12 ms·

Schizophrenia drugs may have been off target for decades, study finds

146 points by thedday 3y ago

M1ch431 3y ago
The entire paradigm for treating schizophrenia and other chronic mental states is flawed. Mental distress/disorder cannot be treated properly because of the strong for-profit motive (unrestricted greed) that these privately-owned (sometimes publicly traded) mental hospitals and pharmaceutical companies have. Mental hospitals are effectively a prison. Locked doors, removal of rights once committed, coercive and sometimes forced treatment and restraints, being told that you have a lifelong disease (with no measurable physical damage -- fMRI scans are not indicative of damage) that needs drugs for the rest of your life, and getting billed an exorbitant amount - to name a few things that are wrong. If your rights are violated and you are declared incompetent (which is pretty common if you are unstable or in crisis), it's an uphill battle in special courts called Mental Health Courts. It's difficult to get a second opinion from a third-party psychiatrist, or to contest treatment orders (such as mandatory intramuscular antipsychotic injections or ECT which respectively have a very potent and long-term effects). The conversation needs to be shifted towards the Soteria House paradigm. This article sums this model of care pretty well: https://www.madinamerica.com/2019/09/soteria-house-heal/ https://www.madinamerica.com/2019/09/soteria-house-heal/ They have very impressive results, particularly in regards to schizophrenic and psychotic patients, and do not use life-long tranquilizer prescriptions to achieve their results. It needs more study, it needs more implementation, but the core of the model is that it builds a supportive community around vulnerable people -- instead of caging and viciously profiting off of these people. I spoke on this matter in the past, and you can read my thoughts here: https://news.ycombinator.com/item?id=34029719 https://news.ycombinator.com/item?id=34029719
leon_theremin 3y ago
[flagged]
canistilkehese3 3y ago
It's important to keep in context that none of hepsteens clients were persecuted or even publically named, and the people connected to them take a percentage of every profit you work to generate. Don't call them out on that though, these sedatives will fuck you up.
A_D_E_P_T 3y ago
Situation normal. Consider the discovery of valproic acid: "Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder." To this day, nobody knows exactly how it works, apart from the fact that it hits more than a few targets. (And it's a particularly potent inhibitor of the epigenetic modulator histone deacetylase.) Apart from a subset of very clear-cut cases -- steroid hormones, peptide hormones, and certain aggressive chemotherapeutic drugs -- there's no clear model for most small molecule drugs. Even really mundane ones like metformin and paracetemol are very imperfectly understood.
- aatd86 3y ago
  Normal might be a strong word. It messes with the brain which is the core. Goes to show a lot of clinical medecine is about short-term relief and not necessarily about real health. If you really look at it with unbiased eyes, between elective surgeries and what not, it's not really about curing any true dysfunction sometimes. Perhaps too many times. We just go with the flow but, heck, MDs are not even necessarily healthier than you, some even smoke to this day! Go figure...
  - crooked-v 3y ago
    You've gone off on an unrelated tangent here. "Situation normal" in this case means that, as with lots of drugs, we only poorly understand the mechanism by which they actually work, and that new discoveries can completely change our understanding of how to use and improve on them.
    - aatd86 3y ago
yuck39 3y ago
Link to the actual paper: https://www.nature.com/articles/s41593-023-01390-9 https://www.nature.com/articles/s41593-023-01390-9
gvb 3y ago
https://archive.ph/sZerh https://archive.ph/sZerh
whats_a_quasar 3y ago
The brain is really complicated, and all psychiatric medications affect multiple receptors and subsystems. Framing this study as "antipsychotics were off target" is an editorial choice. The title could just as easily have been "Improved understanding of antipsychotic action means we may be able to design better antipsychotics." Edit: It also ought to be noted that the study was on mice that had been given amphetamines to mimic psychosis. Which is interesting and good science, but seems far from enough evidence for the press to write stories with headlines like "Everyone Was Wrong About Antipsychotics" or "Schizophrenia Drugs May Have Been Off Target For Decades, Study Finds." This sort of internet story bothers me because I've spent time around schizophrenics who are recovering from a psychotic episode. Schizophrenia can get really, really bad, in a way that I don't think most people who haven't had contact with the psychiatric medical system understand. Antipsychotics have awful side effects, but for many people the alternative is uncontrolled psychosis, which can be vastly worse. There's a decent chunk of people who inherently and vocally dislike psychiatric medication, and these media stories are in that tradition. But the only people who ought to be involved in the decision about using antipsychotics are the patient, their family, and their medical providers. Writing headlines that are too broad for the evidence that supports them does not help improve the lives of people with schizophrenia.
- Lutger 3y ago
  This media story isn't 'in the tradition' of vocally disliking psychiatric medication. You could twist the headline to be, possibly. Have you read the article itself? Its the complete opposite. The headline is a bit attention grabby perhaps (and of course, that is what a headline must do), but I wouldn't even call it clickbait. It is even fairly accurate. Yes, they were likely off target with the specific neuroreceptors, no that doesn't mean the medication didn't work and of course, this is a positive development for designing better medication. This is classic storytelling, draw the reader in with some conflict and save the resolution for the end. We need to be able to discuss negatives and limitations associated with psychiatric medication in an honest and nuanced way. They often don't work well enough, there are costs associated and just giving somebody a pill and be done with it is hopelessly inadequate to the point of negligence. As someone who did experience uncontrolled psychosis myself, let me tell you the absolute taboo of discussing these matters made me way more uncomfortable than the side effects. Furthermore, psychiatry made me feel like a diseased animal at times, not to be taken very seriously and just put on drugs for life to be on the safe side. In hindsight I do appreciate how difficult that line of work is, doesn't change my experience. I am not against medication really, actually I think they are a must-have. I just think most anti-medication people are not really rallying against the side effects or at least not initially, but grew opposition out of bad experiences with treatment that focuses only on medication and was just very inadequate. Medication is what represents that. Additionally, medication can come to represent your loss of sanity and with that, you fundamental not-belonging to the group of 'normal people'. Thus the desire to not be on meds 'for life'. Haven't spoken to a single therapist or psychiatrist who made me feel that was a legitimate desire and who understood that. Maybe things have changed, this was a long time ago. To deal with the resentment against meds, I think it is way more effective to address those concerns directly and without fear, rather than putting down everything that might be interpreted as negative about medication. Like you say, without experience yourself, you have no idea how bad psychosis can get. It is a really complex thing and you will need much, much more than pills. And not only for the psychotic episodes, because these experiences tear at your identity as a human being. It isn't over when the psychosis is over.
rybosworld 3y ago
It's amazing how far the medical world has come in treating ailments of the body, but we've made comparatively little headway in ailments of the brain.
- toasted-subs 3y ago
  There's a million reasons why. And I can't get into it without being called a quack. And yes, washing hands is common practice now.
- whatscooking 3y ago
  We haven’t gotten far at all. We treat symptoms, not diseases
- FollowingTheDao 3y ago
  Last I checked my brain was part of my body. And that is why so little headway has been made, people keep thinking the body and brain act independently of each other.
- pixl97 3y ago
  If instead of saying brain you say "The most complicated structure found in the known universe so far" it starts to make a little more sense on the enormity of the problem at hand. Most organs are composed of one or only a few types of cells and their particular arrangement doesn't matter that much. For example swapping kidneys between people doesn't change who they are (mostly, smaller edge conditions apply here). But we can't swap brains because the brain encodes your 'youness'.
  - BurningFrog 3y ago
    You can also think of "the brain" as a collection of 10-20 separate organs, rather than one super complex one.
    - pixl97 3y ago
      While true, the complexity of each organelle in the brain is still much higher than that of the typical organ elsewhere in the body. That and there is a high degree of connectivity and feedback between components where the API is completely and totally undocumented. It's not that you don't know what the known API calls do, you don't have any clue on how many API calls there even are. Accidently emulating one of these calls when attempting to trigger a different behavior can lead to wildly unexpected outcomes.
merricksb 3y ago
Same study discussed previously: https://news.ycombinator.com/item?id=37057135 https://news.ycombinator.com/item?id=37057135 (50 points/3 days ago/51 comments)
Aurornis 3y ago
The study used a mouse model where amphetamine is used to simulate schizophrenia. Obviously, it's not guaranteed to map to real humans having real schizophrenia. That doesn't mean it's a useless result, but everyone should remember that research is an accumulation of decades of many little pieces of information. This is another clue, not a "nail in the coffin" of old theories. The ultimate evaluation of medication is how well it actually performs in studies. If someone can develop a new medication that is more selective for D1 and show that it performs better and/or has fewer side effects then this would be a great result. However, don't get too excited. The pharmaceutical industry is often 10 steps ahead of public findings like this. A selective D1/D5 antagonist with negligible D2 affinity has already been trialed for schizophrenia without good results: https://en.wikipedia.org/wiki/Ecopipam https://en.wikipedia.org/wiki/Ecopipam Many of the most prescribed schizophrenia medications already have significant D1 affinity, too, so it's not really correct to say that we're "off target" These findings tend to be very aggravating to computer scientists who are familiar with systems that (mostly) obey clear-cut rules and can examined in extremely fine detail with enough equipment and motivation. Neuroscience is not so simple, but that doesn't mean it's all wrong. Each finding is one more piece of the puzzle.
- fragmede 3y ago
  While everyone should be keenly aware the limitations of taking experimental results in mice and extrapolating to humans (aka, they often don't), doesn't that mean what we really have, is a bunch of well tested medication for meth addicts? Which; if there was a way to get meth addicts off meth, would be a boon?
  - monknomo 3y ago
    It's not for addiction, but yes, if someone takes enough meth to induce psychosis, antipsychotics will reduce the psychosis.
  - edgyquant 3y ago
    Not necessarily addicts. You don’t have to be addicted to achieve psychosis you just need to take a certain amount. For me this amount is pretty small, I was prescribed adderal for awhile and even 20mg was enough to induce serious paranoia and the occasional hallucination
justsomeguyhere 3y ago
So I've tried half a dozen antipsychotics, here are my 2 cents: The only things those drugs did to me were making me comatose, poop my pants, sleepy, dumb and hungry. You can't be declared psychotic or paranoid, when the only thing you can do is sleep, drool, poop yourself, and make 3 words sentences, so lazy doctors think these drugs work. But they don't, there was zero change in my beliefs, fears, anxieties, I was the exact same person, only slower, dumber, and sleepier. And at some point, when you're exhausted from being a zombie, you end just lying to your doc and pretending everything is fine, even when you believe doctors should always know the truth, because it's the only way to stop yourself from staying a brain dead zombie for life and causing irreversible damage.
- winocm 3y ago
  Concur. Those medications ruined my life.
- tredre3 3y ago
  I recognize myself very much in your words. I've also tried everything and it does not change my beliefs, fears, crippling anxiety one bit. Let alone improve my mood. Thankfully does help with mania. But the side effects are pretty bad and the doctors I've met tend to dismiss them, especially the more esoteric ones. So I have to lie to doctors to steer them towards the care I really need. I would prefer not to lie. I tried not to lie. But when you tell them you want to quit or go as needed, they gently suggest committing you or lose interest in you. They see you as a toy to experiment on. It's impossible to be treated like an adult. It's infuriating.
- thrw238592 3y ago
  [dead]
  - kayodelycaon 3y ago
    You do need to be careful adding vitamins and supplements without medical guidance. For example, magnesium can interact with medications. I can't actually take it because there isn't a safe, reliable time in my daily medication schedule for it.
winrid 3y ago
One of the more popular Schizophrenia drugs also cause diabetes :(
- psychphysic 3y ago
  One?! It's pretty much all second generation... Metabolic side effects could probably be used to define SGA!
- Pixie_Dust 3y ago
  > One of the more popular Schizophrenia drugs also cause diabetes :( Not to mention, weight gain leading to type two diabetes, thyroid problems leading to fluid retention in the legs and memory loss. Not much of a cure :(
robinduckett 3y ago
I know someone who has diagnosised but untreated schizophrenia. She was admitted to the hospital after she started having thyroid problems and they also administered schizophrenia medication while she was in. The change in her behaviour was positive and dramatic and allowed her to start accepting help after being scared that men in white coats would take her away if she ever let on about her illness to anyone. Now she has been out of hospital for a while, unmedicated again and back to her old behaviour including talking to people who aren’t there and having bad episodes. Maybe some medications are off the mark but whatever they used for her absolutely worked. I realise a sample size of one anecdotal piece of evidence is hardly scientific, but I’m getting rather tired of the constant mouse model studies, with barely related parameters. I wish there was a better way to do medical research, in actual human beings. Unfortunately it seems historically that actual human medical research is mired in the suffering of the (generally unwilling) participants.
- P_I_Staker 3y ago
  [flagged]
  - ChrisClark 3y ago
    > Now she has been out of hospital for a while, unmedicated You're wrong, it obviously worked. Might want to check into your own beliefs about why the doctors are trying to sap all your bodily fluids.
    - P_I_Staker 3y ago
      I don't think you read my comment. This issue is actually highly contentious. If a remedy consistently has poor results, it's a bad remedy. Simply saying "it works for the ones that are righteous" is absurd. If you break it down that's generally what people are saying, but usually use words like lazy, stupid, crazy, addict, etc. If most patients can't or won't follow a treatment maybe it doesn't work so well. > Might want to check into your own beliefs about why the doctors are trying to sap all your bodily fluids. This is very insulting, and demeaning, not to mention untrue. At no point did I imply doctors are trying to sap me of my "bodily fluids". I've never believed anything close to that. A leach sucks body fluid, so I guess it's a bit like that, but metaphoric. You seemed to care about your friend. I don't see the point in blatant bigotry towards mental illness.
psychphysic 3y ago
The pharmacodynamics of antipsychotics is such a rich topic, yet this article is so crap! Surprised no mention of pimavanserin (which doesn't act on dopamine useful in those with Parkinson's and psychosis) and that L-dopa can reliably induce psychosis (used on Parkinson's).
tcj_phx 3y ago
Strictly speaking, psychosis is more strongly related to excess serotonin, 'the molecule of stress and inflammation'. Doctors sometimes recognize 'Serotonin Syndrome' in their ER patients: "too much serotonin causes signs and symptoms that can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever and seizures)." Usually the Serotonin Syndrome is caused by a combination of prescriptions, or street drugs. https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758 https://www.mayoclinic.org/diseases-conditions/serotonin-syn... All the effective anti-psychotics seem to have anti-serotonin properties, in addition to their anti-dopamine effects. For example: "there are also recent studies that 'stumbled upon' the 'shocking' evidence that anti-dopamine drugs commonly used for treating schizophrenia such as haloperidol are actually potent serotonin antagonists as well." - http://haidut.me/?p=1297 http://haidut.me/?p=1297 One of you quoted my essay Cargo Cult Psychiatry in a comment on Sunday, on a submission of Feynman's Cargo Cult Science. I responded, then thought to submit my link to the original at Mad In America again: https://news.ycombinator.com/item?id=37110874 https://news.ycombinator.com/item?id=37110874 This paragraph from that comment is essential for helping anyone diagnosed with the label of "schizophrenia": "The good news from the mental health world is that Chris Palmer, M.D. published Brain Energy [0] last year. I haven't read more than excerpts from google books [1]. My understanding is Dr. Palmer was a conventional palliative psychiatrist, then he had a patient whose schizophrenia improved on a ketogenic diet. The patient was able to discontinue antipsychotics: Dr. Palmer's mind was blown. Then he discovered the 70+ years of research establishing that mental health conditions are metabolic problems that can be successfully treated with pro-metabolic therapies. Perhaps the most bold and disruptive aspect of Brain Energy is understanding precisely how and why medications that harm metabolism might reduce mental health symptoms. The long-term consequences are of great concern and require the urgent attention of the psychiatric community. -Chris Palmer, MD - https://twitter.com/ChrisPalmerMD/status/1687850270602981376 https://twitter.com/ChrisPalmerMD/status/1687850270602981376 [...] [0] https://brainenergy.com/ https://brainenergy.com/ / [1] https://books.google.com/books?id=FoxlEAAAQBAJ&pg=PT233&dq=B https://books.google.com/books?id=FoxlEAAAQBAJ&pg=PT233&dq=B "
- psychphysic 3y ago
  pimavanserin case in point
11235813213455 3y ago
I was diagnosed with schizophrenia, given some strong antipsychotics, it was a disaster I could barely talk or hand-write properly, gained 15kg. Fortunately I didn't listen the advices and stopped after 4 months, my therapy now is just walking, running, cycling, outdoor, trees, vegetable, minimalism
- tredre3 3y ago
  > Fortunately I didn't listen the advices and stopped after 4 months, my therapy now is just walking, running, cycling, outdoor, trees, vegetable, minimalism Over-medication is a big problem, but you have to recognize that you are extremely lucky to be able to function without it. Not everybody can. I couldn't. I share your experience regarding side effects, it would likely kill my career. Thankfully anti-psychotics work quickly, unlike antidepressants. As long as I have the discipline to recognize the signs, I can medicate mostly as needed. But this, again, is a privileged situation. More severe cases can't risk that "as needed" treatment.
  - 11235813213455 3y ago
    Right,my case is light (I've always had a job, at least between major burnouts), and the injections were way too big for my weight. It was efficient as I was calm at that moment, I started reading books again, but I lost all my passion for things, my brain was like mostly turned off, that's why I preferred returning to the previous state and finding other solutions
- m_0x 3y ago
  Pardon my ignorance and prejudice, but how are you not a danger to the people that surround you? Or is schizophrenia a spectrum very much alike as autism?
  - FollowingTheDao 3y ago
    hey, that was a pretty, uh, stigmatizing statement. schizophrenics are no more of a danger to others than the general population. It is because society treats them like shit and so they take drugs to cope that makes them violent. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852683/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852683/ "Patients with schizophrenia without comorbid substance abuse have only a slight increased risk of violent crime compared with the general population, suggesting that substance abuse plays a mediating role."
Pixie_Dust 3y ago
My Schizophrenic friend tells me the difference between schizophrenics and normal people is that normal people can hear their own thoughts whilst schizophrenics can hear other peoples. Serious point, maybe schizophrenic symptoms are cause by a disruption in REM sleep. As in the suffers are experiencing a waking dream. Some time back they did an experiement on students and kept them awake for days-and-nights on end. Eventually they couldn't tell the difference between the dreaming and the real world.
- kayodelycaon 3y ago
  Many things can cause psychosis, so it's difficult to draw cause and effect out of the data. I've experienced severe psychosis. For me, it was a merging of reality and imagination. I always knew what was real, but my brain couldn't filter and ignore the unreal. I would act as if imagination was reality though I knew it wasn't. Several people I've talked to have said similar things. I think of dreams as the result of rebooting the brain mid-defrag. It's chaotic in some way. My experiences with psychosis was far too structured and self-consistent to be a dream. My theory is there is an active component to psychosis that doesn't fit in with REM sleep as a cause.
- wheelerof4te 3y ago
  That's because their brains were rebooting when their body senses low activity. Kind of like sleep function on laptops. Otherwise, the brain cells would "overheat".
  - cududa 3y ago
    This analogy is wrong on so many levels. Human sleep would be more aptly related to garbage collection and indexing - neither of which occur when a laptop sleeps. When a computer overheats it throttles performance and sometimes shuts down.
    - wheelerof4te 3y ago
      When a brain overheats, you can easily lose consciousness and be forced to sleep. Wheather you like it or not. So, not that wrong as you might think.
calibas 3y ago
I have a theory. Antipsychotic medications just need to make the person more "manageable" to be considered effective. It doesn't need to eliminate the psychosis directly, it could just make the person more sedated, and it would appear to be "working" properly.
- throw18376 3y ago
  this is unfortunately part of how they are used, especially in inpatient settings with way too high doses. but also, if you've had a conversation with someone in active psychosis, vs. on the right dose of medication, there is a really incredible distinction in the clarity of their thinking and speaking -- night and day sometimes. so the drugs do work at genuinely treating some of the problems. and good psychiatrists do look carefully for this kind of improvement.
- cududa 3y ago
  That's not really your own theory, that's like, the specific goal of psychiatric treatment? You can't "cure" schizophrenia or bipolar, the goal is to manage it. My dad developed severe mental illness later in life, destroyed his life, and never found a regiment that worked for him before his death (undiagnosed congenital heart condition is what ended up getting him). I think anyone who has schizophrenia or bipolar (and their loved ones), would happily take medically "managed" psychosis over the hell of unmanaged psychosis
  - calibas 3y ago
    You're mixing up managing a disease and managing a person. Managing (treating) mental illness is not simply about making the person more manageable for others. There's drugs that reduce or eliminate hallucinations for many schizophrenics, so it's something you can treat (except in unfortunate situations like your dad or my uncle). There's a big difference between a medication that actually removes the symptoms over one that sedates a person, they're not the same and one is obviously preferable. There hasn't been enough concern about how the drugs work, or why they often cause serious side-effects like tardive dyskinesia. It's simply enough that the person becomes manageable for others. These drugs have been around for a long time and only now is someone investigating deeply into how they actually work.
at_a_remove 3y ago
Schizophrenia is a strange illness. We've had two successes (by some metrics) in psychiatric treatments because the science aimed at schizophrenia but hit something else: lithium and electroshock.

146 points by thedday 3y ago

The entire paradigm for treating schizophrenia and other chronic mental states is flawed. Mental distress/disorder cannot be treated properly because of the strong for-profit motive (unrestricted greed) that these privately-owned (sometimes publicly traded) mental hospitals and pharmaceutical companies have. Mental hospitals are effectively a prison. Locked doors, removal of rights once committed, coercive and sometimes forced treatment and restraints, being told that you have a lifelong disease (with no measurable physical damage -- fMRI scans are not indicative of damage) that needs drugs for the rest of your life, and getting billed an exorbitant amount - to name a few things that are wrong. If your rights are violated and you are declared incompetent (which is pretty common if you are unstable or in crisis), it's an uphill battle in special courts called Mental Health Courts. It's difficult to get a second opinion from a third-party psychiatrist, or to contest treatment orders (such as mandatory intramuscular antipsychotic injections or ECT which respectively have a very potent and long-term effects). The conversation needs to be shifted towards the Soteria House paradigm. This article sums this model of care pretty well: https://www.madinamerica.com/2019/09/soteria-house-heal/ https://www.madinamerica.com/2019/09/soteria-house-heal/ They have very impressive results, particularly in regards to schizophrenic and psychotic patients, and do not use life-long tranquilizer prescriptions to achieve their results. It needs more study, it needs more implementation, but the core of the model is that it builds a supportive community around vulnerable people -- instead of caging and viciously profiting off of these people. I spoke on this matter in the past, and you can read my thoughts here: https://news.ycombinator.com/item?id=34029719 https://news.ycombinator.com/item?id=34029719

leon_theremin 3y ago

[flagged]

canistilkehese3 3y ago

It's important to keep in context that none of hepsteens clients were persecuted or even publically named, and the people connected to them take a percentage of every profit you work to generate. Don't call them out on that though, these sedatives will fuck you up.

A_D_E_P_T 3y ago

Situation normal. Consider the discovery of valproic acid: "Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder." To this day, nobody knows exactly how it works, apart from the fact that it hits more than a few targets. (And it's a particularly potent inhibitor of the epigenetic modulator histone deacetylase.) Apart from a subset of very clear-cut cases -- steroid hormones, peptide hormones, and certain aggressive chemotherapeutic drugs -- there's no clear model for most small molecule drugs. Even really mundane ones like metformin and paracetemol are very imperfectly understood.

aatd86 3y ago
Normal might be a strong word. It messes with the brain which is the core. Goes to show a lot of clinical medecine is about short-term relief and not necessarily about real health. If you really look at it with unbiased eyes, between elective surgeries and what not, it's not really about curing any true dysfunction sometimes. Perhaps too many times. We just go with the flow but, heck, MDs are not even necessarily healthier than you, some even smoke to this day! Go figure...
- crooked-v 3y ago
  You've gone off on an unrelated tangent here. "Situation normal" in this case means that, as with lots of drugs, we only poorly understand the mechanism by which they actually work, and that new discoveries can completely change our understanding of how to use and improve on them.
  - aatd86 3y ago

yuck39 3y ago

Link to the actual paper: https://www.nature.com/articles/s41593-023-01390-9 https://www.nature.com/articles/s41593-023-01390-9

gvb 3y ago

https://archive.ph/sZerh https://archive.ph/sZerh

whats_a_quasar 3y ago

The brain is really complicated, and all psychiatric medications affect multiple receptors and subsystems. Framing this study as "antipsychotics were off target" is an editorial choice. The title could just as easily have been "Improved understanding of antipsychotic action means we may be able to design better antipsychotics." Edit: It also ought to be noted that the study was on mice that had been given amphetamines to mimic psychosis. Which is interesting and good science, but seems far from enough evidence for the press to write stories with headlines like "Everyone Was Wrong About Antipsychotics" or "Schizophrenia Drugs May Have Been Off Target For Decades, Study Finds." This sort of internet story bothers me because I've spent time around schizophrenics who are recovering from a psychotic episode. Schizophrenia can get really, really bad, in a way that I don't think most people who haven't had contact with the psychiatric medical system understand. Antipsychotics have awful side effects, but for many people the alternative is uncontrolled psychosis, which can be vastly worse. There's a decent chunk of people who inherently and vocally dislike psychiatric medication, and these media stories are in that tradition. But the only people who ought to be involved in the decision about using antipsychotics are the patient, their family, and their medical providers. Writing headlines that are too broad for the evidence that supports them does not help improve the lives of people with schizophrenia.

Lutger 3y ago
This media story isn't 'in the tradition' of vocally disliking psychiatric medication. You could twist the headline to be, possibly. Have you read the article itself? Its the complete opposite. The headline is a bit attention grabby perhaps (and of course, that is what a headline must do), but I wouldn't even call it clickbait. It is even fairly accurate. Yes, they were likely off target with the specific neuroreceptors, no that doesn't mean the medication didn't work and of course, this is a positive development for designing better medication. This is classic storytelling, draw the reader in with some conflict and save the resolution for the end. We need to be able to discuss negatives and limitations associated with psychiatric medication in an honest and nuanced way. They often don't work well enough, there are costs associated and just giving somebody a pill and be done with it is hopelessly inadequate to the point of negligence. As someone who did experience uncontrolled psychosis myself, let me tell you the absolute taboo of discussing these matters made me way more uncomfortable than the side effects. Furthermore, psychiatry made me feel like a diseased animal at times, not to be taken very seriously and just put on drugs for life to be on the safe side. In hindsight I do appreciate how difficult that line of work is, doesn't change my experience. I am not against medication really, actually I think they are a must-have. I just think most anti-medication people are not really rallying against the side effects or at least not initially, but grew opposition out of bad experiences with treatment that focuses only on medication and was just very inadequate. Medication is what represents that. Additionally, medication can come to represent your loss of sanity and with that, you fundamental not-belonging to the group of 'normal people'. Thus the desire to not be on meds 'for life'. Haven't spoken to a single therapist or psychiatrist who made me feel that was a legitimate desire and who understood that. Maybe things have changed, this was a long time ago. To deal with the resentment against meds, I think it is way more effective to address those concerns directly and without fear, rather than putting down everything that might be interpreted as negative about medication. Like you say, without experience yourself, you have no idea how bad psychosis can get. It is a really complex thing and you will need much, much more than pills. And not only for the psychotic episodes, because these experiences tear at your identity as a human being. It isn't over when the psychosis is over.

rybosworld 3y ago

It's amazing how far the medical world has come in treating ailments of the body, but we've made comparatively little headway in ailments of the brain.

toasted-subs 3y ago
There's a million reasons why. And I can't get into it without being called a quack. And yes, washing hands is common practice now.
whatscooking 3y ago
We haven’t gotten far at all. We treat symptoms, not diseases
FollowingTheDao 3y ago
Last I checked my brain was part of my body. And that is why so little headway has been made, people keep thinking the body and brain act independently of each other.
pixl97 3y ago
If instead of saying brain you say "The most complicated structure found in the known universe so far" it starts to make a little more sense on the enormity of the problem at hand. Most organs are composed of one or only a few types of cells and their particular arrangement doesn't matter that much. For example swapping kidneys between people doesn't change who they are (mostly, smaller edge conditions apply here). But we can't swap brains because the brain encodes your 'youness'.
- BurningFrog 3y ago
  You can also think of "the brain" as a collection of 10-20 separate organs, rather than one super complex one.
  - pixl97 3y ago
    While true, the complexity of each organelle in the brain is still much higher than that of the typical organ elsewhere in the body. That and there is a high degree of connectivity and feedback between components where the API is completely and totally undocumented. It's not that you don't know what the known API calls do, you don't have any clue on how many API calls there even are. Accidently emulating one of these calls when attempting to trigger a different behavior can lead to wildly unexpected outcomes.

merricksb 3y ago

Same study discussed previously: https://news.ycombinator.com/item?id=37057135 https://news.ycombinator.com/item?id=37057135 (50 points/3 days ago/51 comments)

Aurornis 3y ago

The study used a mouse model where amphetamine is used to simulate schizophrenia. Obviously, it's not guaranteed to map to real humans having real schizophrenia. That doesn't mean it's a useless result, but everyone should remember that research is an accumulation of decades of many little pieces of information. This is another clue, not a "nail in the coffin" of old theories. The ultimate evaluation of medication is how well it actually performs in studies. If someone can develop a new medication that is more selective for D1 and show that it performs better and/or has fewer side effects then this would be a great result. However, don't get too excited. The pharmaceutical industry is often 10 steps ahead of public findings like this. A selective D1/D5 antagonist with negligible D2 affinity has already been trialed for schizophrenia without good results: https://en.wikipedia.org/wiki/Ecopipam https://en.wikipedia.org/wiki/Ecopipam Many of the most prescribed schizophrenia medications already have significant D1 affinity, too, so it's not really correct to say that we're "off target" These findings tend to be very aggravating to computer scientists who are familiar with systems that (mostly) obey clear-cut rules and can examined in extremely fine detail with enough equipment and motivation. Neuroscience is not so simple, but that doesn't mean it's all wrong. Each finding is one more piece of the puzzle.

fragmede 3y ago
While everyone should be keenly aware the limitations of taking experimental results in mice and extrapolating to humans (aka, they often don't), doesn't that mean what we really have, is a bunch of well tested medication for meth addicts? Which; if there was a way to get meth addicts off meth, would be a boon?
- monknomo 3y ago
  It's not for addiction, but yes, if someone takes enough meth to induce psychosis, antipsychotics will reduce the psychosis.
- edgyquant 3y ago
  Not necessarily addicts. You don’t have to be addicted to achieve psychosis you just need to take a certain amount. For me this amount is pretty small, I was prescribed adderal for awhile and even 20mg was enough to induce serious paranoia and the occasional hallucination

justsomeguyhere 3y ago

So I've tried half a dozen antipsychotics, here are my 2 cents: The only things those drugs did to me were making me comatose, poop my pants, sleepy, dumb and hungry. You can't be declared psychotic or paranoid, when the only thing you can do is sleep, drool, poop yourself, and make 3 words sentences, so lazy doctors think these drugs work. But they don't, there was zero change in my beliefs, fears, anxieties, I was the exact same person, only slower, dumber, and sleepier. And at some point, when you're exhausted from being a zombie, you end just lying to your doc and pretending everything is fine, even when you believe doctors should always know the truth, because it's the only way to stop yourself from staying a brain dead zombie for life and causing irreversible damage.

winocm 3y ago
Concur. Those medications ruined my life.
tredre3 3y ago
I recognize myself very much in your words. I've also tried everything and it does not change my beliefs, fears, crippling anxiety one bit. Let alone improve my mood. Thankfully does help with mania. But the side effects are pretty bad and the doctors I've met tend to dismiss them, especially the more esoteric ones. So I have to lie to doctors to steer them towards the care I really need. I would prefer not to lie. I tried not to lie. But when you tell them you want to quit or go as needed, they gently suggest committing you or lose interest in you. They see you as a toy to experiment on. It's impossible to be treated like an adult. It's infuriating.
thrw238592 3y ago
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- kayodelycaon 3y ago
  You do need to be careful adding vitamins and supplements without medical guidance. For example, magnesium can interact with medications. I can't actually take it because there isn't a safe, reliable time in my daily medication schedule for it.

winrid 3y ago

One of the more popular Schizophrenia drugs also cause diabetes :(

psychphysic 3y ago
One?! It's pretty much all second generation... Metabolic side effects could probably be used to define SGA!
Pixie_Dust 3y ago
> One of the more popular Schizophrenia drugs also cause diabetes :( Not to mention, weight gain leading to type two diabetes, thyroid problems leading to fluid retention in the legs and memory loss. Not much of a cure :(

robinduckett 3y ago

I know someone who has diagnosised but untreated schizophrenia. She was admitted to the hospital after she started having thyroid problems and they also administered schizophrenia medication while she was in. The change in her behaviour was positive and dramatic and allowed her to start accepting help after being scared that men in white coats would take her away if she ever let on about her illness to anyone. Now she has been out of hospital for a while, unmedicated again and back to her old behaviour including talking to people who aren’t there and having bad episodes. Maybe some medications are off the mark but whatever they used for her absolutely worked. I realise a sample size of one anecdotal piece of evidence is hardly scientific, but I’m getting rather tired of the constant mouse model studies, with barely related parameters. I wish there was a better way to do medical research, in actual human beings. Unfortunately it seems historically that actual human medical research is mired in the suffering of the (generally unwilling) participants.

P_I_Staker 3y ago
[flagged]
- ChrisClark 3y ago
  > Now she has been out of hospital for a while, unmedicated You're wrong, it obviously worked. Might want to check into your own beliefs about why the doctors are trying to sap all your bodily fluids.
  - P_I_Staker 3y ago
    I don't think you read my comment. This issue is actually highly contentious. If a remedy consistently has poor results, it's a bad remedy. Simply saying "it works for the ones that are righteous" is absurd. If you break it down that's generally what people are saying, but usually use words like lazy, stupid, crazy, addict, etc. If most patients can't or won't follow a treatment maybe it doesn't work so well. > Might want to check into your own beliefs about why the doctors are trying to sap all your bodily fluids. This is very insulting, and demeaning, not to mention untrue. At no point did I imply doctors are trying to sap me of my "bodily fluids". I've never believed anything close to that. A leach sucks body fluid, so I guess it's a bit like that, but metaphoric. You seemed to care about your friend. I don't see the point in blatant bigotry towards mental illness.

psychphysic 3y ago

The pharmacodynamics of antipsychotics is such a rich topic, yet this article is so crap! Surprised no mention of pimavanserin (which doesn't act on dopamine useful in those with Parkinson's and psychosis) and that L-dopa can reliably induce psychosis (used on Parkinson's).

tcj_phx 3y ago

Strictly speaking, psychosis is more strongly related to excess serotonin, 'the molecule of stress and inflammation'. Doctors sometimes recognize 'Serotonin Syndrome' in their ER patients: "too much serotonin causes signs and symptoms that can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever and seizures)." Usually the Serotonin Syndrome is caused by a combination of prescriptions, or street drugs. https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758 https://www.mayoclinic.org/diseases-conditions/serotonin-syn... All the effective anti-psychotics seem to have anti-serotonin properties, in addition to their anti-dopamine effects. For example: "there are also recent studies that 'stumbled upon' the 'shocking' evidence that anti-dopamine drugs commonly used for treating schizophrenia such as haloperidol are actually potent serotonin antagonists as well." - http://haidut.me/?p=1297 http://haidut.me/?p=1297 One of you quoted my essay Cargo Cult Psychiatry in a comment on Sunday, on a submission of Feynman's Cargo Cult Science. I responded, then thought to submit my link to the original at Mad In America again: https://news.ycombinator.com/item?id=37110874 https://news.ycombinator.com/item?id=37110874 This paragraph from that comment is essential for helping anyone diagnosed with the label of "schizophrenia": "The good news from the mental health world is that Chris Palmer, M.D. published Brain Energy [0] last year. I haven't read more than excerpts from google books [1]. My understanding is Dr. Palmer was a conventional palliative psychiatrist, then he had a patient whose schizophrenia improved on a ketogenic diet. The patient was able to discontinue antipsychotics: Dr. Palmer's mind was blown. Then he discovered the 70+ years of research establishing that mental health conditions are metabolic problems that can be successfully treated with pro-metabolic therapies. Perhaps the most bold and disruptive aspect of Brain Energy is understanding precisely how and why medications that harm metabolism might reduce mental health symptoms. The long-term consequences are of great concern and require the urgent attention of the psychiatric community. -Chris Palmer, MD - https://twitter.com/ChrisPalmerMD/status/1687850270602981376 https://twitter.com/ChrisPalmerMD/status/1687850270602981376 [...] [0] https://brainenergy.com/ https://brainenergy.com/ / [1] https://books.google.com/books?id=FoxlEAAAQBAJ&pg=PT233&dq=B https://books.google.com/books?id=FoxlEAAAQBAJ&pg=PT233&dq=B "

psychphysic 3y ago
pimavanserin case in point

11235813213455 3y ago

I was diagnosed with schizophrenia, given some strong antipsychotics, it was a disaster I could barely talk or hand-write properly, gained 15kg. Fortunately I didn't listen the advices and stopped after 4 months, my therapy now is just walking, running, cycling, outdoor, trees, vegetable, minimalism

tredre3 3y ago
> Fortunately I didn't listen the advices and stopped after 4 months, my therapy now is just walking, running, cycling, outdoor, trees, vegetable, minimalism Over-medication is a big problem, but you have to recognize that you are extremely lucky to be able to function without it. Not everybody can. I couldn't. I share your experience regarding side effects, it would likely kill my career. Thankfully anti-psychotics work quickly, unlike antidepressants. As long as I have the discipline to recognize the signs, I can medicate mostly as needed. But this, again, is a privileged situation. More severe cases can't risk that "as needed" treatment.
- 11235813213455 3y ago
  Right,my case is light (I've always had a job, at least between major burnouts), and the injections were way too big for my weight. It was efficient as I was calm at that moment, I started reading books again, but I lost all my passion for things, my brain was like mostly turned off, that's why I preferred returning to the previous state and finding other solutions
m_0x 3y ago
Pardon my ignorance and prejudice, but how are you not a danger to the people that surround you? Or is schizophrenia a spectrum very much alike as autism?
- FollowingTheDao 3y ago
  hey, that was a pretty, uh, stigmatizing statement. schizophrenics are no more of a danger to others than the general population. It is because society treats them like shit and so they take drugs to cope that makes them violent. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852683/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852683/ "Patients with schizophrenia without comorbid substance abuse have only a slight increased risk of violent crime compared with the general population, suggesting that substance abuse plays a mediating role."

Pixie_Dust 3y ago

My Schizophrenic friend tells me the difference between schizophrenics and normal people is that normal people can hear their own thoughts whilst schizophrenics can hear other peoples. Serious point, maybe schizophrenic symptoms are cause by a disruption in REM sleep. As in the suffers are experiencing a waking dream. Some time back they did an experiement on students and kept them awake for days-and-nights on end. Eventually they couldn't tell the difference between the dreaming and the real world.

kayodelycaon 3y ago
Many things can cause psychosis, so it's difficult to draw cause and effect out of the data. I've experienced severe psychosis. For me, it was a merging of reality and imagination. I always knew what was real, but my brain couldn't filter and ignore the unreal. I would act as if imagination was reality though I knew it wasn't. Several people I've talked to have said similar things. I think of dreams as the result of rebooting the brain mid-defrag. It's chaotic in some way. My experiences with psychosis was far too structured and self-consistent to be a dream. My theory is there is an active component to psychosis that doesn't fit in with REM sleep as a cause.
wheelerof4te 3y ago
That's because their brains were rebooting when their body senses low activity. Kind of like sleep function on laptops. Otherwise, the brain cells would "overheat".
- cududa 3y ago
  This analogy is wrong on so many levels. Human sleep would be more aptly related to garbage collection and indexing - neither of which occur when a laptop sleeps. When a computer overheats it throttles performance and sometimes shuts down.
  - wheelerof4te 3y ago
    When a brain overheats, you can easily lose consciousness and be forced to sleep. Wheather you like it or not. So, not that wrong as you might think.

calibas 3y ago

I have a theory. Antipsychotic medications just need to make the person more "manageable" to be considered effective. It doesn't need to eliminate the psychosis directly, it could just make the person more sedated, and it would appear to be "working" properly.

throw18376 3y ago
this is unfortunately part of how they are used, especially in inpatient settings with way too high doses. but also, if you've had a conversation with someone in active psychosis, vs. on the right dose of medication, there is a really incredible distinction in the clarity of their thinking and speaking -- night and day sometimes. so the drugs do work at genuinely treating some of the problems. and good psychiatrists do look carefully for this kind of improvement.
cududa 3y ago
That's not really your own theory, that's like, the specific goal of psychiatric treatment? You can't "cure" schizophrenia or bipolar, the goal is to manage it. My dad developed severe mental illness later in life, destroyed his life, and never found a regiment that worked for him before his death (undiagnosed congenital heart condition is what ended up getting him). I think anyone who has schizophrenia or bipolar (and their loved ones), would happily take medically "managed" psychosis over the hell of unmanaged psychosis
- calibas 3y ago
  You're mixing up managing a disease and managing a person. Managing (treating) mental illness is not simply about making the person more manageable for others. There's drugs that reduce or eliminate hallucinations for many schizophrenics, so it's something you can treat (except in unfortunate situations like your dad or my uncle). There's a big difference between a medication that actually removes the symptoms over one that sedates a person, they're not the same and one is obviously preferable. There hasn't been enough concern about how the drugs work, or why they often cause serious side-effects like tardive dyskinesia. It's simply enough that the person becomes manageable for others. These drugs have been around for a long time and only now is someone investigating deeply into how they actually work.

at_a_remove 3y ago

Schizophrenia is a strange illness. We've had two successes (by some metrics) in psychiatric treatments because the science aimed at schizophrenia but hit something else: lithium and electroshock.