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.
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.
> 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.
I go through this process regularly when I have to put away groceries. I get progressively anxious about just leaving them on the counter, and it devolves into me ignoring them until I have to use them, by which time some of them are no longer usable.
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.
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.
Star Slate Codex (Scott Alexander) wrote that the evidence for such is basically non-existent. Thus such claims remain dubious at best. Though this was many moons ago, and things change. Do you happen to know of any research that supports this?
SSC also wrote a long article mildly trashing "The Body Keeps The Score" (which is truly excellent and important), with some very poor logic. He's not infallible.
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.
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.
Did the ADHD cause CPTSD or the CPTSD that you might already have from childhood neglect/trauma that you're not aware of/dismiss/paint as "not too bad" manifests itself as ADHD?
Distraction from pain is one of the most common ways we deal with pain when it's not possible to escape it (which is the case for children that suffer emotional abuse/neglect).
I should probably have said that I am self-diagnosed with (C)PTSD, and have never consulted a professional about it, then again I truly believe we will one day look at psychologist of today like they look at Freud and psychiatrist like blood-letters of the past.
This may sound wild and woo-woo snake-oil, but using cannabis products coupled with mindfulness/deep-thought, I am sometimes able to fire up my "mental debugger" and access parts of my subconsciousness that I cannot tap during normal sobriety. I can pull out memories that I had subconsciously blocked, but I am able to process them in a healthy, compassionate, and understandable manner.
> Distraction from pain is one of the most common ways we deal with pain when it's not possible to escape it
Probably explains my compulsive levels of video games and screen time as a youth, then again... I grew up on a small horse farm on the outskirts of society, so it's not like I had anything else to do lol.
I do sincerely believe that anyone that ever wronged me (especially my family) ever did anything intentionally. Parents aren't given a "Parenting an ADHD Child 101" course or anything. Hell, both my parents probably have it themselves, and my parents swear on their life that the school system never told them anything.
I do think my ADHD manifested first though, for a variety of reasons. A lot of signs and stories seemed to point that I was even symptomatic from infancy. If anything, I wouldn't be surprised if it were environmental. All my male childhood school friends that grew up in a <small distance> radius of me all received the same diagnosis at one time or another.
So, while I do think you are on to something, I do not think it applies to me directly.
RSD (Rejection Sensitive Dysphoria) is a factor in many cases. Overreaction to external stimuli makes rejection hit harder. So it doesn't need to be constant or even more negative feedback - the same will be worse even if you are coping and getting things done.
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.
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.
Well, first of all, I didn't say it was the only cause for depression; it's a condition that comes in lots of different flavors and this is only one.
Second, to elaborate a bit more, having to constantly manage your brain in order to get it to do what you need can be exhausting. Any success you achieve feels like it's extremely tenuous, and I'd say most AD(H)D people have had an experience of doing well for a while and then everything falling apart. So nothing ever feels safe. The negative feedback you get will tend to reverberate much more loudly in that environment than the positives.
I understand this, lol. But you can also take heart that you don't struggle alone. You might be surprised at how many places you can be open about this stuff and have positive things result.
Another complicating factor is that it is assumed that there are a few different subtypes of depression. For example with and without psychotic features. Another subtypes is the "atypical depression", which actually has, in contrast to classical major depression, "reactive mood" and a high degree of "rejection sensisitivity": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990566/
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.
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.
Hmmm, I know (C)PTSD can have issues that seem similar to ADHD, but then again, all these disorders are just a collection of symptoms slapped together. Is cyan a hue of blue or a hue of green -- does it even matter?
The only issue I have with emotional trauma-induced ADHD, is that it's very easy to be a chicken vs. egg issue. I have ADHD, and I experienced what I would consider emotional trauma to some degree (often because of ADHD), but which came first? It seems very cyclical to me.
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.
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.
“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.
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?
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?
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.
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.
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.
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!
> It doesn't sound like you have any direct experience of this
It doesn't matter if I have personal experience with this although I do. A very bad personal experience with the mental health service that was provided as well as the side effects I was talking about.
> I had to come off them and it wasn't a problem.
This just comes off as ignorant, there is established literature on the withdrawal effects. I was not speculating or spreading FUD. They are real, documented and more common than your anecdotal lucky experience
So your bad experience is data, my ok experience is anecdote and is worth less than yours. Gotcha.
'I had no problem' means that bad problems aren't inevitable, which opposed the totally unqualified 'SEVERE' claim - they aren't always 'SEVERE'. That doesn't discount anyone's experiences when things do go bad as I acknowledged here https://news.ycombinator.com/item?id=32169654 - I'm not dissing anyone's experiences.
You keep missing the point, there's a reason every doctor who prescribes these drugs will also make sure to taper you off because if you suddenly come off them there will be consequences. Now I'm not gonna troll the literature to figure out what the exact numbers are.
It's not about you dissing anyone's experience, it is about you ignoring the reality of this issue just because you were lucky.
Yes, they taper you off. This is to prevent the reactions being potentially SEVERE. In some cases they will still be SEVERE (yours), in other cases they won't (mine). I don't dispute that and I never did.
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.
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?
I don't think it is an isolated incident. Once something has become "known" among the public and the medical profession, it seems quite difficult to update it. Another example is the dietary cholesterol issue.
The human body is incredibly complex and we have quite limited tools to study it, so we are bound to arrive at wrong conclusions. That by itself is to be expected, but what does really worry me is this missing knowledge updating mechanism. It can take decades for quite a substantial update on what we thought we knew to trickle down from academia to practicing medical professionals.
At this point, if you have any kind of scientific literacy, it might be a good idea to verify whatever your doctor claims.
> It can take decades for quite a substantial update on what we thought we knew to trickle down from academia to practicing medical professionals.
A recent ep of the Trickle Down podcast (premium offshoot of a show that studies conspiratorial thinking, Q Anon Anonymous), discussed how we learned to treat ulcers with antibiotics and then lost that information for something like fifty years. Changing the scientific understanding of their cause had a Greek doctor going to his country’s health ministry over and over and getting rejected despite results. I think you nailed it.
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.
many illnesses are reproducible. you can give people viruses and they do indeed get sick. so i don't think you need to discount the entirety of medicine.
afaik, there is no reproducible causality for depression; we can't induce it. we only measure it's correlations and have % confidence in hypotheses.
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.
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.
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.
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.
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.
Sure - I should have given some sources in my original comment. The order of my list of purported mechanisms is also not really ordered by significance. I think generally, more and more mechanisms of AD efficacy are discovered, and it can seem that the more we know, the less we know. Additionally of course, there are like 15 different classes of ADs, with hundreds of different compounds in total. What we know for sure I think is that the serotonin and also the monoamine hypotheses of depression are highly oversimplified and even internally contradictory, and many more targets and way more general biochemical mechanisms in the brain must be involved in depression.
- One source covering the 5-HT1A autoreceptor downregulation part in particular there is "Serotonin autoreceptor function and antidepressant drug action" (https://pubmed.ncbi.nlm.nih.gov/10890313/)
- I personally like the books "Antidepressants" by Leonard (that the previous paper is a chapter of) and "Anxiolytics" by Briley and Nutt. These discuss really a wealth of observed/purported mechanisms, also for example including the significance of late gene products.
- Wikipedia: Pharmacology of antidepressants (https://en.wikipedia.org/wiki/Pharmacology_of_antidepressant...) has great sources, especially on the anti-inflammatory and immunomodulative pathways, and introducing HPA axis modulation as another possible pathway.
> 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.
> 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.
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.
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.
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.
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'.
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.
No ECT is most certainly the most efficacious treatment for depression we have.
Talking therapies have a respone rate in depression of circa 40% [0], probably just slightly higher for antidepressants up to about 50% and faster [1], ECT respone rate is well over than even for those with treatment resistance but as high as 90% [2]. Vitally, the reposnse to ECT is fast and is often under 10 days.
The fact that ECT is burdensome, limited in availability and stigmatizing (which is why it's got so much legislative structure around it) is not relevant for it's efficacy.
This is spelled out relatively well in the UK's Royal College of Psychiatry statement on ECT [3]
> ECT IS A FIRST-LINE TREATMENT FOR PATIENTS ... where a rapid definitive response for the emergency treatment of depression is needed
This is because it works quickly and reliably to treat depression.
I think we're just disagreeing on different interpretations of the word effective.
If something works, but has so many negatives that you only use it when other negatives outweigh those, then it's effective in some sense of the word, but I'd maybe not phrase it as "the most effective treatment".
Kind of like pre-emeptive mastectomy for breast cancer, it's effective and it's the recommended treatment for people likely to have problems due to specific genetic factors, but saying "pre-emptive mastectomy is the most effective treatment for breast cancer" is missing a lot of important nuance and can sound extreme, even though it could be defended as a true statement.
> I think we're just disagreeing on different interpretations of the word effective.
That's likely. I'm using the word in the sense of clinical efficacy, i.e. how likely an intervention is to produce the intended outcome. In this case the response rate to the intervention in those with depression [0].
Preemptive double mastectomy is the most effective way to date to prevent breast cancer [2] (~95% reduction). This is important for those at heightened risk, for example those with pathological variants of BRCA 1 & 2 which each independently increase the risk of breast cancer 5 fold (up to 70%!)[1]. Coupled with other factors some women are statistically almost certain to get breast cancer if they live long enough.
We can't mince words with peoples lives. People with severe depression deserve to know that ECT is a safe treatment and the most effective treatment available. And there should not be stigma in any treatment.
Similarly, pre-emptive mastectomy the most effective prophylactic intervention available for preventing breast cancer. And important for those who are at very very high risk.
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.
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.
> 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.
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.
> 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.)
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).
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.
How would you describe a condition like Bipolar Disorder where the brain swings in both directions? Depression is half of Bipolar, but is the brain broken in this case? What about the manifestation of psychotic features?
Based on my understanding of the condition, typical anti-depressants tend to be a contraindication for Bipolar Disorder (can induce mania), so in some regards it seems like the medications not only work for Bipolar, but they work a little too well.
If depression is not a disease, is Bipolar a disease -- half a disease? I am curious what you think. I do not suffer from BP, but I was misdiagnosed with it at one time (I never had psychotic episodes or anything), and doctors wanted to load me up with medications. Luckily, I refused, and I later found out that wasn't the issue, which caused me to lose a lot of faith in psychology/psychiatry. However, the whole process made me more empathic to those with the disorder.
A childhood friend of mine developed schizophrenia at 25, so I am surely convinced of the existence of true mental illness. To me a mental illness is defined as a clear defect in the workings of the brain, such that you have uncontrollable hallucinations and mania. I am not as familiar with bipolar disorder, but my overall argument is not that mental illness is non-existent, it's that depression is either vastly over-diagnosed or should not be categorized in the same group as schizophrenia and the like. Where is the line between "I've abused my brain with the comforts and overstimulation of modernity and now I am not happy" with "I was born to be sad because I'm genetically broken"?
In the end psychology is just too political and too lacking in scientific rigor to handle these questions. the DSM is essentially a politically motivated group of academics voting on what is or isn't a mental illness. At one point homosexuality was a mental illness, seen as a deviance in brain function leading to the end of reproduction. But the political tides changed and now it is no longer classified that way. How can we drug people for a lifetime based on the changing tide of academic bureaucrats who vote on what is or isn't normal? Is it too cynical to believe that the pharmaceutical companies making massive profit off of the mental health drug industry are not backing the psychologists making DSM decisions?
A kid comes in saying he's depressed all the time. They ask him what's wrong, why he is unhappy? He complains about feeling sad all the time without reason. They give him anti-depressants. But what about the fact that he plays video games all day, watches porn constantly, is on booze and weed and stimulants, is constantly browsing novel media on his smartphone, constantly entertained with netflix, he's blasted with supernormal stimuli 24/7 and then wonder's why his brain chemistry is out of whack... yet the mental health industry would rather see him drugged up on profit making anti-depressants rather than struggle through the years of effort and therapy to change his lifestyle.
>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.
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.
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.
> 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.
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.
It seems to work, by definition, but I don’t think this approach qualifies as science. For a theory to be science, there has to be at least some mechanism. This is just statistics.
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.
> 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.
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.
"Low serotonin" was a marketing simplification at one point a decade or more ago. Whether companies were the source of that simplification is up in the air, but they certainly leaned into it in their marketing.
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.
The uncomfortable feeling you get from 5-HTP can be from activation of parasympathetic serotonin receptors, as well as activation of 5-HT2C in the brain. You're essentially going through the initial two weeks of SSRI use, where 5-HT2C gets activated but hasn't downregulated yet, which is a hypothesized source of increased anxiety and suicidality from initial SSRI use. What would be interesting is to see if that discomfort would dissipate after 2+ weeks of chronic 5-HTP use, with the goal of blasting 5-HT2C until it's desensitized, which is what happens with chronic SSRI use. I don't like the idea of 5-HTP because of the potential for higher levels of serotonin in the blood potentially activating 5-HT2B in the heart, potentially leading you to need a heart valve replacement.
Regarding L-Dopa, from what I'm aware of, L-Dopa gets metabolized before it makes it to the brain, so much of the L-Dopa gets metabolized into dopamine and norepinephrine outside of the brain and then those neurotransmitters activate the parasympathetic nervous system, resulting in increased anxiety, paranoia and physical discomfort. That parasympathetic activation can increase feelings of alertness and wakefulness without ever having L-Dopa enter the brain. Another interesting thing to see is how L-Dopa would fare when taking it with an inhibitor that would allow it to successfully enter the brain a la Carbidopa for Parkinson's patients.
Obviously don't do this, I'm just thinking out loud and fucking around with your body like this can have serious consequences if you aren't doing so under the supervision of your own doctor.
Finally, regarding THC, if anxiety and paranoia are problems for you, like you allude to when talking about L-Dopa, try delta-8-THC. I find it to be much more therapeutic than delta-9-THC. I get no anxiety or paranoia from delta-8-THC, but I do get the full therapeutic effect I got from normal THC when it comes to antiemesis, mood, pain, etc. It also has less of an intoxicating effect, and doesn't mess with my memory of motivation as bad as delta-9-THC does. I haven't used normal THC in years despite it being legal and readily available.
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.
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.
Have you ever tried 5-HT2A antagonists or inverse agonists like trazodone, mirtazapine, or the dozens of atypical antipsychotics that are indicated for depression? I ask because I wonder if the rapid tolerance at 5-HT2A is responsible for the therapeutic response you get from psychedelics, and if antagonists or inverse agonists can emulate that tolerance in a sustainable way that doesn't require regular psychedelic experiences. Those experiences can be great, but the potential for bad experiences might be a Faustian bargain.
> 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…
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.
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.
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.
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.
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.
It was likely a combination of several things. I had moved to a new country after high school for college. The college also happened to be in an extremely cold part of the country, and I joined in the winter semester.
Culture shock, being alone in a new country, seasonal affective disorder (I come from a warm tropical country), being in a long distance relationship - they all likely contributed.
I also made some pretty bad career moves immediately afterwards, which likely didn’t help.
>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.
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.
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
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.
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.
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.
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...
Escitalopram is specifically prescribed for anxiety disorder at least in my country of residence. I think it’s considered one of the top options for GAD/panic disorder generally.
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.
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.
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.
>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.
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?
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
> 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.
> 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.
> 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.
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.
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.
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.
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.
There are many, many, many pharmacy drugs that can stop suicidal thoughts fast and don't have the track record of the "modern antidepressants". Long, long, long track records. Small dose lithium and lamotrigine come to mind right away. But how they work--nope, not clear. Okay, we'll agree it's not serotonin, how does that help us? Would it help if American doctors could prescribe 3 weeks for a spa holiday like European doctors? Maybe, for low-level depression, but not for suicidal thoughts, that just won't cut it. There is bipolar I and bipolar II and so big differences. Schizophrenia, big difference. But again, knowing that it isn't serotonin, that's nice, now what?
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.
> 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.
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)
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.
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.
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.
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.
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.
I'm sure they do but I only have anecdotal evidence from people that tried a number before the "ahaaa" moment.
I don't take them (well, except for sleep with a low dosage of Trazadone (which I can't anymore because it gives me priapism) and mirtazapine(which made me sleepy even the next day)), but my experience is with stimulants for ADHD.
I've tried quite a few stimulants and while all worked for my ADHD (heck even pure nicotine works somewhat), some combinations were brilliant but illegal, and metylphenidate (Concerta) does an amazing job for my impulsivity and an ok-ish job for my focus.
Sure, I can't just snap my fingers, pop some low dosage meth (and I need to stress low dosage -- 15-20mg) or my favorite (3-1 isopropylphenidate + metylphenidate) and enter a flow state at will, but Concerta just changed my life for the better.
I'm sure that a lot(most) of people with depression just as with ADHD need more than just the medication.
If you're depressed because of your circumstances and have 0 power to change them, perhaps anti-depressants work less well, but I've read about numerous people who had a purely "chemical" depression -- there was nothing "bad" about their life and they changed nothing and after anti-depressants they were just not depressed anymore.
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.
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.
> 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".
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"
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.
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.
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…
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.
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).
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.
> 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.
It seems like you didn’t really read it, just the initial list of claims that he addresses.
> 5. The effect of antidepressants only becomes significant in the most severe depression – Everything about this statement is terrible and everyone involved should feel bad
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.
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).
> 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.
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.
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.
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
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.
- 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
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.
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“.
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.
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.
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?
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.
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?
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") .
This site has an unbelievable amount of armchair-science that gets rattled off. You are right, because depression and anxiety are primarily biological phenomena.
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.
>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.
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.
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.
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.
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.
This reminds me a lot of Mark Fisher and Capitalist Realism. Obviously if the article is true then who is to say about low serotonin levels, but in any case "It goes without saying that all mental illnesses are neurologically instantiated, but this is nothing about their causation if it is true, for instance, the depression is constituted by low serotonin levels, was still needs to be explained is why particular individuals have low levels of serotonin. This requires a social and political explanation; ... This pathologization these problems - treating them as if they were caused only by chemical imbalances in the individuals neurology and/or by their family background - any question of social systemic causation is ruled out."
In essence a liberal worldview is not equipped to deal with mental illness.
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.
> 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.
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.
>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.
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.
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.
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?
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.)
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.
> 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.
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.
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.
It isn’t someone’s personal/unique suffering that I am invalidating. They are saying that we are having uniquely depressing times _in general_ which if you take a brief look at history is laughably invalid.
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.
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.
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.
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.
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.
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.
whats really interesting is, while some things like electronics and automobiles etc have been getting cheaper, intangibles like healthcare and education have been increasing in cost... whats the cause?
Obviously, I don't know the full story, but one thing the three things I named have in common is relatively inelastic demand. In the case of education and healthcare, I suspect Baumol's cost disease is also a factor.
Cars and other manufactured goods tend to get cheaper over time because they can take advantage of economies of scale, as well as global supply chains and free trade. We're seeing that very concretely right now as the global chip shortage has put pressure on the used car market.
Education, housing, and healthcare are largely unaffected by free trade, and Baumol's cost disease is literally a statement about how certain industries cannot take advantage of economies of scale.
Come to think of it, let's also toss childcare in the bucket of "things that have gotten more expensive faster than inflation over time" since, among households with children, we have a predominance of households where all parents who are present work. Again, we have inelastic demand and Baumol's cost disease rearing their ugly heads, so maybe there's something to this theory.
TV and automobile manufacturing are a lot more productive than they were 50 years ago. A teacher can still only teach one classroom at a time.
Therefore, service industries like healthcare, education, and even construction get less and less efficient relative to manufacturing and production industries, which enjoy massive increase in efficiency year after year. This is partly why an 80 inch 4K TV is eventually going to cost $500 and a 4 year college education is going to cost $500,000.
if i understand it correctly, its supposed that overall wage increases mean other industries have to compete to get/keep workers but they dont have effeciency increases like manufacturing so prices continue to rise
it makes logical sense, but i wonder if it really is wage competition causing this when wages have been mostly stagnant for the past 50 years?
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.
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.
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.
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
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.
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.
> 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.
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.
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.
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.
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."
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.
Weren't a lot of towns built basically surrounding a castle?
I guess people in towns would see wealthy people often, but people in remote farms and villages wouldn't.
I'm not sure exactly what wealth is being rubbed in my face today. News about rich people? I would assume there would also be news and gossip about rich people back then too.
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.
How would you "medically disprove" the notion that some people are unhappy because the circumstances of their lives are bad rather than biological defects?
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.
“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.
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.
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?
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.
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).
> 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.
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.
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.
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.
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).
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.
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)
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.
Thanks! Yeah you shouldn't feel bad - rich people are a good example, and I would expect them to have a lot more resources to escape depression in general
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.
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.
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.
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!
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.
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.
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.
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.
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.
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.
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:
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.
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
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?
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
"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.
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.
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.
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.
This study shows (decide how convincingly) what has been suspected anyway. The causal direction of “chemical imbalance leads to depression” is just not a sensible assumption. SSRI are of course able to alleviate the symptoms as are other drugs or treatment that are not associated with serotonin. Tricyclic antidepressants, sleep deprivation, transcranial magnet stimulation, ketamine, exercise and many more. Also the efficacy of these other treatments does not depend on the performance in the Forced Swim Test. The multitude of different antidepressant approaches, the different and heterogeneous animal modeling leads me to believe that what we describe as major depression is a pathological alteration in the brain subnetwork activations, probably between frontal brain areas and formatio reticularis/pons. SSRI are a roundabout way of influencing network changes that take time to develop. And these chances happen to work via Sertonin paths but serotonin is not necessarily the cause of “depressed” state of the brain network.
Disc: Only peripherally me area of expertise. No sources because mobile
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.
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.
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.
> ...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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
> 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.
> 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.
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.
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.
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.
> 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.
> 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.
> 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.
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.
> 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.)
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.
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.
> 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.
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".
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.
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.
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.
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.
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.
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.
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.
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.
I hear you. The ignorance around ADHD is appalling. My medication (Elvanse) works wonders - being able to focus like normal people has entirely changed my life.
I remember the first time I took one of those pills, I was astounded my how clear my mind became. It was like the noise switched off, and I could just get on with what I needed to.
Like you, I was diagnosed as an adult. I have considerable regret for all those years prior wasted without diagnosis and medication. I'm trying to undo all the maladaptive behaviours I've developed likely because of this, and shed myself of the many, many guilts I feel. But it's a long hard slog.
I wish my parents were still alive so I could talk to them about it all, and show them the person I've become since.
When I see confident expressions of ignorance about ADHD, or even worse, scammers and liars trying to take advantage of people with ADHD, it also makes me see red. You're not alone in this. I think you were right to speak out here, whatever anyone else says.
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.
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.
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.
> 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.
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.
> 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.
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.
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.
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.
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.
Stop eating carbs, go out and get sunlight. Do mild but regular exercise. I got at least three people of AD medication with this and feel much better myself.
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.
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?
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".
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.
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.
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
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.
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.
There's one cause that is really hard to detect (unless you're informed about it) and that I suspect is behind a lot of people with depression. In fact it took me decades, and only by chance did I realise what it was:
Emotional abuse / neglect, especially the one that occurs in childhood.
* You feel something in life is lacking but dont know what, or blame yourself for it, or look for it in in thrill seeking activities, or through buying stuff to fulffill this emptiness, or you escape from this ever present painful feeling with addiction (hint of what that thing is: being really loved, not romantically loved, but actual unconditional love, the one that only healthy parents can give and which you feel in some way when you have a community behind you. Partial love given by a lot of people ends up almost feeling like parental unconditional love.)
* Can't seem to make friends, or make friends but don't seem to connect at a deep level and end up feeling lonely anyway.
* Also the cause of social anxiety.
* Burnouts due to lack of boundaries (which also come from abuse). Feeling like you put others first all the time, and end up feeling somewhat fake.
* (...)
All of these can lead to depression. And they all have the same root-cause. And barely anybody talks about this (unless you go really looking for these communities, but unfortunately they're not really mainstream).
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".
> 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.
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.
> 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.
> 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.
> 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!
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.
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.
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.
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.
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.
Hardly. Profiles are extremely minimal, and it's not much more fleshed out than the average WordPress comment system is. I can't follow people on HN (AFAIK) either.
Agree that being able to choose who you follow/"friend" is a key social media feature missing on HN. But profiles are not noticeably more minimal than those on Twitter are far as I can tell.
> 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]
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.
> 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.
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.
". . . 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!
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.
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.
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.
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.
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.
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.
You might be interested in reading Tribe by Sebastian Junger. The thesis is that a lot of this is caused by the destruction of community and shared purpose in modern western society, but I think he'd push back strongly on the rigid structure being important or even beneficial.
A primary example in the early parts of the book are anglo settlers who joined native american tribes either voluntarily or by force. They almost universally preferred their new lifestyle and if brought back into white society would frequently try to escape. The reverse pretty much never happened.
> 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.
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.
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.
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.
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)
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.
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.
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.
EDIT to king_magic: man I don't know what your deal is. I bet it's really good on paper. Just not as good in living it out, hence depression.
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I wish I could press a button on the user interface to talk to someone in person. Real life. You and I. Real Meat. In person. king_magic and daniel-cussen.
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.
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.
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.
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
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.
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.
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?
> 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.
> 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
I sincerely do not think it is an “extreme personal skew” to reject any perspective which would either casually or gladly leave me dead, nor that there’s any reasonable assessment which would arrive at that conclusion.
”I reject perspectives which render me dead” is a very middle of the road personal skew. It’s a personal skew which would be extreme in absence. It’s the kind of personal skew which alarms people that something is wrong.
If you think it’s “extreme”, because the kind of conversation you want to encourage here is “light”, then you ought to know that the kinds of “light” comments I routinely get here—about medication which means the difference between crippling anxiety that made life not worth living, and about a diagnosis which made changing that accessible to me—those comments don’t just vanish because they get moderated. They wouldn’t just vanish if I didn’t have “show dead” in my settings. I seldom see the moderation until after people have laughingly dismissed anything about my experience, they vanish after my reality has been not just questioned but lightheadedly treated as a butt of a joke.
It isn’t just about “the internet” being “wrong”. Discussions that happen anywhere can lead to people making irreversible decisions. “The internet” isn’t some abstract thing, it’s real human beings interacting as quickly as requests are processed.
My personal experience isn’t unusual. Other people will encounter comments like I’ve received and some of them will be discouraged. Some of the consequences of that will be dead humans who wanted to be alive. Pushing back against that isn’t just personal to me. It’s my way of hoping that other people who experience what I have stay alive.
If that’s “breaking the rules”, fucking ban me because I want no part of it.
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.
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.
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.
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".
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.
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.
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.
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.
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)
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.
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.
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
"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.
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.
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).
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?
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.
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.
> 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).
> 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
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).
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.
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.