something that creeped
           | up invisibly ?
           | 
           | I'm often worried about neurochemical solutions if some part
           | of your brain is still associating events/memories/ideas with
           | pain.
        
         | jazzyjackson wrote:
         | > the pop-culture misunderstandings
         | 
         | You mean the TV commercials that played about 6 times per hour
         | in the 00s explaining that depression is caused by a chemical
         | imbalance ?
        
           | pessimizer wrote:
           | A pill with a smiley face.
        
         | carlmr wrote:
         | >SSRIs raise extra-synaptic serotonin levels within the first
         | hour of taking them. However, their efficacy against depression
         | takes weeks or even months to manifest. We've known this for
         | decades, and as a result the "chemical imbalance" theory of
         | depression hasn't been a real contender in depression research
         | for a long, long time.
         | 
         | This for me doesn't seem logical. It could be that a long term
         | imbalance makes you depressed, and reverting that imbalance
         | takes time to affect the thought processes towards the
         | positive. Only because the reaction is delayed, it doesn't mean
         | it's not causal.
        
           | malfist wrote:
           | There's a lot of evidence around hippocampus size in
           | depressed patients. They tend to be smaller than average.
           | After 6 months to a year of treatment with antidepressants
           | the hippocampus grows to a larger size.
           | 
           | It's speculated that hippocampus size might be one of the
           | driving components of depression, but who knows. Mental
           | illness is complex.
        
         | tsimionescu wrote:
         | > Unfortunately, the pop-culture misunderstandings about "low
         | serotonin" can mislead a lot of people into thinking that
         | research like this debunks SSRIs. It doesn't. As I said above,
         | we've known for decades that something else is going on. This
         | isn't actually a surprise to anyone in the field.
         | 
         | The article itself quotes one of the authors of the study, who
         | is attending medical school in psychiatry, as starting that his
         | training explicitly made this claim, that his textbooks make
         | this claim, and that he himself was later passing it down to
         | other students.
         | 
         | Other sources quoted by the news article are similar to your
         | own claims. Overall, it sounds like there are camps in
         | psychiatry that have indeed long abandoned this theory, but
         | others who still hold onto it.
         | 
         | Furthermore, the meta analysis being talked about in the
         | article _does_ make the additional claim that SSRIs are perhaps
         | not necessary for the treatment of depression. I don 't believe
         | they are right, but it's also misleading to suggest that theur
         | research is entirely in line with psychiatric orthodoxy.
        
           | PragmaticPulp wrote:
           | To be clear: The serotonin deficiency hypothesis has been
           | floated for a long time as _one of_ the possible underlying
           | changes involved in depression etiology. It's not even a
           | stretch, given that we can find upregulations of the
           | serotonin transporter in response to chronic unpredictable
           | mild stress, the fact that 5-HTP (serotonin precursors)
           | supplementation can boost mood, and the fact that many drugs
           | of abuse operate through serotonin receptors to alter mood.
           | 
           | However, like I said in my post above, we've know for decades
           | that it's not _the_ explanation because SSRIs boost
           | extrasynaptic serotonin levels within hours but their
           | therapeutic efficacy is famously delayed by weeks.
           | 
           | I suppose it's possible that the author had some weird
           | textbook that misrepresented the state of research, or that
           | he misunderstood the relative confidence and significant of
           | each theory presented. However, the state of research didn't
           | even believe that the serotonin hypothesis of depression was
           | the full, accurate explanation when SSRIs were introduced for
           | the reasons I stated above and more.
        
             | hn8305823 wrote:
             | I've tried lots of natural anti-depressant remedies.
             | Background: I've suffered with major depression my entire
             | life with frequent suicidal ideation and several near-
             | suicides. It's fairly seasonal and wile it happens
             | throughout the year the worst time is in the winter near
             | the solstice. I've also struggled with difficulty falling
             | asleep since very young childhood, though that has gotten
             | somewhat better with age (over 50 now).
             | 
             | ** warning ** If you are on any prescription anti-
             | depressants, don't stop taking them or modify your routine
             | without talking to your doctor first.
             | 
             | 5-HTP: nasty side effects from unwanted metabolism in the
             | gut and excess serotonin levels in the brain that border on
             | serotonin syndrome sometimes. After the initial 8 hours or
             | so of bad side effects the anti-depressant effects last for
             | about two days followed by a very hard crash on day 3.
             | During the 2 "good" days the quality of the effect is a bit
             | "off" and gives me an unusually "comfortable feeling" that
             | is while much better than depression is not the most
             | productive or normal feeling (see melatonin below for
             | contrast). Be extremely careful with 5-HTP, serious
             | serotonin syndrome can easily develop, especially if you
             | are on other anti-depressants and can be fatal. I don't
             | take 5-HTP anymore because of these side effects and better
             | options (below).
             | 
             | THC: Very effective during use (edibles = 4-6 hours), but
             | tolerance levels build requiring higher doses. mild anti-
             | depressant effects trail off gradually after day or two and
             | quality is generally good. Of course cannabis has some side
             | effects: short term memory impairment, general slight
             | cognitive reduction but I have found these side effects can
             | be virtually eliminated with L-Dopa (see below)
             | 
             | L-Dopa: Taken with vitamin B-6, this is one of the few
             | things I have found that enhances the cannabis experience
             | rather than taking away from it. This increases dopamine
             | levels in the brain which enhances the high and for me also
             | seems to miraculously eliminate the side effects of
             | cannabis (maybe this is due to offsetting dopamine
             | depletion by THC?). I have also found that L-Dopa even
             | seems to increase general cognitive functioning beyond
             | undoing the effects of THC (maybe reversing age related
             | degredation? It makes my brain feel like it did when I was
             | 18). L-Dopa does have serious side effects however: It
             | dramatically and seriously increases anxiety/paranoia for
             | several hours so I only take it with cannabis edibles and
             | even then not every time, no more than once per week. It's
             | very important to know how to manage paranoia since THC
             | also frequently triggers paranoia and the L-Dopa seems to
             | amplify that. My method is to consciously and affirmatively
             | "acknowledge and disregard" any paranoid or anxiety related
             | thoughts. I have found that once I consciously identify and
             | acknowledge certain thoughts are _caused_ by the drugs
             | /supplements and are not real (or as important as they
             | seem), they disappear and everything is ok.
             | 
             | Melatonin: This is by far the best anti-depressant I have
             | ever used. Essentially no side effects other than putting
             | you to sleep 30 mins after use, which when taken before bed
             | is a huge plus (I have had difficulty falling asleep my
             | entire life). Anti-depressant effects last for a few days,
             | gradually trailing off without the hard crash of 5-HTP. The
             | quality of the effect is also excellent (much better than
             | 5-HTP). The best way I can describe it is "feeling healthy,
             | energetic yet relaxed, and normal" most of the time. It's
             | like a miracle drug, at least for me. I take 5mg every 3-4
             | days as needed.
        
               | Throwaway45htp wrote:
               | Thanks for your post, and thanks for whoever vouched for
               | this. I have a similar background to you, including age,
               | living in a northern latitude with short winter days,
               | long term sleep issues, and suicidal ideation.
               | 
               | 5-HTP - There seems to be wide variation in the
               | formulations available from manufacturers. Some have
               | given me no issues at all, another brand, of the same
               | strength, consistently leads to intense nausea and
               | vomiting, followed by a significantly altered mental
               | state. Almost tripping, and yes, I'm familiar with that.
               | 
               | THC - agree with your comments, but by far the biggest
               | advantage for me is that it enabled me to completely quit
               | drinking. Alcohol is terrible in that it will temporarily
               | shut those intrusive thoughts off, but then they seem
               | supercharged them when they inevitably return after a few
               | hours. Drinking definitely exacerbates my actual
               | depression even if it masks some symptoms.
               | 
               | I do use melatonin occasionally/as required but not super
               | often. It's very effective as a sleep aid, but I have not
               | noticed any antidepressive effects in myself. Valerian is
               | also an extremely effective sleep aid for me. Will have
               | to research L-Dopa.
               | 
               | Consider trying Sceletium Tortuosum extract (Kanna). It
               | has been commercialized as "Zembrin" and is available in
               | OTC supplements. There are peer-reviewed studies
               | indicating that it is safe and effective, and personally,
               | I've found it to noticeably effective against anxiety,
               | less so for depression. As supplements go, it's
               | inexpensive.
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124331/
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828542/
               | 
               | Finally, psilocybin has been revolutionary for managing
               | my mental health, and specifically depression. I found
               | microdosing to be ineffective. A full trip sets me right
               | for several weeks, to the point where it is startling
               | when the intrusive thoughts start up again.
        
             | cwkoss wrote:
             | I've heard people say that the serotonin deficiency
             | hypothesis was invented by drug companies rather than
             | academics. Is that true?
        
         | marincounty wrote:
         | I'm pretty sure I'm hell banned, but forget about all the
         | chemicals of the brain.
         | 
         | Read anything by Irving Kirsch.
         | 
         | He used The Freedom of Information Act to study All the
         | antidepressants studies that were sent to the FDA by the pill
         | pushers, Not just the cherry picked studies, but All.
         | 
         | He found they basically don't work better than Placebo.
         | 
         | Personally, I think the "Happy" drugs have been the biggest con
         | job the American suffering have ever endured. At least we know
         | opioids work--for awhile. Antidepesssnts just make Dr. Wealthy
         | more wealthy.
         | 
         | My hope is most of these wonder drugs are sued into history,
         | along with those mandatory doctor office visits.
         | 
         | Ask yourself this--why do Psychiatrists have the highest rate
         | of suicide if these drugs work?
         | 
         | I'm glad we have residents whom picked an easy speciality upon
         | graduation, but these drugs have such low efficy rates they
         | should be illegal, or over the counter, with the exception of a
         | few. Trazadone can be nasty. A bad reaction is cured by a
         | needle to the middle part of the brain.
         | 
         | Most are easy on the body, but don't do anything besides make
         | an Artist (Medicine is an art, and Psychiatrists are the
         | milking to the bone.) wealthy.
         | 
         | God help our suffering Americans.
        
           | skjoldr wrote:
           | You shouldn't talk about drugs you have zero experience with
           | either as a doctor or as a patient. SSRIs do work.
        
             | epups wrote:
             | Only for severe depression, if you take into account all
             | clinical trials - including the ones buried by pharma
             | companies. This is the work by Irving Kirsch being
             | referenced here, and it's excellent.
        
               | butlerm wrote:
               | Spraying water on your house usually doesn't accomplish
               | very much unless your house is on fire. But if your house
               | really is on fire, it is likely the only thing that
               | works.
        
         | bergenty wrote:
         | I think you're throwing the baby out with the bath water here.
         | Sure depression may not be linked to low serotonin levels but
         | it almost certainly some chemical imbalance of some variety.
        
           | niemal_dev wrote:
           | Perhaps it's not a literal imbalance but more of a flow
           | problem, neural pathways fail to deliver and a portion is
           | lost along the way. There are so many ways this could be
           | going wrong, we have absolutely no clue unless we devise
           | proper tools and methodology for data-mining everything up to
           | a satisfyingly objective level.
        
           | bencollier49 wrote:
           | Metabolism and stress hormones both seem to play a role. It's
           | going to be a very complex thing - the best treatment for a
           | lot of brain conditions is just exercise.
        
             | belorn wrote:
             | The key word when using exercise to treat stress is that it
             | need to be voluntary (ie, something that the person want to
             | do). Forcing oneself to exercise has the opposite result
             | with increased corticosterone levels. Exercise is great if
             | and only if the individual is doing something they enjoy.
        
           | sneak wrote:
           | That's vague enough to be a totally useless description.
           | Dehydration is also a "chemical imbalance of some variety".
        
             | bergenty wrote:
             | I think that's part of the point. Whatever it is, it's a
             | chemical imbalance. Just need to find which one. In the
             | case of dehydration it's water.
        
               | s1artibartfast wrote:
               | I think the point is anything can be a chemical process
               | because we are chemical beings.
               | 
               | Drowning or having your leg cut off leads to a chemical
               | imbalance, but chemistry isn't always the most productive
               | lens to analyze the problem
        
               | bergenty wrote:
               | Drowning or having your leg cut off are not chronic
               | conditions. I think it makes a lot of sense to analyze
               | chronic problems in the brain through the chemical lens.
        
               | s1artibartfast wrote:
               | >I think it makes a lot of sense to analyze chronic
               | problems in the brain through the chemical lens.
               | 
               | Thats the basically the point I am taking issue with.
               | Myopic focus on chemistry can be terribly misleading.
               | There will always be a chemical component because we are
               | beings made up of chemical components.
               | 
               | a chemical imbalance is by definition always going to be
               | part of the problem. That does not mean it is always the
               | best point of intervention, and certainly not the
               | exclusive focus when trying to understand the problem.
        
               | bergenty wrote:
               | There really isn't a lot more going on in there though
               | based on our current understanding of the brain. It's
               | neurons and synapses and all the neurotransmitters that
               | regulate it all. What exactly are you suggesting could be
               | the problem?
        
               | s1artibartfast wrote:
               | This is the perfect example of myopic thinking coming
               | from the chemical Focus
               | 
               | If your only tool is a hammer then every problem looks
               | like a nail.
               | 
               | The brain is a lot more than chemistry, and that's not
               | even looking at the human being and their interactions
               | with the environment.
               | 
               | there are patterns encoded in the structure and biology
               | of the brain. There are psychological feedback loops and
               | complicated interactions between a human and their
               | environment.
               | 
               | Saying it must be a chemical imbalance is akin to
               | debugging a malfunctioning computer and saying it must be
               | a signal error from a loose wire. It ignores programming
               | sending signals on those wires and it ignores the input
               | to the machine from the environment
        
           | kayodelycaon wrote:
           | Or chemical imbalance is the symptom, not the cause.
        
         | heavyset_go wrote:
         | To add to this, SSRI onset efficacy corresponds with the
         | downregulation of serotonin receptors in the brain. "Low
         | serotonin" isn't what's being treated or changed, but the
         | number of receptors and their activation rates. SSRIs can
         | reduce emotional lability, which makes sense when you figure
         | that downregulation and increased activation of serotonin
         | receptors is a relatively stable system compared to an
         | unmedicated brain with many receptors and widely fluxuating
         | activation rates and lowered activation periods as serotonin
         | gets recycled quickly without its transporter being inhibited.
        
           | valec wrote:
           | i think it corresponds most exactly with the desensitization
           | of dendritic autoreceptors
        
             | heavyset_go wrote:
             | Yeah, downregulation is one of the last steps in
             | desensitization.
        
         | zeckalpha wrote:
         | Hence the first S and the I in SSRI. A filter in certain areas
         | increases other areas. Doesn't change overall values.
        
           | PragmaticPulp wrote:
           | I'm not sure what you're suggesting, but SSRIs definitely do
           | change a number of measurable metrics of the serotonin system
           | by prolonging the duration of serotonin in the extrasynaptic
           | space. This is well studied.
           | 
           | The first "S" is for selective, meaning they have minimal
           | affinities beyond the serotonin transporter.
        
             | zeckalpha wrote:
             | I don't think we're disagreeing. Increasing duration spent
             | in one place doesn't change the total count of the
             | molecule. SSRIs don't make the body produce more. That's
             | okay, they work by other means.
        
             | eurasiantiger wrote:
             | Where do you get that from? SSRIs act on SERT and SERT
             | handles reuptake from the synaptic cleft, not from
             | extracellular space which is "vacuumed" by MAOA/B and COMT.
        
           | arsome wrote:
           | The S for Selective actually means it _only_ works on
           | serotonin, compared with say, an SNRI, which works on both
           | serotonin and norepinephrine. Impacting the overall values is
           | in fact pretty much the only thing it does.
        
             | eurasiantiger wrote:
             | This is true, but inaccurate, as it only accounts for the
             | direct effects.
             | 
             | However, increased serotonin receptor agonism also
             | increases downstream dopamine and norepinephrine release.
        
             | zeckalpha wrote:
             | SRIs are a separate class of drugs: https://en.m.wikipedia.
             | org/wiki/Serotonin_reuptake_inhibitor
        
       | ComputerCat wrote:
       | I can't access the full text but this is really interesting. I
       | think with how fast paced all the advancements in the scientific
       | community are it's crucial that things we thought we understood
       | are continuously re-assessed and analyzed.
        
       | am63517 wrote:
        
       | fragcula wrote:
       | > Other clinicians say, however, that the notion of depression
       | being because of a simple chemical imbalance is outmoded anyway,
       | and that antidepressants remain a useful option for patients
       | alongside other approaches including talking therapies.
       | 
       | This is the key line in the summary.
       | 
       | The concept of attacking an idea no one really believes is really
       | a straw man.
       | 
       | More importantly the modern practice of medicine is "evidence
       | based medicine", not "mechanism based medicine". That means
       | treatments are tested as to _if_ they work, not _how_ they work.
       | Ideally in multiple well run double blinded randomised controlled
       | trials with at least some against treatment as usual. Unlike the
       | past when we thought more about _how_ they might work, theorising
       | something is off about someone 's humors and adjusting with
       | leeches.
       | 
       | Anyone looking for a truly mind bending result should look at
       | Hjorth et al. 2021 [0], the study recruited people with social
       | phobia and gave them all an SSRI (escitalopram). Half were told
       | they were getting a sham active placebo and "should not expect to
       | get better", half were told "you're getting the known effective
       | treatment".
       | 
       | Headline result being told you are being treated leads to 4x as
       | much response _with brain changes_ in the dopamin networks.
       | 
       | In the meanwhile, rather than worry about how antidepressants
       | work, why not take a look at electroconvulsive therapy which has
       | proven time and again to be the most effective treatment for
       | depression. Yet we have no idea how it works, other than knowing
       | a decent seizure in those without epilepsy makes you less sad?
       | What on earth.
       | 
       | [0] https://www.nature.com/articles/s41398-021-01682-3
        
         | ZeroGravitas wrote:
         | I don't think that's an accurate summary of the state of the
         | art on ECT:
         | 
         | https://www.nice.org.uk/guidance/ng222/chapter/Recommendatio...
         | 
         | It sometimes works, it's contraindicated for certain people,
         | comes near the end of the list of things to try (wait to see if
         | you get better and get some excercise/sleep/sunlight being low
         | risk interventions for mild depression) and even when it is
         | used and does work, starting/continuing antidepressants and
         | other treatments is recommended.
         | 
         | It's just one more tool in an incomplete and inconsistent
         | toolbox, not 1 weird trick your pharma company hates.
         | 
         | I know of one person who recently had some success with it, but
         | they tried other things first.
        
           | fragcula wrote:
           | I'm not sure what part of what I said you disagree with.
           | 
           | Nothing in the NICE guidelines explains how ECT works -
           | because like the rest of the world NICE does not know.
           | 
           | Once odd aspect with ECT is that it seems to transiently
           | improve parkinson's, again no one knows why.
        
             | ZeroGravitas wrote:
             | I was disagreeing specifically with this bit:
             | 
             | > electroconvulsive therapy which has proven time and again
             | to be the most effective treatment for depression
             | 
             | Switch "the most" for "an" and we agree I think.
        
         | openplatypus wrote:
         | IMO key quote the study you referenced:
         | 
         | > In conclusion, the anti-anxiety properties of SSRIs appear to
         | be largely dependent on expectancy effects on dopamine
         | signaling while SERT blockade is not sufficient for symptom
         | remission.
         | 
         | Drug works, if you believe it does :)
        
           | kokey wrote:
           | I wouldn't be surprised about this when it comes to panic
           | disorder. Just knowing you have some emergency fast acting
           | anti anxiety medication nearby, just in case you need it, can
           | reduce the number of panic attacks. There's probably all
           | kinds of psychological feedback loops when people have
           | anxiety about anxiety and then it escalates because they're
           | anxious about it escalating. I am guessing that medication
           | can help mitigate some components of that feedback loop for
           | some people.
        
             | guggalugalug wrote:
             | See also, David Foster Wallace's character David Cusk in
             | 'The Pale King'. A wonderful portrayal of how attending to
             | ANTs (Automatic Negative Thoughts) catalyzes this feedback
             | loop.
        
           | fragcula wrote:
           | It's a shame that the imagining is so expensive, because I'd
           | love to see a true control arm with placebos and follow up
           | scans.
           | 
           | i.e. if you are on a placebo and are told you will get better
           | how many do?
        
             | daniel_iversen wrote:
             | Don't they do truckloads of tests and comparisons on anti
             | depression medicine all the time including blind trials
             | etc?
        
               | fragcula wrote:
               | The interesting bits, for me, are the imaging scans which
               | are expensive and slow and you need more than one for
               | comparison per subject.
               | 
               | Secondly the 'covert treatment' aspect, and as far as I
               | know only Hjorth et al. do in any reasonable numbers is
               | the giving someone the treatment and usual and tell them
               | it's a placebo and they "shouldn't expect to get better".
               | 
               | It's ethically tricky to do that with an anxiety disorder
               | but I imagine a doctor telling someone with depression
               | that will be painfully close to "you're not getting
               | better", "we're not going to help you" and other quite
               | rejecting disheartening ideas.
               | 
               | But plain placebo controlled SSRI trials I think show
               | about a 0.2 absolute benefit in SSRIs in depression. i.e.
               | if you compare SSRI with placebo you need to treat 5
               | people with SSRI to see one more person respond. If you
               | compare SSRI with no treatment, you only need to treat 3
               | people with depression, to have 1 more respond. Those 3
               | and 5 are called the 'number needed to treat' and can be
               | compared to the 'number needed to harm'.
        
           | davidy123 wrote:
           | The drug does something. It at least creates a distraction.
           | That distraction can create a helpful feedback loop. After
           | all, depressive/anxious/etc thoughts are generally arbitrary
           | (though relentness), out of the all the thoughts one could
           | have. So a chemical causing an effect, or just the process of
           | trying an intervention can be useful. Distraction is
           | incredibly important in therapy, it is after all ultimately
           | how we all deal with the fact our lives have an end.
        
         | sinecure wrote:
         | Belief dictates reality. This is the fundamental driver behind
         | the common effectiveness of placebo. Which leads to the
         | question, does depression exist as a flaw in the brain? A
         | malfunction? Or is it like a mind virus, that it becomes an
         | inescapable suffering because we are told we are broken and
         | powerless to fight these feelings?
         | 
         | If a person is feeling sad, often, and without reason, and you
         | tell them "Sorry, your brain is broken, you have depression, we
         | will give you these pills to fix your brain chemistry." You
         | have taken that person's autonomy away. They are now the victim
         | of a disease.
         | 
         | I think the reality is that our society and civilization leads
         | to a certain despair and sadness in many people, one that can
         | be fixed by changing one's lifestyle, mindset, or overcoming
         | challenges. This is not a disease, not a mental illness, not
         | some health problem you cure with a pill. It's a spiritual
         | dilemma that must be faced individually and overcome with
         | effort and belief that one can change.
         | 
         | Essentially, I believe that by diagnosing people with "clinical
         | depression" we are creating a self fulfilling prophecy and
         | condemning them to a victim status that perpetuates their
         | suffering.
        
         | s1artibartfast wrote:
         | >That means treatments are tested as to if they work, not how
         | they work. Ideally in multiple well run double blinded
         | randomised controlled trials with at least some against
         | treatment
         | 
         | There are some concerning departures from this with medical
         | approvals based not on treatment, but biomarkers.
         | 
         | Without getting too political, two noteworthy recent examples
         | come to mind. The first is abelacimab for alzheimer's, approved
         | based on plaque, not disease progression.
         | 
         | The other is juvenile covid vaccines, approved based on
         | antibody presence.
        
           | fragcula wrote:
           | abelacimab in particular was quite worrying. The BMJ (the
           | journal OP posted) contained a criticism of that.
           | 
           | Similarly as you say is that because numbers are easy to
           | think about antibody titres somehow took over the world when
           | it came to covid vaccination. Despite good evidence t-cell
           | activity is important for preventing severe disease.
        
         | varispeed wrote:
         | > are tested as to if they work, not how they work
         | 
         | Should they be doing both? I can't imagine shipping code that I
         | don't know how it works, but it passes tests...
         | 
         | Otherwise, you'll get pseudoscience - just mix random chemicals
         | and see how patient reacts, rinse and repeat until something
         | works...
        
           | workingon wrote:
           | Welcome to modern medicine.
        
           | kurikuri wrote:
           | >Should they be doing both?
           | 
           | Yes, but with different aims. The learning about 'how a
           | treatment works' is useful for developing new potential
           | treatments and new hypotheses, but the mechanism itself is
           | not necessary nor sufficient in its potential treatment
           | efficacy.
        
           | boesboes wrote:
           | > shipping code that I don't know how it works, but it passes
           | tests
           | 
           | We call that machine learning
        
             | rmbyrro wrote:
             | What isn't machine learning is sometimes called "tested
             | code"
        
           | fragcula wrote:
           | The psychiatrists themselves don't need to do both, as
           | doctors practicing EBM they are interested in proven results.
           | The decision to recommend a treatment (and to accept it) is
           | based on the pros and cons only.
           | 
           | What people really care about is side effects. That's one of
           | the reasons modern pharmas are so fixated in testing old
           | drugs for new disorders (the other reason is they might be
           | able to get a new patent case in point when Eli Lilly made
           | pink fluoxetine for girls with a new indication for PMS [0]).
           | 
           | Similarly, the best way to identify side effects is by
           | looking at the molecule and guessing (static analysis),
           | testing with cells, animals or other non-human biological
           | systems (I guess this is alpha testing as we rarely think of
           | the testers as human...), and then in human studies (early
           | access).
           | 
           | Even then we roll out incrementally (phase 2), before widely
           | testing in phase 3 and collecting feedback.
           | 
           | [0] https://money.cnn.com/2000/07/06/companies/lilly/
        
           | vkou wrote:
           | > Should they be doing both? I can't imagine shipping code
           | that I don't know how it works, but it passes tests...
           | 
           | If that were the criteria, then we would not have medicine at
           | all, because biological systems are so incredibly
           | complicated, nobody understands even a tiny fraction of _how_
           | a particular chemical will affect them.
        
             | harshreality wrote:
             | I don't think that's quite accurate. We know first-order
             | biochemical effects for a lot of drugs. There are always
             | side effects, but they're _side-_ effects, and those are
             | largely understood as well.
             | 
             | Psych drugs have difficulties because they aren't used for
             | their biochemical effects, they're used for their
             | psychological effects, and psychological effects of
             | biochemical processes are poorly understood.
        
               | fragcula wrote:
               | An extra foible is that many medications have psychiatric
               | side effects.
               | 
               | So even if you're prescribed a statin for the biochemical
               | effect on cholesterol you might get some of the purported
               | psychiatric effects.
        
         | pineaux wrote:
         | Most effective treatment for depression = psychedelics. They
         | have been used by shamans for eons for this reason. A lot of
         | modern research into this (including 1000s of research studies
         | from the 50s and 60s) confirms it. It was only because Nixon
         | didn't like the fact that kids were not going to war, that the
         | war on drugs was started.
        
           | tsol wrote:
           | Not everyone wants to trip in order to feel alright, and not
           | everyone can handle it. Children and the elderly come to mind
        
             | multiplegeorges wrote:
             | When used for treatment, you don't "trip" in the
             | recreational sense.
             | 
             | The medication is taken in a very controlled environment
             | with a highly trained mental health professional.
             | 
             | There are also pre- and post-sessions to help people
             | prepare for the experience and come out from it with
             | positive outcomes.
             | 
             | Agreed that children probably shouldn't be given such
             | strong drugs. I don't think you'd find a professional
             | advocating for that.
             | 
             | As for the elderly, the drugs have been used in near-death
             | therapy with elderly terminal patients. It has helped
             | people overcome their fear and anxiety around dying and
             | come to terms with their situation in a peaceful way.
        
               | olyjohn wrote:
               | It's just too bad that most people can't get access to
               | this treatment. It's extremely difficult to get into, and
               | impossible for most people.
        
           | MrDresden wrote:
           | Psilocybin has done wonders for my anxiety and depression in
           | the past.
        
           | DFHippie wrote:
           | > It was only because Nixon didn't like the fact that kids
           | were not going to war, that the war on drugs was started.
           | 
           | Was it this or that he saw asserting dominance over youth
           | culture as a political winner? Judging from the present
           | moment, bullying the less powerful seems to have a lot of
           | political juice. People want to keep the uppities down.
        
           | sneak wrote:
           | Please do not assert pet theories as established scientific
           | consensus or fact.
        
             | pineconewarrior wrote:
             | Lack of citation does not make it a "pet theory".
             | 
             | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767816/
             | 
             | https://www.nature.com/articles/s41591-022-01744-z
             | 
             | Go search it before being rude
        
               | wkearney99 wrote:
               | Or, include the links yourself when making such claims?
               | Unsupported comments are perhaps just as rude?
        
           | meijer wrote:
           | Book recommendation: "How to Change Your Mind" (Michael
           | Pollan)
        
           | woevdbz wrote:
           | I'm not sure we know about the side effects very well yet
           | though?
        
         | webmobdev wrote:
         | > _why not take a look at electroconvulsive therapy_ ... _Yet
         | we have no idea how it works_ ...
         | 
         | Or you can stick with something that has been already been
         | scientifically studied and proven to be as effective as anti-
         | depressants in curing depression - Cognitive Therapy. In fact,
         | it even prevents relapses more than anti-depressants:
         | 
         | > Depression is one of the most prevalent and debilitating of
         | the psychiatric disorders. Studies have shown that cognitive
         | therapy is as efficacious as antidepressant medications at
         | treating depression, and it seems to reduce the risk of relapse
         | even after its discontinuation. -
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748674/
         | 
         | For those considering going to a CT therapist you can search
         | for certified CT therapist from here:
         | https://cares.beckinstitute.org/get-treatment/clinician-dire...
         | (the Beck Institute was started by the founder of CT and is now
         | run by his daughter who is also a professional in this field.
         | Nowadays most therapist learn about CT during the education but
         | only have the base knowledge of it and thus don't apply CT
         | techniques properly during therapy, and remain ignorant of the
         | advances in this field. Those who actually train and specialise
         | in it are more effective.)
        
           | Pigalowda wrote:
           | It's not an either/or scenario. CBT is recommended already
           | for pretty much all comers. ECT is last line in treatment
           | refractory MDD.
        
           | fragcula wrote:
           | We also don't know who CBT works for what it's worth.
           | 
           | It's also fairly limited in suitability (good luck with
           | someone with catatonic depression trying to get them do a hot
           | cross bun), availability (thankfully online therapies are
           | more common now, but it takes 2 mins a day to take a pill and
           | about an hour per week for CBT), affordability (a year of
           | sertraline will cost less than the initial session of session
           | of CBT can).
        
       | rozab wrote:
       | See also "Serotonin and Depression" from David Healy (2015)
       | 
       | https://www.bmj.com/content/350/bmj.h1771
       | 
       | https://davidhealy.org/so-long-and-thanks-for-all-the-seroto...
        
       | phkahler wrote:
       | Nobody checks your serotonin levels prior to prescribing an SSRI.
       | The drugs do help some people but the reality is that nobody
       | really understands how it all works.
        
       | walrus01 wrote:
       | I have a completely unscientific, subjective theory that some
       | significant portion of depression in the population as a whole is
       | caused by the economic circumstances that some people live in.
       | 
       | Things like being trapped in a dead end job to keep healthcare
       | benefits in the USA, living in a never ending treadmill of debt.
        
         | carabiner wrote:
         | IOW: Are you ready for me to diagnose your totally normal
         | reaction to our shitty society as mental illness so I can get
         | you addicted to mind altering drugs for the rest of your life?
         | https://imgur.com/Jb1mJyx
         | 
         | Or as the Unabomber said, "Imagine a society that subjects
         | people to conditions that make them terribly unhappy then gives
         | them the drugs to take away their unhappiness. Science fiction?
         | It is already happening to some extent in our own society.
         | Instead of removing the conditions that make people depressed
         | modern society gives them antidepressant drugs. In effect
         | antidepressants are a means of modifying an individual's
         | internal state in such a way as to enable him to tolerate
         | social conditions that he would otherwise find intolerable."
         | 
         | I think you're right. The problem is, this is the only life
         | most of us have lived, and so we cannot imagine it otherwise,
         | like a fish who cannot conceive of a world above water, or even
         | that water is the medium surrounding it. If our entire society
         | is causing this, then what can we do? Wage slavery, oligarchy,
         | attention theft by tech companies, disintegration of community
         | from various causes. Life for so many people is crawling
         | through glass Monday through Friday, then getting shitfaced on
         | the weekend. Is that happiness? How do we escape?
        
           | seventytwo wrote:
           | > Life for so many people is crawling through glass Monday
           | through Friday, then getting shitfaced on the weekend. Is
           | that happiness?
           | 
           | Ooof
        
           | grumple wrote:
           | Brave New World and 1984 were near-future fiction, but were
           | more near future than fiction. Drugs are soma.
        
           | tptacek wrote:
           | It's a strange mode of persuasion, making arguments about how
           | we should frame psychological dysfunction that quote a man
           | who pooped into a hole in the corner of a shack while in
           | hiding after trying to down a passenger jet.
        
             | eurasiantiger wrote:
             | That is the definition of an "ad hominem" argument.
        
               | tptacek wrote:
               | I'm comfortable with "ad hominem" when the appeal in
               | question is to the Unabomber.
        
               | carabiner wrote:
               | You wish to vilify him. That's fine. It's extremely
               | uncomfortable to find that this mathematician was right
               | about something. I respect your feelings. But that
               | doesn't alter the substance of his social critiques.
        
               | tptacek wrote:
               | Sure it does. It's strange to argue that it wouldn't.
               | Kaczynski is a madman, and perhaps the only person in the
               | history of the United States whose quality of life was
               | drastically improved by incarceration in a Supermax
               | prison.
        
               | inkblotuniverse wrote:
               | He lived out in the fresh air and sunlight.
        
               | tptacek wrote:
               | So do rats.
        
               | dathos wrote:
               | I doubt he would agree with that, just like depression
               | has many forms so does the concept of quality of life
        
             | paulmilligrams wrote:
             | Quoting the Unabomber was a strange choice considering the
             | main idea isn't unique to him and stands on its own merit:
             | 
             | "Instead of removing the conditions that make people
             | depressed modern society gives them antidepressant drugs."
             | 
             | Examining the social factors that contribute to pathology
             | isn't controversial nor does it downplay the role of drugs
             | in reducing harm.
        
           | tsimionescu wrote:
           | It's very funny to describe SSRIs or SNRIs essentially as
           | "happy pills". They are very unpleasant drugs to take,
           | especially in the first month or so when starting to use
           | them, and no one would be using them if they didn't feel
           | there is a serious problem in their lives.
           | 
           | Not to mention, depression takes several forms, and not all
           | of them are related to unhappiness. A common form is related
           | to anxiety, with people experiencing a constant feeling that
           | something awful is about to happen, sometimes getting
           | terrible panic attacks. Given that many of these people live
           | in objectively and subjectively extremely safe environments,
           | much safer than at any other time in history, it's very hard
           | to take seriously any environmental theory of this kind.
           | 
           | Edit: corrected one bad auto-correct typo ("problem", not
           | "purulente") .
        
             | imtringued wrote:
             | >no one would be using them if they didn't feel there is a
             | serious purulente in their lives.
             | 
             | You are playing into the argument, people often don't have
             | a choice to avoid a depression inducing environment, they
             | only have the choice of using drugs or not.
        
               | bmitc wrote:
               | Environment is only one component of certain types of
               | depression. It is primarily a biological phenomenon.
        
             | carabiner wrote:
             | Would you rather be safe in prison for 100 years, or free
             | in a world for 1 day where you could die?
        
               | olyjohn wrote:
               | Life isn't like that though. This question is kind of
               | counter-productive.
        
               | winocm wrote:
               | I prefer death.
        
               | tsimionescu wrote:
               | I know for sure that I have much more anxiety when I'm in
               | an unsafe environment than a safe one, regardless of how
               | free I am in each. Lack of freedom does lots of bad
               | things to your mind, but anxiety isn't one of them.
        
             | bmitc wrote:
             | This site has an unbelievable amount of armchair-science
             | that gets rattled off. You are right, because depression
             | and anxiety are primarily biological phenomena.
             | 
             | People looking for an actual expert discuss these things
             | should watch Robert Sapolsky's talk:
             | https://www.youtube.com/watch?v=NOAgplgTxfc
             | 
             | For example, in the talk, he points out one of the most
             | telltale signs of depression is waking up early, which is
             | completely backwards from the common perception that
             | depression is someone staying in bed all day.
        
         | imtringued wrote:
         | Actually there is something worse than a deadend job. Having a
         | job you are financially dependent on but where you aren't
         | assigned any work so you must constantly come up with ways to
         | look busy and productive.
        
         | yomkippur wrote:
         | There's rich people, famous people, powerful people, who fall
         | into depression so not sure what your situation is but I hope
         | you get through it.
        
         | missedthecue wrote:
         | All quintiles of the US population make more money (inflation
         | adjusted) than they did 20, 40 or 60 years ago.
         | 
         | Yet there are more depressives around than ever.
        
           | asdff wrote:
           | This inflation adjustment business needs adjusting I think if
           | you think the average worker today has more buying power than
           | they did in decades when they were actually buying homes.
        
           | inkblotuniverse wrote:
           | Yeah, nobody can afford a house.
        
             | imtringued wrote:
             | People constantly shout how property values would go down
             | if people could afford homes.
        
           | quickthrower2 wrote:
           | Inflation measurement is a political tool.
        
           | actually_a_dog wrote:
           | Now look at what it gets spent on. Specifically, take a
           | closer look at housing, healthcare and higher education. All
           | three of those have risen far, far faster than inflation for
           | many years.
        
         | Taylor_OD wrote:
         | I'm overall pretty happy and have a pretty great job, life, and
         | family. I'm still often hit with waves of despair when I
         | realize housing prices are insane, retirement feels like a
         | joke, and the biggest issues the world is facing seem to be
         | ignored.
         | 
         | It's pretty depressing if you dwell on it for any period of
         | time.
        
         | asdff wrote:
         | You don't even have to be broke to be trapped in the
         | stranglehold of modern society and feel like shit about it.
         | Just because you are paid well doesn't mean the work you are
         | doing is remotely engaging or interesting or doesn't want to
         | make you hate yourself. Being rich doesn't insulate you from
         | toxic coworkers, in fact probably the higher you end up
         | marching up the economic ladder the more of these narcissistic
         | and toxic personalities you are liable to run into.
         | 
         | At the end of the day we are probably happiest when we are
         | foraging for berries or mushrooms. This whole abstract
         | 'society' crap we put upon ourselves leads to a lot of self
         | directed scorn, embarassment, disrespect, and no doubt
         | depression. How many billions of calories have been burned to
         | fuel thoughts of worry about an outfit choice around the world?
         | How many grey hairs have sprung up as a result of fretting
         | about appearance? The stress society tries to shovel on you is
         | such a waste of energy and does nothing to help you.
        
           | autoexec wrote:
           | > How many billions of calories have been burned to fuel
           | thoughts of worry about an outfit choice around the
           | world?...The stress society tries to shovel on you is such a
           | waste of energy and does nothing to help you.
           | 
           | Sadly, not enough to offset our sedentary lifestyle and
           | diets. I can't be too concerned about the energy expenditure
           | involved in worrying about meaningless things. For now
           | anyway, we've got energy to spare. The toll of all that
           | stress on our bodies is much worse than the calories we lose.
           | Still, I'd rather be worried about the trivial things that we
           | occupy ourselves with than the life or death worries humans
           | regularly faced when we were berry foragers. Going from
           | worrying over "Will we eat today?" to "Which of several
           | restaurants should we go to for lunch?" is a blessing.
        
         | triyambakam wrote:
         | I'm puzzled by those who disagree with this statement. How is
         | it surprising that depressing circumstances would lead to
         | depression?
        
           | astrange wrote:
           | Major depressive disorder isn't the same thing as feeling sad
           | about your job.
        
             | psyc wrote:
             | If being down about your job causes symptoms of depression
             | that last more than 2 weeks, then it's the same thing.
             | Psychiatrists diagnose based on symptoms. Worse, its
             | usually what you say your symptoms are, with words and
             | talking. They don't scan your brain. I've been seeing
             | psychiatrists for almost 30 years. The good ones take
             | plenty of interest in your situation, lifestyle, and other
             | non-chemical non-medical factors. Psychiatrists don't
             | distinguish between so-called 'situational' and 'clinical'
             | depressions. Laypeople do that. If you get diagnosed by a
             | _clinician_ , _that_ is the part that makes it clinical -
             | it isn 't a different kind of condition.
        
             | an-honest-moose wrote:
             | That is an incredibly dismissive and reductive argument to
             | make. "Feeling sad about your job" isn't limited to burnt
             | out software engineers with a safety net. It can also apply
             | to, for example, someone stuck in a shitty, low paying job
             | with few, if any, prospects for better employment. The lack
             | of a path to a decent future can, in itself, be incredibly
             | demoralizing, even if your present circumstances might be
             | decent. After all, what's the point in continuing if I can
             | see that it's all downhill from here?
        
               | astrange wrote:
               | That isn't major depressive disorder either. Even if
               | those people think their life sucks, they're capable of,
               | say, getting out of bed every day and don't regularly
               | attempt suicide.
               | 
               | Russian serfs might've revolted when they got the chance,
               | but they were more or less psychologically normal until
               | then. Their society adapts to not kill them all. (Or they
               | all become alcoholics or something.)
        
             | UK-Al05 wrote:
             | Bad jobs can cause suicide
        
               | WalterSear wrote:
               | Suicide is usually due to distress than clinical
               | depression. This is why suicide hotlines work at all.
        
           | pcmoney wrote:
           | I would recommend reading some history books before saying
           | these are depressing circumstances.
        
             | asdff wrote:
             | Just because some people have suffered through worse
             | doesn't mean that you can use that to invalidate someone
             | else's suffering.
        
               | ThrowawayR2 wrote:
               | But when, for the vast majority of history, the
               | population faced a much poorer, more monotonous, and less
               | free existence than what the modern worker faces then you
               | jolly well can.
        
               | asdff wrote:
               | That still doesn't invalidate people's mental conditions
               | today.
        
               | pastacacioepepe wrote:
               | > the population faced a much poorer, more monotonous,
               | and less free existence
               | 
               | That's an over simplification.
               | 
               | People could still have more free time than we do now[1],
               | while their life could be more monotonous on some aspect,
               | I believe an average office worker life today can be even
               | more monotonous than what a serf life could be. You also
               | have to consider labor alienation, which is a something
               | that didn't exist so much before industrialization.
               | 
               | Most importantly, life commonly revolved around tight
               | communities, while today most people live in
               | individualist societies.
               | 
               | Individualism certainly has a larger impact on happiness
               | than most modern convenience has.
               | 
               | - [1]: https://groups.csail.mit.edu/mac/users/rauch/workt
               | ime/hours_...
        
               | ThrowawayR2 wrote:
               | If there are people today who want to put their money
               | where their mouth is and give up the conveniences of
               | modernity to go back to communal subsistence farming
               | under serf-like conditions (and there are places in the
               | world that still live like that), more power to them. I
               | haven't seen any takers.
        
               | pastacacioepepe wrote:
               | I don't understand this need to make everything white or
               | black, unless we want to pretend we live in a word as
               | simple as a kids' novel. You can't just throw away
               | milleniums of history and people because in the past 60
               | years we have become too lazy and addicted to modern
               | convenience.
               | 
               | No, preindustrial ages weren't the hell they're made to
               | be nor a golden age by any means. The same can be said of
               | today. Stop playing defensive and think openly instead,
               | there's lot we can improve by learning from the past.
        
         | sn0w_crash wrote:
         | I know plenty of depressed rich people. I understand your
         | theory but spend a week in the Hampton's and you'll see some
         | real sad souls.
        
           | [deleted]
        
           | gillytech wrote:
           | Yeah they are probably into some extremely toxic, unnatural
           | things that cause them to secretly hate themselves. I wonder
           | how much shady sexual shenanigans happens in the households
           | of the top 1%? Plenty of drugs, gossip, gluttony, lust, etc.
           | 
           | Happiness comes from the overcoming of not unknowable
           | obstacles toward a known goal. It's the journey, not the
           | destination. And the trick is to set another goal once you
           | attained the one you're on.
        
             | s-lambert wrote:
             | >Happiness comes from the overcoming of not unknowable
             | obstacles toward a known goal. It's the journey, not the
             | destination. And the trick is to set another goal once you
             | attained the one you're on.
             | 
             | I find this kind of bizarre because you can look around and
             | see how it's obviously not true. Dogs are happy as clams to
             | just socialize with their owners / other dogs and just
             | live. People hustling to always get to the next goal don't
             | seem particularly happier than people who don't have a goal
             | and just have a healthy social life.
        
               | gillytech wrote:
               | A. People aren't dogs. We are of a much higher level
               | intelligence and self awareness. That's why psychological
               | studies of rats, or even apes, as human analogs is
               | ludicrous.
               | 
               | B. The happiest people on the planet are extremely
               | ethical, have a good moral compass and have a will to
               | help others. They have goals and attain them. And they
               | especially don't blame their environment for their
               | shortcomings. They find ways to adjust their environment
               | to themselves and not the other way around.
               | 
               | Someone who is content with a simple life is still
               | following that maxim. Their goal is to live each day in
               | relative comfort according to their own standards.
        
             | walrus01 wrote:
             | > I wonder how much shady sexual shenanigans happens in the
             | households of the top 1%
             | 
             |  _Fidelio_
        
           | [deleted]
        
           | emodendroket wrote:
           | Plenty of people are very unhealthy despite ample access to
           | fluids. Nevertheless, it is very difficult to be healthy if
           | you don't have enough water.
        
         | pcmoney wrote:
         | We have it way better than almost any period in history and are
         | profoundly unhappy.
         | 
         | Also, we always like to think we will be happy "once I
         | have...X" and then we get X and say well actually what I need
         | is Y.
         | 
         | Most unhappiness is driven by vanity and desire (a bargain you
         | make with yourself where you chose to be unhappy until you get
         | something) to be better than our peers.
         | 
         | Until you can be content with nothing you wont be content even
         | with everything.
         | 
         | If people can be happy in concentration camps we can be happy
         | in dead end office jobs. They cant stop us from being happy.
        
           | kayamon wrote:
           | > If people can be happy in concentration camps we can be
           | happy in dead end office jobs.
           | 
           | I don't think people in concentration camps are happy.
        
             | carabiner wrote:
             | He's probably referring to the book Man's Search for
             | Meaning. The book's conclusion is a bit controversial for
             | this.
        
               | mercer wrote:
               | and Frankl, the writer, is rather controversial himself.
               | Personally, I can't take what that guy writes seriously.
        
           | taylorius wrote:
           | How are we measuring "better"? If suicide rates have risen
           | significantly, then perhaps there are ways in which our
           | modern paradise is worse than the past.
        
           | scns wrote:
           | This might help https://www.amazon.com/Happiness-Trap-
           | Struggling-Start-Livin...
        
           | WalterSear wrote:
           | This is an article about clinical depression, not
           | 'unhappiness'. While distress can result in clinical
           | depression, they aren't at all the same thing. One gets
           | better if the stressor is removed, the other does not.
        
         | refurb wrote:
         | I have a gardener. In fact, I have three gardeners. Three
         | generations of men with no ambition, who are happier than I
         | will ever be.
        
       | ernestoperez wrote:
       | Prof Montcrieff is Professor of Critical and Social Psychiatry. I
       | wonder how her patients are doing, if she currently has a
       | clinical practice.
        
       | yomkippur wrote:
       | Psilocybin has been quite promising and many people report
       | positive changes.
        
         | sammalloy wrote:
         | Came here to say this. Although few people are aware of it, it
         | is said behind closed doors that for some people, it is a cure
         | for depression, although it's very controversial to make that
         | claim in public, and obviously, it needs to be used carefully
         | and with great respect.
        
       | fredgrott wrote:
       | The problem with these studies is....
       | 
       | That they focus on one sub-system instead of how the sub-systems
       | interact together.
       | 
       | My bias, I solved my ADHD control problems by researching how
       | serotonin, dopamine, adenosine, ne, and cdb together regulate
       | both the increases and decreases in dopamine and all the
       | cofactors needed to increase dopamine production.
       | 
       | The move from one system to full systems based understanding in
       | the Biology and neurology space started in the 1970s as Chaos
       | theory took hold. But it takes awhile to become fully entrenched
       | in each science discipline.
       | 
       | One cannot say that serotonin by itself controls depression as
       | CBD is also involved! Runners know this as runners high is the
       | result of high CDB neurotransmitter levels!
       | 
       | Another fun fact, Cacao and Cocoa have anandamide which is the
       | THC-less way to get that runner high!
       | 
       | Sorry, was a Biology and Chemistry major once...I really cannot
       | get it out my system.
        
       | hestefisk wrote:
       | So does this mean SSRIs don't work?
        
       | [deleted]
        
       | ggm wrote:
       | My psychologist tells me that in his profession there is a
       | significant gulf emerging between the ones who feel the
       | prescribing is justified, and the ones (like him) with
       | significant concerns:
       | 
       | 1. they prescribe both boosters, and inhibitors, to treat the
       | same symptoms. This suggests the aetiology of disease here, is
       | not well defined by a single behaviour because the same symptom
       | (depression, anxiety) is responsive in some people to suppressing
       | of a chemical imbalance, and in others to boosting it.
       | 
       | 2. the drugs were tested inadequately across race, age, weight,
       | sex.
       | 
       | 3. the drugs appear to be best applied for as brief time as
       | possible but are routinely being prescribed for extended periods,
       | and demand de-habituation and great care with withdrawal
       | 
       | 4. almost all successful uses of the drugs are accompanied by CBT
       | and like processes.
        
         | PragmaticPulp wrote:
         | > 1. they prescribe both boosters, and inhibitors, to treat the
         | same symptoms. This suggests the aetiology of disease here, is
         | not well defined by a single behaviour because the same symptom
         | (depression, anxiety) is responsive in some people to
         | suppressing of a chemical imbalance, and in others to boosting
         | it.
         | 
         | "Chemical imbalance" isn't actually taught as the root cause of
         | depression. I suspect your psychologist might be overestimating
         | their own knowledge of a different field (psychiatrist formally
         | study these systems and medications, psychologists do not) and
         | underestimating the amount of research being performed in this
         | field.
         | 
         | Regardless, these drugs don't really work as "boosters" like
         | commonly thought. It's better to think of them as modulators.
         | In fact, in conditions like anxiety SSRIs are well-known to
         | actually reduce serotonin transmission in certain areas of the
         | brain. The research has diverged quite a bit from the simple
         | marketing-material models that a lot of people have about these
         | drugs.
         | 
         | The purpose of the drugs is to _induce changes_ that result in
         | positive downstream effects. It 's not actually a contradiction
         | that enhancing and inhibiting certain receptors could result in
         | similar downstream effects. For example, a number of receptors
         | in your brain will downregulate in response to both agonists
         | and antagonists, even though they have opposite direct effects.
         | Your psychologist's understanding of this topic is deeply
         | flawed.
         | 
         | > 2. the drugs were tested inadequately across race, age,
         | weight, sex.
         | 
         | SSRIs have been in widespread use since the 80s and tricyclics
         | since the 50s. At this point, the idea that we haven't tested
         | enough or that we haven't collected enough data is just a
         | strawman argument proposed by people with impossibly high
         | standards. I suspect no amount of testing would actually
         | satisfy someone proposing this argument for drugs that have
         | been studied for this long.
         | 
         | > 3. the drugs appear to be best applied for as brief time as
         | possible but are routinely being prescribed for extended
         | periods, and demand de-habituation and great care with
         | withdrawal
         | 
         | It doesn't make sense to make blanket statements about "the
         | drugs" when psychiatric drugs differ widely in this regard.
         | Benzodiazepines should absolutely be prescribed for brief
         | periods and this is reflected in their status as controlled
         | substances and all of the prescribing literature. There are
         | some doctors who ignore this advice and overprescribe, of
         | course, but they are going counter to standard practice.
         | 
         | On the other hand, medications like SSRIs can actually take
         | weeks or months to reach full effect and many patients
         | unnecessarily relapse by quitting them early.
         | 
         | I'd be cautious of taking advice from anyone who makes blanket
         | statements about "the drugs". This is bordering on uninformed
         | anti-psychiatry.
         | 
         | > 4. almost all successful uses of the drugs are accompanied by
         | CBT and like processes
         | 
         | The _most successful_ uses of SSRIs are accompanied by therapy.
         | However, we have plenty of studies where SSRIs are prescribed
         | without any accompanying therapy and a positive result is still
         | seen. If you 're suggesting that the therapy is actually doing
         | 100% of the work, that's easily disproven by the studies that
         | test all combination (placebo, therapy alone, SSRI alone,
         | therapy + SSRI).
         | 
         | I'd recommend getting your psychiatry advice from actual
         | psychiatrists. The number of misunderstandings and mistruths in
         | what you've relayed here is quite high.
        
           | ggm wrote:
           | I'm not a psychiatrist or psychologist. He is, and has
           | professional standing. You're judging him, on my paraphrases
           | of what is said to me. Perhaps what you really should be
           | saying is "don't try to represent the views of professionals
           | in a field you are not an expert in" which btw, I would take
           | as good advice.
           | 
           | None the less, I think the substantive point stands: the
           | field is not in unity about the applicability of these drugs,
           | and their use.
           | 
           | Do you disagree?
        
             | PragmaticPulp wrote:
             | > None the less, I think the substantive point stands: the
             | field is not in unity about the applicability of these
             | drugs, and their use.
             | 
             | Which field? You said he was a psychologist. Your post was
             | about psychiatry and neuroscience topics.
             | 
             | I don't disagree that psychologists have a lot of opinions,
             | but it's not really their domain. I think it's a mistake to
             | think that a psychologist is better educated on psychiatry
             | topics than actual psychiatrists or neuroscientists who
             | actually study these things and understand the research.
        
               | ggm wrote:
               | I think the gap between GPs, Psychologists and
               | Psychiatrists lies at the heart of this. GPs can (and do)
               | prescribe psychoactive drugs. What they do subsequently
               | is subject to the constraints of the health economics
               | which apply: In the UK (I am told) the delay to be seen
               | by anyone other than your GP can be measured in YEARS
               | because of the backlog in patents presenting. Many of
               | these patients are young people. The GP has the
               | determinant of the path. They can recommend something
               | like CBT and a clinical psychologist, or they can
               | recommend drugs and a psychiatrist. They can do either,
               | for what is the same presentation of problem.
               | 
               | They get seen by a GP, with limited time and tools. They
               | are prescribed SSRIs, and booked in to see "some other
               | health professional" and what emerges is a delay of some
               | significant time, before they get that next stage of
               | engagement.
               | 
               | I was also triaged by my GP, in Australia, and was put
               | into the non-drug path, and I am content. If my health
               | practitioner prefers not to use drugs, and that is a
               | bias, so be it.
               | 
               | I can say that my mother in law was treated in other
               | ways, became addicted to Xanax, and narrowly missed being
               | placed in "deep sleep" therapy which wreaked havoc on
               | many people, although it was "peak treatment" at the
               | time. She was a deeply unhappy woman. I cannot say she
               | would have been better off without drugs, but I do know
               | the process of managing her drug regime was intense.
               | 
               | Deep sleep therapy lasted a long time. It was credible
               | for decades. Psychiatry is as capable as any other
               | science of being led a long way down paths it
               | subsequently walks back on.
               | 
               | ECT, which is much more "confronting" in some ways,
               | remains a useful tool. If you ask most people in the
               | streets, They react with horror.
               | 
               | I place great hopes in ketamine, and in psylocybin.
               | Again, both require a context of use, and are still
               | experimental. What I like about both, is that they appear
               | to being considered as rapid-intervention therapies, not
               | as sustained, long lived treatments. I like that because
               | of the short duration. I guess I don't like the SSRI
               | story precisely because of the long duration, and the
               | consequences on young kids, especially on things like
               | sexual dysfunction. (I'm not a young kid and that isn't
               | an immediate concern for me)
        
               | tptacek wrote:
               | This is for the most part a thread about SSRIs. Xanax is
               | a benzodiazapine. There are no controversies on this
               | thread, or really any ordinary place, about the dangers
               | of benzodiazapines; they're scary drugs.
        
               | ggm wrote:
               | To stick to SSRI's I know one person who reacted badly to
               | a change of meds, predicated on her personal dislike of
               | the effects of the prior, but finding the replacement had
               | extremely strong negative effect. I think had she been
               | absent any support, this could have ended tragically, the
               | effect was so strong and so sudden.
               | 
               | This, coupled with the emerging reports of longterm
               | sexual dysfunction in young women, I think represent
               | pretty severe concerns. Obviously anecdata is not
               | science, but this is what informs my own sense of place
               | here. I am not anti drug in the wider sense. I think
               | drugs of all kinds have been and are and will be
               | beneficial. I am concerned with how SSRIs are being used
               | in practice, with what longterm consequences, and short-
               | term risks.
               | 
               | There's a strong vibe of "butt out, stick to your
               | knowledge" in responses to my posting here. I will take
               | that advice. I'm off-piste, this isn't my area of work.
        
               | klodolph wrote:
               | Agree that the system is a bit fucked, in pretty much
               | every country (as far as I can tell).
               | 
               | Unless you are involuntarily committed, you won't be put
               | on the drug path if you don't want to. Psychiatric
               | medications like SSRIs are generally awful. What I mean
               | when I say "awful" is that the experience of taking them
               | is awful. You may end up with symptoms that are under
               | control, but you may still experience symptoms, or the
               | symptoms can sometimes get worse, and the side effects
               | are often just kind of shitty to deal with. These are
               | generally not habit-forming drugs. These are nasty pills
               | that you'll look at in the morning and dread taking.
               | 
               | Non-compliance rates are already high, when you have
               | patients who _want_ to take the medication. There is no
               | way you 're going to prescribe antidepressants to
               | somebody who says they don't want to take them. It's just
               | a waste of time.
               | 
               | Xanax is different. It's a benzodiazepine. The entire
               | category of benzodiazepines is known to have a high rate
               | of misuse, and Xanax in particular has a high rate of
               | misuse. It's prescribed because it's an extremely
               | effective and fast-acting. Very different from SSRIs.
        
               | mercer wrote:
               | I would add the caveat that low doses of SSRI do seem to
               | be quite effective for issues like compulsiveness and
               | anxiety without much in the way of negative side-effects.
               | 
               | I'm not sure what the scientific support for this is, but
               | at least anecdotally I know 5+ people who take an low-
               | dose SSRIs and claim it works.
        
             | _moof wrote:
             | Psychiatrists are medical doctors. Psychologists are not
             | (and can't prescribe medicine). There is a huge difference.
        
           | aahortwwy wrote:
           | > "Chemical imbalance" isn't actually taught as the root
           | cause of depression.
           | 
           | The article contradicts this.
        
           | asveikau wrote:
           | > It doesn't make sense to make blanket statements about "the
           | drugs" when psychiatric drugs differ widely in this regard.
           | 
           | > I'd be cautious of taking advice from anyone who makes
           | blanket statements about "the drugs". This is bordering on
           | uninformed anti-psychiatry.
           | 
           | Yeah, as someone who has been close to people who need
           | antipsychotics, I sometimes feel the anti-antidepressant
           | crowd extrapolates to _all_ psychiatric drugs and this is
           | very scary. Especially since people with conditions like
           | schizophrenia or bipolar frequently think they don 't need
           | medication.
        
             | fragcula wrote:
             | It's interesting that anyone other than the R&D arm of the
             | pharma industry even cares how it works.
             | 
             | From the medical side what's important is what risk/benefit
             | which is independent.
             | 
             | Antidepressant as a term is really only for convenience
             | which the medications themselves being quite broad in
             | action.
             | 
             | Antipsychotics too are having a bit of a revolution, the
             | first generation seemed to all be about D2 blockade, the
             | second generation acting on 5HT-2a much more than D2.
             | Finally, pimavaserin acting only on seratonin (5HT-2a) and
             | not on dopamine at all [0] now there's SEP-363856 [1] which
             | has action not at D2 or 5HT-2A but TAAR1 and 5HT-1A.
             | 
             | The point is that psychiatrists are not particularly
             | married to any mode of action or mechanism. Only the
             | results.
             | 
             | [0] https://nbn2r.com/search#drug/90
             | 
             | [1] https://en.wikipedia.org/wiki/Ulotaront
        
             | ggm wrote:
             | I am not anti-antidepressant, or drugs in general. Bipolar
             | people get huge benefit from their medications. And their
             | families!
             | 
             | The ones I know also say there are times they miss the
             | emotional highs. It's probably why they (and
             | schizophrenics) go non-compliant.
        
               | asveikau wrote:
               | I think it's different for a lot of people. But one
               | common thing is to get grandiose and think that all
               | problems are with other people. Why would such a person
               | need meds? Clearly there is something wrong with the
               | person who might suggest that.
               | 
               | Then potentially add paranoia on top of that...
               | 
               | Edit: and as the sibling comment said, people can feel
               | pretty shitty on them. I know I've heard and been
               | sympathetic to that for many years, so don't want to
               | sound insensitive by only focusing on anosognosia.
        
               | kayodelycaon wrote:
               | Antipsychotics are nasty medications. Here are the list
               | of problems I've had:
               | 
               | - Sedation (too tired to function)
               | 
               | - Emotional numbness if I need to increase the dose to
               | stop an episode.
               | 
               | - Headache
               | 
               | - Loss of balance.
               | 
               | - Impaired fine motor control.
               | 
               | - My arms and legs don't move properly. I'll command my
               | arm to move, and it only moves halfway. I used to fall a
               | lot before I learned to be very careful walking.
               | 
               | - Inability to orgasm.
               | 
               | These get pretty bad in the first four hours after taking
               | them. During the day, if I get dehydrated or have low
               | blood sugar, I can easily get incapacitated and be unable
               | to drive.
               | 
               | And no, my dosage isn't too high. This is the lowest
               | effective dose I can be on. The alternative is lithium,
               | which can be worse.
        
               | SamoyedFurFluff wrote:
               | I think you might want to do some research as to why
               | schizophrenics might end up non-compliant. Antipsychotics
               | are serious drugs that, historically, have had severe
               | side effects. Additionally, they're rarely a complete
               | solution (people can still have delusions and
               | hallucinations while taking medication). Additionally,
               | like other psychiatric medication, not all antipsychotics
               | will work for people, sometimes they'll stop working,
               | etc.
        
         | makeitdouble wrote:
         | I had the same feedback talking to a few professionals. There
         | is doubt about the exact effect of the prescription and the
         | science behind it, and they regularly have patients that get no
         | clear effect from commonly prescribed treatments.
         | 
         | But they also see other patients showing measurable
         | improvement, and trying different prescriptions until finding
         | one that seem to have an effect is a common practice.
         | 
         | All in all, this is very murky situation, but drug prescription
         | can still be effective and might be the only option for some
         | patient for who other approaches didn't work.
        
           | marincounty wrote:
        
         | Traubenfuchs wrote:
         | 5. the drugs can cause permanent sexual side effects (PSSD)
        
         | jmcgough wrote:
         | > they prescribe both boosters, and inhibitors, to treat the
         | same symptoms
         | 
         | So here's the interesting thing - there's evidence that 5-HT2a
         | receptors are way too dense in people with depression.
         | Antagonists obviously have a blocking effect, but increasing
         | serotonin at the synapse counterintuitively has a similar
         | effect - your body responds to it by paradoxically
         | downregulating 5-HT2a receptors. Two totally opposite
         | approaches with a similar outcome.
        
         | wisty wrote:
         | Maybe just giving the system a kick can be a bit effective
         | (especially in conjunction with a patient trying to change).
        
           | aahortwwy wrote:
           | If you have a broken arm a cast can be helpful during the
           | healing process, but a cast does not heal a broken arm.
        
             | raducu wrote:
             | > but a cast does not heal a broken arm
             | 
             | I don't know why people take such reductionistic stances.
             | 
             | There are dozens of anti-depressants, I think most people
             | get significant improvement after trying a few.
        
               | pessimizer wrote:
               | I don't think the number of different anti-depressants
               | make it inevitable that some work significantly better
               | than others. You can get casts in many different colors.
        
             | kzrdude wrote:
             | It's common to a lot of treatments that we can't heal the
             | body, we can only help it heal itself. Quite amazing in
             | that sense.
        
       | gloosx wrote:
       | So maybe low serotonin levels are caused by depression? My naive
       | understanding is that these amines play a critical role in our
       | emotional response, social interactions and other complex psyche,
       | so as a consequence, depressed person suffers decline in these
       | functions, as well as a whole higher nervous system suffers
       | regression. I always had a feeling that SSRIs are treating
       | consequence, not the cause. Maybe I'm too naive and my
       | understanding is very poor, I just architect systems in the end,
       | so I'm looking at this problem like at a bug in the very root of
       | an unimaginably complex system, while treating it by boosting one
       | or another amine is looking like the most ugly hotfix.
        
         | neuroma wrote:
         | As we're dealing in analogies...
         | 
         | Better think the serotonin/ monoamine hypothesis of depression
         | is akin to saying a server load balancing failure is because of
         | "electricity imbalance". Whilst electrons are undeniably
         | involved, the explanation is not useful, and distracts from
         | better truths.
         | 
         | We have such a scarcity of safe and effective tools to probe
         | and influence the human brain. Herein lies the hope that the
         | diseases we invent might be treated neatly by the tools we
         | posses. Yet, given the origin of disease and the tools are
         | sparsely interlinked, it is too often just a fantasy.
         | 
         | Yet to "do nothing" is usually not acceptable and so we
         | persist, and iteration or invention become the next hope.
        
           | malf wrote:
           | "electricity imbalance" may be a myth, but a short
           | electricity "fast" (HYTTIOAOA) is still a useful fix for many
           | problems.
        
         | taurath wrote:
         | That's my understanding and feeling as well. Psychiatric
         | medication imo should be used to help stabilize for
         | psychological work, not create a new chemical baseline.
        
       | [deleted]
        
       | current_thing wrote:
       | https://m.youtube.com/watch?v=tFgF1JPNR5E&t=9m35s
       | 
       | Tom Cruise was right then.
        
         | sigg3 wrote:
         | Tom Cruise is a leading member in the fascist cult Church of
         | Scientology, who is on record saying they can bring back people
         | from the dead and levitate.
        
           | bowsamic wrote:
           | And? People also listen to Buddhists about depression, and
           | Buddhists believe that enlightened people can fly!
           | 
           | EDIT: I'm rate limited so I can't reply to the child
           | comments:
           | 
           | I think a majority of Buddhists believe that Buddhas and
           | bodhisattvas have special powers. It is in a majority of the
           | traditional scriptures, from both Mahayana and before. I
           | don't think the authoritarian nature of scientology changes
           | the situation. Scientologists were being mocked for believing
           | in such things, but that is not far from the beliefs of most
           | Buddhists which people will happily listen to.
           | 
           | I mean, you will likely even listen to His Holiness the Dalai
           | Lama, who is literally a prophesied reincarnation of the
           | bodhisattva Avalokiteshvara (Guanyin in Chinese, Kannon in
           | Japanese)
           | 
           | My point isn't that people can be right about some things and
           | wrong about others, it's that people mock their disliked
           | religious figures on one basis, but their mocking also
           | applies just as much to their favourite religious figures,
           | however they don't realise it because they are usually
           | ignorant to many aspects of it. Everyone loves Buddhism, but
           | go and criticise other religions for reasons that apply just
           | as much to Buddhism, they are just ignorant that it also
           | applies to Buddhism.
           | 
           | I am a devout Buddhist, and believe in these traditional
           | things, such as Buddhas flying or having their own Buddha
           | lands or faith in my rebirth in a western Pure Land. I
           | emphasise it because you probably don't know of these things
        
             | telchior wrote:
             | "Buddhists" represents many sects, and many more
             | individuals who aren't beholden to anyone. The majority of
             | these assuredly don't believe anyone can fly, enlightened
             | or not.
             | 
             | Scientology is a rigidly hierarchical, authoritarian cult
             | that speaks with a single voice: that of a handful of
             | leaders.
             | 
             | There is a slight difference between these two things.
        
             | ok_dad wrote:
             | What do Buddhists have to do with Tom Cruise? Is he a
             | leading member of a Buddhist organization?
        
               | neonate wrote:
               | I assume bowsamic's point is that people can be wrong
               | about some things and right about others.
        
               | ok_dad wrote:
               | It was whataboutism, and it successfully derailed the
               | conversation, so I guess it worked.
        
               | bowsamic wrote:
               | It isn't whataboutism. I'm simply pointing out that the
               | same argument people use to disparage Tom Cruise also
               | applies to religious figures that they respect far more.
               | I'm pointing out ignorance about other religions, it
               | isn't whataboutism at all.
        
               | ok_dad wrote:
               | In Scientology's case, there is a bit more to it than
               | just believing some monks can fly.
        
         | dang wrote:
         | We detached this subthread from
         | https://news.ycombinator.com/item?id=32160909.
        
       | imadierich wrote:
        
       | cbxyp wrote:
       | SSRI's are without a doubt the leading cause of divorce and mass
       | shootings in America. The quacks in the medical profession
       | handing them out like candy to people whom it is clearly
       | contraindicated in, without any followup study and usually
       | without any competent analysis of what the drugs are doing to
       | these peoples behavior and brains. Getting my girlfriend off of
       | SSRI's completely changed her life, as she was indicated bi-
       | polar, and yet over 10 mental crisis hospitalizations with
       | specialist psychiatry teams failed to notice the direct
       | contraindication and continued recommending use of SSRIs. The
       | kind of mental breakdowns she was having as a direct result of
       | SSRI use is the type of behavior that in a male could lead to a
       | mass shooting or other particularly crazy behavior.
       | Uncontrollable flights of emotions and repeating panicked
       | behavior.
       | 
       | After seeing her be "treated" by numerous psychiatrists who
       | failed to take note or recommend cessation despite SSRI usage
       | being _clearly_ contraindicated on her pre-existing diagnosis,
       | the last crisis we simply took her to another hospital, they
       | concurred on cessation of SSRIs and all of these problems ceased.
       | Of course, it 's not possible to sue the previous doctors or
       | hospital due to the laws that protect the industry.
        
         | chalst wrote:
         | > without a doubt
         | 
         | Not a mark of wisdom to use these words about such topics.
         | 
         | I agree that SSRIs and bipolar are a tricky mix, but they work
         | for some patients.
        
           | cbxyp wrote:
           | Divorce: https://pubmed.ncbi.nlm.nih.gov/23931947/ Mass
           | shootings / violence:
           | https://www.psychreg.org/antidepressants-ssri-mass-
           | shootings...
           | 
           | While they may provide benefit to some patients, the sheer
           | volume of prescriptions and the quite clearly linked effect
           | leads me to stand by my original statement - without a doubt,
           | they are a leading cause of both.
        
             | chalst wrote:
             | The existence of studies attesting to a link does not
             | demonstrate causation beyond reasonable doubt.
        
       | jinder wrote:
       | SSRIs appear to work through the vagus nerve in a similar way to
       | psychobiotics. Their direct effects on neurotransmitters are
       | probably an unwanted side-effect:
       | 
       | Oral selective serotonin reuptake inhibitors activate vagus nerve
       | dependent gut-brain signalling (2019):
       | https://www.nature.com/articles/s41598-019-50807-8
       | 
       | Identification of SSRI-evoked antidepressant sensory signals by
       | decoding vagus nerve activity (2021):
       | https://www.nature.com/articles/s41598-021-00615-w
        
         | jinder wrote:
         | To add to my comment, this explains why SSRIs take some time to
         | work - it's the signalling through the vagus nerve that takes
         | time to impact the brain. Other compounds such as curcumin and
         | famotidine (H2 antihsitamine) have also been found to work via
         | this mechanism. For many many years scientists had dismissed
         | curcumin as having no effect because it's not bioavailable -
         | recent research has shown that it doesn't need to be if it
         | directly activates your nervous system! There's a lot more
         | research that needs to be done here, and I think promising
         | therapeutics for impacting brain function are coming our way as
         | researchers learn more.
         | 
         | If you consider the brain a state machine, inputs from the
         | nerves - through gut-brain axis, through your eyes and ears
         | (socialising, environmental cues, sounds of safety vs sounds of
         | threat), through your skin (touch) etc all impact the state.
         | This state can range from safety to fight-or-flight (anxiety)
         | to shutdown (depression). This is hugely simplified (for
         | example neuroinflammation, endotoxins/LPS etc can impact this
         | also) but I've found it very useful for regulating my own state
         | and understanding why I feel happy, agitated, low etc.
        
         | konfusinomicon wrote:
         | recently procured an acupressure spiky foot ball that was
         | originally designed to combat depression by stimulating the
         | vagus through the foot. I don't consider myself depressed by
         | any means, but after a few minutes of rolling my feet
         | aggressively over the ball and targeting a few key areas, I
         | generally feel much better and can actually sense that my body
         | is less stressed. everyone should have one or 2 of them
        
           | 72deluxe wrote:
           | This is very interesting - is that just a general acupressure
           | spikey ball? I am looking for one on Amazon, if you had the
           | link?
           | 
           | Also, reading up on the vagus how is the vagus stimulated via
           | the foot? Reading on wikipedia on the vagus nerve I cannot
           | see how it is connected to the foot in any way?
           | 
           | Thanks in advance
        
             | konfusinomicon wrote:
             | apologies, it wasn't vagus, it was the solar plexus, a few
             | inches back from the 2nd biggest toe. got mine from
             | gokanjo.
        
             | WalterSear wrote:
             | It's connected to the vagus nerve via the leader of the
             | 1950's Chinese communist party:
             | 
             | https://slate.com/technology/2013/10/traditional-chinese-
             | med...
        
       | tested23 wrote:
       | There are probably a million different causes for depression and
       | im convinced for all but the most extreme cases that usage of
       | anti depressants is a mistake.
       | 
       | I think viewing depression as a disease instead of a symptom is a
       | mistake. So many people eat food completely devoid of nutrition,
       | stay indoors all day, have erratic sleep schedules, drink absurd
       | amounts of alcohol and smoke weed all day. Why are we giving
       | these people antidepressants when what they need is to go outside
       | and walk and to take a multivitamin?
        
         | quacked wrote:
         | Completely agree with you, although I think that "going outside
         | and taking a multivitamin" is an inadequate substitute for
         | "live inside a prosperous, functional human-shaped society".
        
           | gillytech wrote:
           | It's not society. It actually starts with the individual. In
           | order to have nay kind of decent society, each individual
           | needs to recognize that they are responsible for themselves
           | and their own society. Going outside, exercising and
           | consuming nourishing foods are the literal starting place.
           | Then seek to find things you like doing and become competent
           | in them. Find a good wife or husband. Don't cheat on them.
           | Don't take alcohol to excess, etc. etc.
           | 
           | The point is, you cant start from the outside and work your
           | way down the the individual. It starts with the person.
        
             | DontchaKnowit wrote:
             | While this is true in terms of finding a solution to
             | depression, I do think that the societal norms of our
             | society are extremely conducive to these sort of depressive
             | behaviors. E.g. many societies are setup to make these
             | kinds of behaviors (self isolation, dopamine seeking
             | hedonic treadmill type behavior, etc) very difficult to
             | engage in without being chastised
        
               | gillytech wrote:
               | I see your point, and my argument supports it. Who
               | creates "societal norms" other than the individuals that
               | make up society? It starts with individual action to
               | reverse the dwindling spiral.
        
               | DontchaKnowit wrote:
               | Sure. It is certainly a "collective action" type problem.
        
             | quacked wrote:
             | I completely disagree with that. If you are a westerner
             | with a 50th percentile mind and follow every rule set up
             | for you, you end up on a console for 8-10 hours per day,
             | struggling with bills and health insurance and watching the
             | land and culture around you be slowly eroded into a
             | formless mass of concrete and advertisements.
             | 
             | "Depression" is a natural response to living an alienating
             | modern lifestyle. The people who can appropriately "deal"
             | with it (like myself) all have something extra going for
             | then, like deep family structures or unusual minds.
        
       | ChildOfChaos wrote:
       | The book lost connections is a really good read on this.
       | 
       | It points out the problems in modern society and our lives that
       | lead to depression rather than it just being something that can
       | be solved with a pill.
       | 
       | Things like our lack of connection to meaningful work, our lack
       | of connection to each other and our lack of connection to nature
       | all play a big part.
        
         | falafelite wrote:
         | I found the author to have cherry-picked and poorly-cited
         | information earlier on in the book when talking about
         | antidepressants, and then a complete lack of rigor when
         | discussing the various lost connections. I think he has a
         | point, but I just didn't find it very well done, and as another
         | comment here has quoted: > Other clinicians say, however, that
         | the notion of depression being because of a simple chemical
         | imbalance is outmoded anyway, and that antidepressants remain a
         | useful option for patients alongside other approaches including
         | talking therapies.
         | 
         | It is also notable that the author has had plagiarism issues
         | and other questionable behaviors in the past:
         | https://en.wikipedia.org/wiki/Johann_Hari#Plagiarism_and_fab...
        
         | 127 wrote:
         | There's also the driving our novelty seeking brains into
         | overdrive with all kinds of artificial stimulants, including
         | this very forum.
        
         | n0tth3dro1ds wrote:
         | Sounds like Kaczynski's "power process" in Industrial Society
        
         | richardatlarge wrote:
         | I recommend "The Cult of Pharmacology," which long ago
         | characterized this serotonin theory as bio-babble reductionism
        
       | smolder wrote:
       | I'm going to go out on a limb and guess the prominence of
       | depression is _largely_ caused by a broken interface with the
       | world at large. The traps created by modern society wherein you
       | struggle for other people 's benefit are better designed than
       | ever before. What our social machine procedurally treats as
       | progress is advances in subjugation. Depression may often be an
       | artifact of "efficiency" with respect to extracting value from
       | the population at large. We might need to dial back the
       | exploitation of the currently-exploitable class to have a
       | sustainable society, assuming pills don't work. In different
       | terms, maybe we have too many rich people (exploiters) in a
       | situation where it's clearly very foolish to keep growing in
       | number (and productivity) to support them. Maybe we just need to
       | rebalance our economy to make it work better for those currently
       | exploited and endemically depressed people.
        
         | bawolff wrote:
         | > In different terms, maybe we have too many rich people
         | (exploiters) in a situation where it's clearly very foolish to
         | keep growing in number (and productivity) to support them.
         | Maybe we just need to rebalance our economy to make it work
         | better for those currently exploited and endemically depressed
         | people.
         | 
         | Don't all those rich people also get depression? I think that
         | rules out a marxist reading here.
         | 
         | If you're going to go this general direction, i'd say a better
         | way would be, we now live in a system where work is never done,
         | stress is pretty constant, and labour is less physical but more
         | mental in the modern world. Perhaps our mind is just not made
         | for continous mental labour. Being a farmer in pre modern times
         | sucked, but at least you could turn your brain off more often.
        
           | imtringued wrote:
           | People lament their functional redundancy in society. Markus
           | Persson Notch got depression after he became a billionaire.
           | The workers lament their redundancy because they can be
           | replaced and abandoned all the time.
           | 
           | People want to be needed, instead we have become isolated
           | individuals that need no one in particular.
        
           | hikingsimulator wrote:
           | Marx clearly stated that alienation was a phenomenon that
           | affected all classes. Marxism explains alienation just
           | intervenes in a different manner.
           | 
           | Depression then also happens among rich people. But the
           | source, and expression of it might differ. An anecdotal
           | saying explains that wealth is often a barrier to create true
           | friendships because it insulates you from society and creates
           | antisocial thought processes: the "thinking people just want
           | to be your friend because you're rich" rhetoric.
        
           | smolder wrote:
           | Rich people aren't automatically immune to exploitation. It's
           | more a finely tuned web of pressures than a strict hierarchy.
           | I'm also aware of differences in genetics and diet and other
           | behavior that predispose people to depression.
           | 
           | I'm not rooting for Marxism exactly. I think it is an extreme
           | overcorrection, but that some correction has been and is
           | still warranted at times, given regulatory capture and other
           | abuses that come from concentration of power. Anti-trust
           | action and semi-effective democracy/representation are
           | needed.
           | 
           | I think we are in a society with solutions to almost every
           | problem except for those that require cooperation on the
           | scale we exist at, which is unprecedented.
           | 
           | I sympathise with the idea of mindless hard labor being more
           | fulfilling. Working food service in the backroom as a
           | teenager worked my body but left me less stressed mentally
           | than anything I've done post-graduation.
        
         | tptacek wrote:
         | You're right: you've gone way out on a limb.
        
           | emodendroket wrote:
           | I've heard plenty of people involved in mental health care
           | themselves lament the fact that they're often just trying to
           | happy-talk people who genuinely have harrowing lives. I don't
           | think the notion is absurd.
        
             | tptacek wrote:
             | All sorts of non-absurd-seeming notions turn out to be
             | wrong, which is why people train for many years to conduct
             | medical research.
        
               | emodendroket wrote:
               | How would you "medically disprove" the notion that some
               | people are unhappy because the circumstances of their
               | lives are bad rather than biological defects?
        
               | nl wrote:
               | Unhappy is dramatically, completely different to
               | depression. I've been both and they don't even feel that
               | similar.
        
               | dr_dshiv wrote:
               | Sadness or distress vs not feeling anything and not
               | having motivation?
        
               | nl wrote:
               | Yes, this is roughly in the right area.
        
               | dr_dshiv wrote:
               | I wonder how a week of low dose amphetamine usage, like
               | adderall, might help disrupt no-motivation mood loops. A
               | friend of mine (cycling through many antidepressants)
               | seems like he would respond well to this. As in, he would
               | feel better and be able to "shift gears." Not to get more
               | work done, but say, enjoy going to an art museum. And
               | feel what it is like to be enthusiastic again.
        
               | emodendroket wrote:
               | If we change the word "unhappy" to "despairing" does it
               | make sense?
        
               | nl wrote:
               | I don't know - it's your argument.
               | 
               | If it helps, unhappiness/despair seem like different
               | degrees of the same feeling. Depression is a different
               | feeling.
               | 
               | The closest analogy I can think of is that "amused" and
               | "satisfied" are both positive feelings, but they are
               | different and you can't treat the cause the same even if
               | some of the symptoms are similar.
        
               | emodendroket wrote:
               | "Exogenous depression" is supposed to be experienced by
               | about a fifth of people at one point or another. What if
               | many persistent cases of depression were actually
               | exogenous? That might be more interesting than parsing
               | the difference between despair, hopelessness, anhedonia,
               | and depression.
        
               | NavinF wrote:
               | No
        
               | emodendroket wrote:
               | Thanks for your contribution to the discussion.
        
               | tptacek wrote:
               | Nobody needs to disprove the notion that some people are
               | happy for reasons having nothing to do with clinical
               | depression.
        
               | emodendroket wrote:
               | OK. And the notion that psychiatry has been used to
               | simply stamp anyone agitating for political change as
               | insane is also attested (see
               | https://en.wikipedia.org/wiki/The_Protest_Psychosis for
               | instance). So what's your objection to this line of
               | inquiry?
        
               | tptacek wrote:
               | I don't know what you're trying to argue here, but it
               | doesn't seem to have anything to do with the claim at the
               | root of the thread, and I apologize but I'm not
               | interested in the tangent.
        
             | JamesBarney wrote:
             | The idea that a terrible life can cause depression is not
             | the limb he's going out on. It's the idea that somehow
             | depression is caused by being way more exploited than our
             | ancestors in the 1700's who were working on someone else's
             | farms and factories as children is the limb he's going out
             | on.
        
               | smolder wrote:
               | Fair criticism as usual and maybe I should have been more
               | specific, but I didn't say anything about the 1700s or
               | prior specifically. If we talk about trends in the
               | lifespan of people alive today (which represents a huge
               | number of people) the picture is much different.
        
               | Thorrez wrote:
               | My grandma (alive today) grew up with no indoor plumbing
               | in the United States. They had to use an outhouse.
               | 
               | > In 1940 nearly half of houses lacked hot piped water, a
               | bathtub or shower, or a flush toilet. Over a third of
               | houses didn't have a flush toilet.
               | 
               | https://www.aceee.org/files/proceedings/2004/data/papers/
               | SS0...
        
               | emodendroket wrote:
               | OK, well, that's an easy rhetorical maneuver but one that
               | can be met with equally facile ripostes, such as "how do
               | you determine that people weren't just as if not more
               | depressed in the 18th Century when the concept was less
               | familiar?" or "perhaps having the gulf between themselves
               | and the wealthy rubbed in their faces every day is what
               | causes the distress, since there can be little sense of
               | exploitation if one is surrounded only by those in
               | similar straits."
        
               | Thorrez wrote:
               | Didn't people in the olden days also see the castles and
               | mansions of the rich on a daily basis?
        
               | emodendroket wrote:
               | Daily I very much doubt because it's not like most people
               | were commuting to work. Would you sometimes see them,
               | sure, but people also had a belief system that would have
               | done more to justify the social order, and it would
               | probably be limited to provincial elites for most.
        
               | missedthecue wrote:
               | You don't need to go back to the 1700s to find
               | comparatively low levels of depression. The 1980s will
               | do.
        
               | UK-Al05 wrote:
               | Is it exploitation that's the problem?
               | 
               | Or social isolation? People are very isolated these days.
               | People can have good jobs, have lots of shallow
               | acquittances but no true friends.
        
         | dogcomplex wrote:
         | Gonna attempt to short circuit the "you think WE have it bad?
         | Whatabout 1700s?" argument by adding that the "broken
         | interface" theory may be much more about the patient's
         | _perception_ and _confidence_ of the trap we 're in than the
         | actual truth of relative conditions. There also might now be a
         | greater philosophical understanding of the global picture than
         | the average person back in the day. Back then we didn't have an
         | internet to give us rigorous detail on both the widespread
         | extent the human race is trapped in a broken system and the
         | futility of the common man's attempts to change it. Even if
         | this wasn't true (I'm hard pressed to find a more optimistic
         | take, though I'm always searching and fighting for it -
         | technology is the best hope imo), it is an easy perception to
         | fall into, especially for anyone already a few steps into
         | depression. It's a reasonable bet that even if people in the
         | past were just as likely to get beaten down and depressed about
         | their own lives, they still might have been able to look at the
         | world around them and the future of humanity and see optimism
         | and hope that the next day might be better/luckier. The world
         | was also much more malleable at the local level - both
         | politically and individually (i.e. go outside and chop a tree
         | down) and less of a complex leviathan of laws and exploitations
         | which immediately instills a feeling of being trapped in the
         | jaws of something that you can't even explain or understand.
         | 
         | Alternatively - or just, adjacently - with the internet (and
         | big business, and widespread university education) we are
         | culture-shocking vastly more people into a medium that can
         | barely be understood from a detached intellectual and
         | philosophical perspective, and is almost impossible to fathom
         | from historical, traditional, ancestral or biological ways of
         | understanding (the way humans operated for vast majority of our
         | existence). We have little history to compare this new way of
         | life to, and it's unsurprising if it's doomed to breed mental
         | disease by its very nature. We have awakened far more people to
         | an absurd reality, and "what is meaning?" is no longer just a
         | question for a tiny group of overintellectual philosophers.
         | Some of those philosophers say that one must walk through the
         | valley of the shadow of death before we can find that answer
         | for ourselves - but even they're gonna admit that a whole lot
         | of people are gonna get stuck in that valley for a while if you
         | just throw the masses in like we have. Hopefully that's just a
         | temporary growing pain of our society as we gather our strength
         | and do better but - time will tell!
         | 
         | (P.S. rich people are just as trapped in this malaise of
         | meaninglessness. They have more agency, sure, but they're also
         | still part of the systemic trap and unlikely to have much
         | better answer on how to change anything than the common man.
         | Only so long even a rich person can hide in hedonism before the
         | depression catches up - or they just embrace the cold reality
         | and adopt the "I got mine" attitude which said system is
         | naturally inclined to. Depression may very well be due to our
         | moralistic social being nature chafing with a cruel capitalist
         | system which has won by almost every measure possible)
        
           | smolder wrote:
           | Yes, honestly I regret making the jab at "rich people". It's
           | oversimplifying things.
           | 
           | I appreciate your take on this.
        
             | zackmorris wrote:
             | Don't feel too bad about it, you hit the nail on the head.
             | 
             | It might be helpful though to define the term "rich".
             | 
             | A rich person usually isn't your manager, or their boss, or
             | even the owner of the business, because the people
             | supervising you may have never had a raise in life either,
             | and the owner might be in debt.
             | 
             | A rich person is someone who dismisses their dependence on
             | others. They will act impeccably in all situations and
             | often appear to have an untarnished reputation. A rich
             | person will deny help to someone in need, and then justify
             | their lack of empathy with something along the lines of
             | tough love. A rich person will demand that others work and
             | portray an image that they themselves work, while secretly
             | delegating all work to others. A rich person will wear a
             | suit, a lapel pin, all manner of regalia, to preserve their
             | image at all cost. A rich person has an untethered ego that
             | will go to any length to maintain control. A rich person
             | will decide for others. A rich person will never question
             | their own beliefs. A rich person achieves affluence by
             | denying it to others.
             | 
             | Unfortunately the rich are in charge of all facets of our
             | lives in the US and pretty much everywhere else. Their
             | undying devotion to wealth inequality and the status quo is
             | specifically the primary cause of suffering for the rest of
             | us.
        
         | raptorraver wrote:
         | I tend to think that our disconnection from the nature causes
         | depression to humans. We have come so far from our natural
         | living conditions that we fall ill to depression and other
         | diseases. Another aspect is the lack of physical work that is
         | very unnatural for us. We sit in cubicles (or at home office
         | nowadays), use our brains and fingers to do work and at best
         | hit the gym few times a week. After which we eat our stomach
         | full and entertain us with things that were invented during
         | last generation. Life certainly is safer and better for us, but
         | it's making us unhappy. We live like medieval royals and like
         | them we suffer mental illnesses
         | (https://en.wikipedia.org/wiki/List_of_mentally_ill_monarchs).
        
         | [deleted]
        
         | oq_computer wrote:
         | 'The Weariness of the Self' from Alain Ehrenberg gives a really
         | good account about the history of the depression more or less
         | along these lines.
        
         | taurath wrote:
         | Imagine a kid growing up in the US today, they are functionally
         | under house arrest as neighborhoods are built for cars and not
         | people. Everyone is isolated to their family unit almost
         | entirely and all activity gated on parents time and willigness
         | (or control).
        
         | JamesBarney wrote:
         | You must be reading very different history books than the ones
         | I've read.
         | 
         | The idea that we're somehow way more exploited than the people
         | who came before us does not seem compatible with any history
         | book I've ever read.
        
           | smolder wrote:
           | It depends on the timespan and comparative frame you are
           | thinking about. If we limit ourselves to post-WW2 MAD world,
           | there are much different overall trends in quality of life
           | than starting in the middle ages or from colonial times,
           | where many people did not enjoy the rights or luxuries modern
           | people would, not in small part because they couldn't,
           | technologically speaking. It's easy to compare modern poverty
           | to peasantry and say we have it good now, but it doesn't
           | address modern problems in a meaningful way.
        
             | tomnipotent wrote:
             | > It depends on the timespan and comparative frame you are
             | thinking about
             | 
             | There are few dimensions where pre-industrial life is
             | better before than after. The quality of life for the
             | average human is many standard deviations above what it was
             | just a few centuries prior. It wasn't that long ago cholera
             | was a death sentence.
        
           | scsilver wrote:
           | Have you ever wondered why the user is the product in so many
           | internet companies?
        
           | hoseja wrote:
           | Turns out it's more efficient to keep the cattle somewhat
           | happy. Doesn't change a thing when it comes time to get
           | steak.
        
           | eurasiantiger wrote:
           | Before, the body was in chains, but the mind was free.
           | 
           | Now, the mind is in chains.
        
             | becquerel wrote:
             | What evidence do you have for this? Do you think chattel
             | slaves of the USA weren't broken in mind - indoctrinated
             | into Christianity, stripped of their original languages,
             | culture and names? That was not some novel evil created by
             | Southerners - it's the tried-and-true method for enslaving
             | populations throughout history.
             | 
             | But I'm sure the existence of TikTok is an existential
             | threat.
        
               | eurasiantiger wrote:
               | How successfully?
        
             | white_dragon88 wrote:
             | Lol so dramatic.
        
         | randomopining wrote:
         | Equal and opposite reaction. Right now may literally be the
         | best time to be alive in the world history for those who have
         | direction, purpose, inner strength. Endless possibilities and
         | safety nets.
        
       | jwmoz wrote:
       | Right, so who's correct?
        
       | lettergram wrote:
       | One of the most interesting things I heard recently that really
       | hit me like a bolt of lightning...
       | 
       | Depression is a disease of despair, and all these treatments are
       | really just treating the symptoms.
       | 
       | In other words, people experience despair because of some
       | underlying situation - examples: death of child, lonely, broken
       | home. "Normal" things, and we try to treat it with
       | pharmaceuticals. It would be like treating depression with
       | cocaine or marijuana (they actually did and still do this btw) -
       | might make you feel good temporarily; but it'll never stop the
       | despair.
       | 
       | The question is really how to address the despair. People often
       | visit a therapist; I can see that helping some. But to many, they
       | can't seem to find the cause.
       | 
       | It reminds me of the post the other day about how people live
       | over 100 [1]. It's all about community:
       | 
       | > Belong. All but 5 of the 263 centenarians interviewed belonged
       | to some faith-based community. Denomination does not seem to
       | matter. Research shows that attending faith-based services 4
       | times per month will add 4 to 14 years of life expectancy.
       | 
       | > Loved ones first. Successful centenarians in the Blue Zones put
       | their families first. This means keeping aging parents and
       | grandparents nearby or in the home (it lowers disease and
       | mortality rates of children in the home too.). They commit to a
       | life partner (which can add up to 3 years of life expectancy) and
       | invest in their children with time and love. (They'll be more
       | likely to care for aging parents when the time comes.)
       | 
       | > Right tribe. The world's longest lived people chose--or were
       | born into--social circles that supported healthy behaviors,
       | Okinawans created moais--groups of 5 friends that committed to
       | each other for life. Research from the Framingham Studies shows
       | that smoking, obesity, happiness, and even loneliness are
       | contagious. So the social networks of long-lived people have
       | favorably shaped their health behaviors.
       | 
       | Yes some people have real hormone or other biological issues. But
       | 99% of people likely need to address the root cause. I'd put
       | money depression is on the rise as our communities are collapsing
       | due to the industrial / technological nature of our world.
       | 
       | [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125071/
        
         | klodolph wrote:
         | Bolts of lightning can be factually wrong, it sounds.
        
           | lettergram wrote:
           | No doubt, but this article is about how the SSRIs don't seem
           | to be effective.
           | 
           | To be clear a disorder (ie depression disorder) can be caused
           | by a variety of factors, including (but not limited to):
           | genetics, environment, trauma, illness, etc.
           | 
           | Given that's the case, some drugs may help ease symptoms
           | (depression being the symptom), but finding and correcting
           | the root cause (if possible) is important.
           | 
           | Unfortunately, the medical industry as a whole has very
           | little reason to try and "cure" these diseases / disorders.
           | Why would a therapist? Why would a pharmaceutical company?
           | Recurring revenue to ease symptoms is perfect.
           | 
           | Which imo is why this is often not discussed. The vast
           | majority of the research money is poured into drug research
           | or clinical research around therapies. Often this overlooks
           | other avenues -- one which I mentioned.
        
             | amanaplanacanal wrote:
             | > this article is about how the SSRIs don't seem to be
             | effective.
             | 
             | I believe they can be effective in reducing depression, it
             | just has nothing to do with serotonin.
        
             | klodolph wrote:
             | > No doubt, but this article is about how the SSRIs don't
             | seem to be effective.
             | 
             | Where does the article say that?
             | 
             | > Given that's the case, some drugs may help ease symptoms
             | (depression being the symptom), but finding and correcting
             | the root cause (if possible) is important.
             | 
             | It's not for lack of trying.
             | 
             | > Unfortunately, the medical industry as a whole has very
             | little reason to try and "cure" these diseases / disorders.
             | Why would a therapist? Why would a pharmaceutical company?
             | Recurring revenue to ease symptoms is perfect.
             | 
             | That explanation doesn't have any legs.
             | 
             | By this theory, dentists have no incentives for
             | prophylaxis, but in practice, that's a large part of what
             | dentists do and it's very effective. By this theory, the
             | medical industry wouldn't choose to eradicate any
             | infections diseases, since it can make money from
             | treatment. It turns out we can and do eradicate infectious
             | diseases, but it is difficult, expensive, and time-
             | consuming. We've only successfully eradicated two
             | infectious diseases and only one of those affects humans in
             | the first place.
             | 
             | If you look at other infectious diseases, there are tons of
             | diseases which can be outright cured and tons which can't.
             | This isn't for lack of trying, it's just that these
             | diseases are different. You can kill bacteria with
             | antibiotics, but if you get HIV, the best we can do is
             | antiretroviral therapy.
             | 
             | Treatment of symptoms with pharmaceuticals is often a
             | rational, good decision. There are simply too many diseases
             | for which we don't have any known cure. Depression is one
             | of them. The disease is too complicated, or the cure is too
             | difficult, or our understanding of depression is too
             | primitive, or some combination of all three. So we have
             | stuff like SSRIs, which are known to work for some people.
        
               | lettergram wrote:
               | > The disease is too complicated, or the cure is too
               | difficult, or our understanding of depression is too
               | primitive, or some combination of all three.
               | 
               | I don't think we disagree in almost any of this.
               | 
               | I'm simply pointing out depression may be caused by
               | environmental factors, one which can be treated. It could
               | be why they found "nothing convincing" in the study.
               | 
               | I have yet to meet a depressed person or almost any
               | person who couldn't use more community. I suspect most
               | peoples depression is a rational / emotional response to
               | lack of basic needs of some kind. Whether that's
               | community, sleep, job, food, etc
               | 
               | That's not to say all people have environmental factors
               | or that drugs can't help people cope. I'm merely sharing
               | what struck me and for some reason hadn't clicked with me
               | prior, even seeing people get out of depression.
               | 
               | The people I know who overcame depression all did the
               | following: worked out, improved sleep patterns, joined
               | some activities. One could argue correlation (ie as
               | depression reduced, they became more active). But it
               | didn't seem that way looking in. Anyway, just an
               | observation and contemplation really.
        
               | klodolph wrote:
               | > I have yet to meet a depressed person or almost any
               | person who couldn't use more community.
               | 
               | Depression is known to _cause_ this. Yes, it's not that
               | simple. But this reasoning is extremely dubious.
               | 
               | > The people I know who overcame depression all did the
               | following: worked out, improved sleep patterns, joined
               | some activities.
               | 
               | All the people I know who graduated high school got
               | married and had children. Maybe we should encourage
               | people to get married and have children to increase the
               | graduation rate!
               | 
               | Sarcasm aside, this reasoning is just beyond dubious. Do
               | you know what the symptoms of depression are? Are you
               | familiar with the very basics of what depression is? All
               | of the things that you described that people overcame are
               | actual symptoms of depression.
               | 
               | Or maybe to abuse another analogy--everyone I know who
               | got over chicken pox stopped getting those pustules. That
               | doesn't make "stop getting pustules" actionable advice!
        
           | bwood wrote:
           | Sure, but it would be more constructive to explain why it's
           | wrong. GP's comment has some interesting ideas and it would
           | be better to directly refute them than just claiming they're
           | "factually wrong".
        
             | klodolph wrote:
             | Sorry, thought it would be obvious.
             | 
             | > Depression is a disease of despair,
             | 
             | > The question is really how to address the despair.
             | 
             | It's known that people have genetic predispositions to
             | depression. People experience depression due to many
             | causes. Not all causes are known and we don't have very
             | good understanding of the mechanisms, but it's just not
             | damn likely that we can treat this as a purely
             | psychological / environmental issue.
        
       | standardly wrote:
       | " _I_ think depression is _really_ caused by X, and anti-
       | depressants are really just a placebo "
       | 
       | It's tough to quantify the efficacy of AD's, especially given the
       | differences in individual neurochemistry, but claiming they don't
       | work at all, or that depression isn't even real, is plain
       | ignorant.
       | 
       | Everyone should be forced to watch Dr. Sapolsky's lecture before
       | commenting on depression:
       | https://www.youtube.com/watch?v=NOAgplgTxfc
        
       | VLM wrote:
       | There's two separate medical systems, one focused on making money
       | and boosting financials where science does not matter, and the
       | other focused on medical science where at least theoretically the
       | financials do no not matter.
       | 
       | Its up to the end user to figure out which system they're
       | interfacing with and act accordingly. Hint, antidepressants make
       | a lot of money for the correct people... People who make
       | treatment decisions based on financials and kickbacks are not
       | going to care about all this "science" and "logic" and
       | "statistics" stuff where their wallet is concerned.
        
         | jugg1es wrote:
         | I understand where your cynicism comes from but I think it
         | might be overblown in this case. These drugs do help people and
         | psychiatrists want to help. The fact is that we just don't know
         | that much about how higher cognition works. I have a
         | neurobiology degree and was very surprised how little we
         | actually know.
         | 
         | We don't know how to really measure things like depression, so
         | we rely on animal models and medieval tests such as "Lets throw
         | this mouse into a bucket and see how long it takes for it to
         | give up treading water".
         | 
         | When we are able to take 'in situ' measures in a live person
         | without risking their life, we may start to make progress on
         | better treatments.
        
         | SkyPuncher wrote:
         | > People who make treatment decisions based on financials and
         | kickbacks are not going to care about all this "science" and
         | "logic" and "statistics" stuff where their wallet is concerned.
         | 
         | Can you elaborate on who these people are? You're casting a
         | wide net here.
         | 
         | My partner works in mental health. The reality I've observed is
         | mental health is incredibly challenging. Much of it is highly
         | situational and requires hours and hours of extremely time
         | consuming, labor intensive therapy to even begin creating a
         | meaningful treatment plan. If mental health had unlimited time,
         | many providers would love to be able to provide this level of
         | care.
         | 
         | In practice, medications are a highly cost-effective means of
         | improving people's mental health. They can increase people's
         | baseline significantly with therapy (time and cost) focusing on
         | rounding out the rough parts. Many patients are not interested
         | in the therapy component if they can get "80%" better with some
         | medication.
         | 
         | IMO, this is why we're seeing such a boom in "pill mill" mental
         | health startups. A large portion of the affected population is
         | content being "mostly better, quickly" rather than "fully
         | better, slower".
        
           | d0mine wrote:
           | > medications are highly cost/effective..
           | 
           | You are commenting on the article that says that it is BS.
           | The most upvoted comment on the article at the moment says
           | "it [the ineffectiveness] is old news hardly worth
           | mentioning"
        
             | SkyPuncher wrote:
             | No, the article does not say this is BS. The article is
             | about a specific theory on anti-depressants. Not about
             | their ineffectiveness as a whole.
             | 
             | > Antidepressants are an effective, NICE recommended
             | treatment for depression
             | 
             | This fact remains. It's pretty well known in medicine that
             | we don't really know why anti-depressants work, but they
             | do. Different people react differently to different
             | versions.
             | 
             | This article is simply stating that the original "simple"
             | theory of "low serotonin" is not sufficient to explain
             | depression.
        
               | d0mine wrote:
               | Last time I've looked into it in any detail, there were
               | tendency for any effectiveness to vanish in repeated
               | studies (indistinguishable from placebo).
        
       | roody15 wrote:
       | Think we have known this for a while. For example Wellbutrin
       | (Bupropion) works well for many people and it doesn't work on
       | serotonin levels at all. In fact it causes an increase of
       | dopamine uptake in the brain.
       | 
       | Think increasing the dopamine levels causes a variety of changes
       | to complex systems in the brain that are not really fully
       | understood.
       | 
       | SSRi's also cause changes to underlying systems in the brain that
       | are not as simple as you are "low" on serotonin.
       | 
       | My two cents
        
         | y-c-o-m-b wrote:
         | I'm on Wellbutrin (lowest dose) and it works great. I have no
         | side effects whatsoever. Been on it since 2019. It's kept my
         | depression in check and even helps with my ADHD a little. They
         | say you can't drink alcohol with it, but I binge drink every
         | weekend (I _really_ love alcohol) with no problems.
         | 
         | SSRIs were an absolute train-wreck to be on; they made me angry
         | and violent. I was on them for 10 years and I honestly don't
         | believe it ever helped against depression. If I missed 1 day,
         | I'd get the infamous "brain zaps". It took me about 3 months to
         | taper off the damn things and it was a brutal 3 months. The
         | last one was in October 2012 and I will never take them again.
         | I did not experience any increase in depression either, so that
         | makes a stronger case for them basically be worthless for me.
        
       | pizzathyme wrote:
       | Based on this, can anyone explain what treatment should be
       | pursued if they are suffering with debilitating depression? I
       | have a family member on SSRIs and therapy.
        
       | gillytech wrote:
       | I'm seeing a lot of measured and thoughtful comments in this
       | thread. Unfortunately I don't think we can "science" our way out
       | of depression. Especially since these drugs have an inexorable
       | link to violence and suicide. Here's plenty of documented proof:
       | 
       | https://www.cchrint.org/pdfs/violence-report.pdf
        
         | jahewson wrote:
         | The document you've linked to is whacky propaganda from the
         | Church of Scientology.
        
           | gillytech wrote:
           | There's nothing but claims backed by facts in that document.
           | Your _ad hominem_ attack is not a valid argument.
        
       | InfiniteRand wrote:
       | In a lot of ways the study of mental illness is like the war
       | against cancer, you can expect perpetual expectations of miracle
       | cures being made while slow progress happens in the background
       | and major reverses of assumptions sporadically occur, and
       | therapeutically specific variants make big progress while the
       | majority of the disease is treated by blunt tools which do offer
       | some help but at a considerable cost
        
         | hirvi74 wrote:
         | Same with Alzheimers. We finally have medications to remove the
         | plaques of tau proteins, and... it didn't do shit.
        
       | [deleted]
        
       | [deleted]
        
       | fithisux wrote:
       | Like Vitamin D? Just take your pills and make us rich? If you
       | don't get better is because you need more pills.
       | 
       | Legal substitutions
       | 
       | Pills <-> Credit Cards <-> Vaccines <-> Supplements <->
       | Technocrats <-> Religion
        
       | Uptrenda wrote:
       | There are many people who are anti-psychiatry who would probably
       | still benefit immensely from treatment. My worry is that such
       | people will look at this and say: "see look, the psychiatrists
       | got it wrong. I was right to question treatment all along; Anti-
       | depressants don't work." But the message here isn't that SSRIs
       | don't work for depression. It's that depression is a complex
       | illness and can't be reduced to a single chemical deficiency.
       | 
       | Anti-depressants mechanism of action is more complex than
       | 'corrects a chemical deficiency.' I hope such people considering
       | treatment know that while theories may change as we learn more:
       | medications still have to be evaluated against real-world
       | results. So the effectiveness of a drug remains the same.
        
         | KennyBlanken wrote:
         | It's less a specific study and more that almost none of their
         | research is reproducible and there have been a number of
         | serious breaches of trust, like Prozac being widely prescribed
         | to kids and turning out to be horrifically bad for them.
        
       | tyronehed wrote:
        
       | jonnycomputer wrote:
       | Some expert reactions to paper:
       | 
       | https://www.sciencemediacentre.org/expert-reaction-to-a-revi...
        
       | Arubis wrote:
       | So...why do SSRI users self-report efficacy?
        
         | BrianOnHN wrote:
         | Correlation isn't causation. The serotonin effect may be a
         | symptom of the depression. Treating symptoms is sufficient
         | intervention for many.
        
         | carabiner wrote:
         | https://en.wikipedia.org/wiki/Placebo
        
           | kennywinker wrote:
           | When they test drugs, they test them against a placebo.
        
             | [deleted]
        
             | hackerlight wrote:
             | 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/
        
               | rando14775 wrote:
               | 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]
        
           | copperx wrote:
           | 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 wrote:
         | 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 wrote:
           | 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 wrote:
             | 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 wrote:
             | The mechanism of SSRIs is not well-described as "increase
             | serotonin".
        
         | simonsarris wrote:
         | 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 wrote:
         | It might be a different mechanism, like brain-derived
         | neurotrophic factor[1].
         | 
         | [1]: https://www.science.org/content/blog-post/how-
         | antidepressant...
        
           | [deleted]
        
         | JaceLightning wrote:
         | It's mostly a placebo
         | 
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299662/
        
         | PragmaticPulp wrote:
         | 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 wrote:
         | 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 wrote:
           | 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 wrote:
             | 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 wrote:
         | > ...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/
        
       | sidcool wrote:
       | I am torn between two schools of thought on depression and
       | anxiety. Some say it is a purely biochemical issue. Others say
       | it's more of a psychological one and can be addressed with
       | therapy and exercise alone.
        
         | padolsey wrote:
         | Why not both? We always seem to try to dichotomize and
         | categorize incredibly complex systems for some reason. Surely
         | there are many components to the symptom clusters of depression
         | and anxiety. Life circumstances can matter, exercise can
         | matter, neurological dispositions can matter. All at once.
        
       | tus666 wrote:
        
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