hckrnws

https://archive.is/BYzWs

I lost a good friend to this. Hope it helps other people.

The meds helped him but he didn't like the side effects so he stopped taking them. Went in and out of homelessness. In the end he thought he had superpowers and could fly. He could fly, but he could not land. It eventually took him.

Oh man, I'm probably half schizophrenic, tried some antipsychotics at some point and had same reaction, and recently started to spend most my time outside (sleeping too), I found a nice spot. Fortunately I still have my remote developer job, and try to remain stable but I'm over sensitive and in the long run I can't sleep in my apartment (noise, smells - cigarette, here in France, it's horrible, maybe WIFI waves too). But isolation tends to makes me a bit more tolerant to people, I love birds and any really natural living being though

I'm not a professional, and I'm not diagnosing, but I am diagnosed autistic and I share some of what you're talking about here.

I'm sensitive to noise, smells, lights and vibrations (living next to a very busy road, I can feel almost every large non-electric vehicle go by -- makes working from home hard at points).

Worth reading into if you have the energy. I do know folks who are diagnosed with schizophrenia and they seem to have an underlying component of some neurodivergence (arguably schizophrenia should also be considered neurodivergence) and went through an extreme burnout/traumatic event.

Hope you're able to get some peace!

I moved twice in the last few years. Immediately after moving I was completely unable to sleep. Too bright. Too loud. What are these noises? What is that vibration? For me, it fades after a few weeks. The train can be rumbling by with the horn going and I'll sleep right through it now. I think maybe for some, that filter never builds up. Not sure how to articulate it but it does seem a significant component of both autism and schizophrenia (which in some ways seem to be almost opposites) is a difficulty in developing that sort of filtering-out of the constant sensory bombardment we're all under.

Acclimitisation can be hard. In some cases I can put things to the back of my mine, but often it's just hard or not possible.

Certainly in my experience and from talking to others who identify or have been diagnosed similarly, in the majority of cases you don't get used to certain things. You can't acclimitise and that's why a load of people who are autistic aren't employed.

I might seem okay in the office, but what isn't seen is my complete inability to function at home if there have been too many inputs and distractions. Lucky I can work from home a couple of times a week and my hours are flexible in that I can start earlier so not to travel into the city when it's busy -- busses are quiet at 05:00/06:00 thankfully!

Having a small office I share with a few people helps. My last place went all in on the open-planned office and it was hell. I can't see how anyone is getting much work done in environments like that, haha.

Schizophrenia is certainly neurodivergence, as far as I know. I've often seen it depicted that autism and schizophrenia are roughly on opposite sides of neurotypical:

- Autism can make one prone to detail-oriented thinking, focusing on small details, requiring logical connections to understand and apply ideas. Constraints are well understood and considered. This can result in stuff like OCD.

- Schizophrenia can make one prone to disconnected thinking, focusing on big pictures, fitting together ideas that may seem entirely unrelated. Even constraints that seem obvious may be completely ignored. This can result in stuff like conspiracy theories and convoluted delusions. Delusions happen because beliefs may not be constrained by what's actually realistic, the big picture could be more prominent.

I don't know how true this analogy is, but it certainly seems interesting to consider.

Very insteresting, my father thinks I'm autistic, while some psychiatrist concluded for "Hebephrenic schizophrenia". In my developer work I tend to rush things a bit, maybe because I don't know how long I'll feel in peace, but if I can really find peace, then I deeply focus like an autist. Also I'm not associal (except the fact I don't like cigarette, so I'll avoid crowd due to that unfortunatly) I usually engage conversations with anyone, helps breaking my loneliness, and that's not really a trait of autists I believe (who are more shy/introvert/associal no?)

> I usually engage conversations with anyone, helps breaking my loneliness, and that's not really a trait of autists I believe (who are more shy/introvert/associal no?)

I think 'autistics' is a better term here; 'autists' can make... not the best impression.

Anyway: no, autistics aren't necessarily more shy/introverted/asocial. I'm autistic and I'm definitely not that way; I usually try to connect to as many people as I can and I have to speak to people essentially every day or else I get extremely lonely/depressed. Part of this is probably due to ADHD and possibly also B(orderline)PD, but it's also because that's just the way I am.

It´s a spectrum https://neuroclastic.com/its-a-spectrum-doesnt-mean-what-you...

> arguably schizophrenia should also be considered neurodivergence

Isn't it? My understanding of the word is "anyone who experiences the world differently from the social 'normal'", which would certainly include schizophrenia and other kinds of mental disorders.

I'm with you, I thought neurodivergent included any folks whose brain chemistry was different than the 'regular' baseline. Bipolar, schizophrenic, etc.

In the genderified xitter space "neurodivergence" has been hijacked to mean adhd and autism only.

I cant wait for the TikTokers to find out about Schicofrenia where they can actually think they are god!!

> arguably schizophrenia should also be considered neurodivergence

Nope never!

I have experience with schizophrenia and it can never be confused with anything else. The person with it is devoid of reality and does not know they are sick. They resist treatment and sometimes would rather go homeless, stop eating or taking care of themselves, in order to avoid treatment. They pull down everyone in their lives trying to help them, and it really takes a toll on family and relationships.

I couldn't agree more with you. I've got a brother who's been diagnosed with schizophrenia. He's in denial and it's a constant worry that he will stop taking his meds again. It's a brutal, life-destroying illness if it's not managed. His lows are truly soul-destroying to witness.

Just out of curiosity (no obligation to respond): how long have you been experiencing these difficulties? Have you always been sensitive to these things?

I'm 39 now, since 22-24 so 15+ years, it started at the end of studies, I started to stop spending money (except appt. rent), OCD things appeared, I manage to keep stable jobs and after years I started eating better, fueling better the brain, most OCD troubles disappeared, but I feel like I changed myself to someone more sensitive, more wild in some way. in the long run I can't handle a "normal life", sit down in a closed air-conditioned place, eat industrial food, tolerate cigarette smokers around, noisy motorbikes, and all forms of pollutions. I started to also try to avoid polluting as much as possible, by respect for nature, which is my real efficient treatment I think

I would move outside of the city/town, on a very small but independent house far from others. A quiet and beautiful natural place. Now internet is everywhere and it’s possible to work from nice places.

The problem is if you need medical care, there aren't great options in rural areas.

Source: the closest hospital to me is 30 minutes and it sucks out loud for anything but basic injuries.

May be true, but if there are no other pathologies that require frequent visit to the hospital, and the quiet living might help the mental side of things, why not? Maybe giving it a go for a while at first.

Maybe it’s just me, I only once in almost 40 years required urgent medical attention and would have survived without.. so I don’t understand the worry about not having an hospital close to home.

Thanks yes that's my plan and hope. I don't need much healthcare, except maybe teeth (that got a bit damaged when I was too underweight), not something frequent

Good luck. I really mean that.

Rural living definitely is relaxing and helps you connect with nature. But the isolation can be difficult. Hit me up if you want tips on how to cope. I am not schizophrenic, but I do have Tourettic OCD which makes it hard to 'fit' into society at large.

I do want to stress, if you have untreated mental illness, rural life is not a cure. It can make it worse.

>maybe WIFI waves too

Certified nutcase comment lmao, WIFI waves do not do anything are you gonna buy some shugnite rocks too like the two timer, also smoke smell, move then or move out of city. Im mentally ill too but its mild autism, adhd (takes me all day to watch a 2h movie I pause adn pause and pauise and pause and pause and pause) and depression (I recently cleaned my fridge from 4 year old rotting food) but astleast I sleep inside.

I don't know for WIFI, but I really receive 4 with 5/5 connectivity, and more than 30 in total from my apartment, it's crowded, and that's a bit silly that everyone installs their own box. I don't know exactly where it comes from, but even when it's calm and breathable, I don't feel especially good in my apartment, the difference with outside is incredible, so I'm trying to sleep, eat & work outside. I go back at my appt so recharge batteries, water bottles and food

It's not the Wi-Fi.

>I don't feel especially good in my apartment, the difference with outside is incredible

You have a mold issue in your apartment or some other problem like that then.

A little empathy goes a long way man. I would really consider why you feel the need to respond to people who are clearly struggling like this

Im just a lil sicko xd

No really I probably have some light autism, when I see someone being wrong online I cannot help myself.

Having wifi allergy or electric allergy is a mental illness and symptom of shcizo. No need to sugar coat this man he is an adult.

There are plenty of other hugboxes online.

Being downvoted for tone, I guess, but the "remote influencing via waves" is _the_ classic delusion common to a lot of psychotic disorders.

The poster needs to seek actual help.

> The meds helped him but he didn't like the side effects so he stopped taking them.

This is frustrating to me as a long time psych med user. If the meds have intolerable side effects then the meds do not help. Period. I do better off my meds than anything they ever tried to give me.

The system failed your friend. Not his ability to tolerate these horrible side effects.

IF we actually cared about human life we would have done much more to help your friend, but we did not. We care about human life up to the point it starts diminishing our comfort, and I am afraid we are valuing our comfort more and more than we care about others who are suffering in the last thirty years.

> The meds helped him but he didn't like the side effects so he stopped taking them.

They, their family, or guardian should have consulted their psychiatrist to tune the meds for less side effects or to switch them. That is what psychiatrists are there for.

Especially for schizophrenics, they should never have the option to get off meds, in fact there should be a long acting backup med to go with the normal treatment in case the patient were to skip a dose.

Those with experience with schizophrenia know this is the hardest part of dealing with this mental illness - getting the patient into treatment and onto meds. Sure it is easy to maintain meds, but on boarding is the biggest challenge - that once it is setup, working, and bringing the patient back to reality it needs to be maintained, otherwise the patient and family have another long, uphill battle getting the patient back under treatment.

> they should never have the option to get off meds

(I have Schizoaffective Disorder)

The meds do not work and they have horrible and even deadly side effects. To say I should never be allowed to stop them denies me of my agency and would force me to endure a life of misery. I am no longer on medications and better than I have ever been. I am rare. Even psychiatrists do not like this idea.

We could open up psychiatric institutions again like they were when my mother was in one. It was great for her. Now we have these prisons they call psychiatric hospitals run by fro profit companies. (Just google Holly Hill Hospital in Raleigh, NC for an example.)

What we need is better research that is not dominated by funding from Corporations. All funding should come from the Government.

> they.. should have

Believe me, "they" tried. Just finding him was hard and he moved to a remote location. Gave away all of his possessions, including cell phone. Lived in a temperate climate where it was easy to get "lost" in the vegetation and live off the land.

It appears there is more suffering and misery out there than any single concerted effort could solve.

I’m in NYC and just yesterday saw a homeless guy pick up a used needle from the street and check to see if it had any drugs left in it. The story that led him that state, and where that story goes from here, multiplied by thousands of people in a big city alone…it’s hard to imagine solving that.

Same story here, more or less. Freshman roommate.

It's probably a common story.

This reads like a happy clappy advertisement.

It is often not the common side effects: "gain weight, fall asleep and experience involuntary muscle jerking" that cause people to stop taking meds. It is that their brain feels different, not like how it should be.

Now involuntary muscle jerking has a high stigma. It can, in the worst cases be highly visible. The new drugs seem to stop this drawback and instead introduces vomiting. That would be even worse.

The worst part of the article though is the frequent reference to homeless people. and that seems to be written by someone who has no idea of the realities.

A majority of homeless people do not have access to even basic healthcare. There are different reasons for this, but it is true of the majority. You dont have a look that closely to see open wounds, some infected, esp on feet and legs. These are basic healthcare concerns. Probably they have several other conditions that require treatment, and deficiencies due to a lack of food period, and certain lack of food that is nutritious and healthy.

Are the doctors just going to walk up and down the lines of homeless giving out bottles of pills and hope the world will change?

These types of drugs should always be closely monitored by a psychiatrist. Which is made nearly impossible with homeless people. (not to mention the cost. It could have high co-pays but I hope there are programs that can mitigate this.

The only way to do this is to give the person a place to live. Ensure the person has healthy and decent food. This will require time and treatment so build up a new sense of safety.

Once achieved treatment for schizophrenia could start with the drug and be closely monitored by professionals.

None of the drugs to treat mental health issues will work on all, And some people will have strong side effects.

My read on the one reference to homelessness in the article was that a life-changing medication that can help with a disease like schizophrenia can prevent homelessness in the first place.

I have a close family member that had a psychotic episode during the pandemic. They were hospitalized but were eventually able to get effective treatment and medication and now live a mostly normal life.

Had they not had the support to get proper medication, I have a hard time seeing how they wouldn’t end up homeless.

After seeing how much they are going to charge for it, I am not sure if it will not cause more homelessness.

Not saying it is or isn't overpriced, but 20k/year is actually a good price for something that can avoid homelessness. Just the cost of extra medical care and/or jail, let alone social services and lost productivity, is worth it.

$20k per year for a brand new drug that went through 15 years of development is peanuts. Welcome to healthcare in the country that leads the world in pharma research, for good and for ill.

Napkin mathing here since available data isn't great, but the US definitely doesn't lead the world in healthcare R&D spending relative to our size. We're spending something like 0.22% of GDP on healthcare R&D, putting us at about #7 globally. In comparison, Denmark spends 0.93% of GDP on healthcare R&D. And that list is missing data from other countries that probably rank above us, like Cuba.

Sources: https://www.oecd-ilibrary.org/docserver/sti_scoreboard-2009-... https://www.who.int/observatories/global-observatory-on-heal...

> $20k per year for a brand new drug

The thing is you don't even need this new drug, from the article "Risperdal and Zyprexa" are very effective antipsychotics. Even more effective when combined with a long acting to prevent backslide from missed does.

Who cares about the TD, tremors, etc. when that patient can rejoin society? Really what needs to change is reopen US mental hospitals to get these patients treatment and end the stigma around mentally illness.

That isn't how that works. That isn't how any of this works.

21% [1] of homeless have a serious mental illness that predates their living situation, of which an even smaller chunk is schizophrenia. The major reasons for homelessness are predominantly financial (also [1]). We think that the sequence of events is mental illness/drugs → homelessness → poverty, but the true sequence is an averse financial event + lack of support → homelessness → mental illness (as a result of the homelessness) → drugs to cope.

We saw the most pronounced examples of this in Houston's homeless program, which has a 90% success rate by providing housing first [2]. For many, having a safe home is the only resource needed to get clean.

Homelessness is torture. Anyone in that situation would turn to drugs to cope. Demonizing the drugs is flying straight over the cause of the drugs themselves. If you want to fix homelessness, give homeless people homes.

[1]: https://www.samhsa.gov/blog/addressing-social-determinants-h...

[2]: https://www.thewayhomehouston.org/

Do you have a source that suggests that mental illness/drugs do not contribute to becoming homeless?

> 21% [1] of homeless have a serious mental illness that predates their living situation

This seems to suggest that mental illness does lead to homelessness. I would agree that financial strain is a major cause of homeless, but it seems likely that this is because it leads to other behaviors that then lead to homelessness. And those behaviors are probably not exclusively caused by financial strain.

Additionally, from the conclusion of your first link (my italics added for emphasis):

> SAMHSA utilizes its national surveys and grantee data to create effective programs and services to prevent and end homelessness among people with mental and substance use disorders.

Secondly, I agree that housing is an important first step for fixing homelessness because it seems like a precondition for stability.

But this:

> For many, having a safe home is the only resource needed to get clean.

seems misguided to me. "Housing First" != exclusively housing. From your second link:

> we move people into permanent housing as quickly as possible and then provide them with supportive services (like case management, health care, substance use counseling, income coaching, and more)

There definitely are people who have mental illness, which when activated or exacerbated leads to homelessness. I have family members in this boat and I've seen this cycle repeat at least a half a dozen times.

"The only way to do this is to give the person a place to live."

The people who are homeless are homeless because they, due to drugs, alcohol, or mental illness aren't safe to have around others of extreme poverty.

My friend operate several halfway houses. Almost weekly he has to kick someone out because they are a danger to staff or other clients. Generally this is at 2am, and the police are involved.

Our society has decided that institutionalizing people is inhumane. Well, if someone isn't safe enough to be in a halfway house and institutions are inhumane, the only place for them to go is the street, and, eventually, if they are lucky, prison.

> The only way to do this is to give the person a place to live. Ensure the person has healthy and decent food. This will require time and treatment so build up a new sense of safety.

> Once achieved treatment for schizophrenia could start with the drug and be closely monitored by professionals.

At least for mental illness, the US state run mental hospitals should be reopened to put the mentally ill under care, monitoring, and to get them back on medicine.

Modern psychiatric medicine could reverse the issues that used to stigmatize the mentally ill.

Improperly supervised psychiatric patients are a nightmare, if for no other reason than they often don’t take the drugs that make them not a nightmare.

That means stand-alone housing just won’t work properly.

> A majority of homeless people do not have access to even basic healthcare.

> The only way to do this is to give the person a place to live. Ensure the person has healthy and decent food.

> This will require time and treatment so build up a new sense of safety.

In many ways, just meeting people's basic needs would go farther to address mental health than any miracle drug.

Want to buy it cheaper? ALWAYS look for the molecule's CAS number in your search engine of choice.

https://www.google.com/search?q=131986-45-3 (Xanomeline) https://www.google.com/search?q=10405-02-4 (Trospium chloride)

Now you see, they're selling it with a huuuuge markup, just for that FDA's "stamp" on the box. But inside the packaging, it's just... this. But to everyone their own, I guess.

You're suggesting to people that they should buy research use only chemicals and attempt to compound them at home? That is incredibly irresponsible and dangerous.

1850$ a month at wholesale cost. That's prohibitively expensive and it could save lives.

Or end them.

If you don't trust people to compound a drug for their own use, why would you trust them to not jump off a bridge, to not kill or injure a passerby, or not to perform other serious antisocial actions? Of course this is a way deeper issue, but I tend to approach it this way. In the Western values, we tend to value freedom, also as freedom of people to self-define, very high, despite the risks it takes. And this, this is a modern part of exactly the same dilemma.

People already do exactly that, and with some basic knowledge (which should and probably will be in 20-30 years a common knowledge) it's much safer than one could expect.

Of course, it'd be ideal if they wouldn't need to worry about it and could leave this to a person who is guaranteed to be more knowledgeable in doing that, but with all the over-regulation burden, drug patents, drug schedules, it's not happening. Example of that is, precisely, the price of this. It could literally be 2000x smaller if we only get rid of that burden, which was created to give some people profit. And if we subside that with taxes, these taxes go to the pocket of a gatekept and protected-by-the-state manufacturer. That's not how taxes should even work, they should benefit the society instead.

TL;DR: This is a much wider issue.

I mean, I wouldn't compound drugs for myself for the same reason I don't do maintenance on my car's transmission myself: I don't really know what I'm doing and would probably get myself killed.

From what I understand - may be wrong - the 2000x has more to do with IP protections than production safety.

Basically, I agree. Would be great if people wouldn't have to bother. But that's a perfect world which, apparently, isn't very real. Hence, let's try to think about a solution which, even though not ideal, could possibly be better than the existing state... Because always, there is, among others, the greed of some, and so on.

By the way, I'm not even sure does IP protections itself apply here. Both parts of this fixed combination drug were known for quite some time (particularly trospium chloride is very old, also often used in research settings). But if they would apply (if the molecule itself was patentable as someone's intellectual property), they would be additional HUGE problem. But what constitutes (or creates) that "2000x" problem here isn't even that, this is most likely the FDA regulations regarding drug approvals and so on, exclusively.

It could be a good idea to wonder about, what if FDA as a governmental agency limited itself to "trusted" information campaigns to the public on efficiency of all medicines, but not doing anything which touches, notably, revenue matters of pharmaceutical companies (as that's why, in my opinion, corporations actually lobby for big FDA influence, they can make more profit off that).

Also, definitely FDA in that model wouldn't be setting themselves as an "authority" for "approvals" of drugs and so on, which for my taste is completely contrary with both the whole putative role of (federal) government, and further, with the Western values (as I outlined in my previous comment) themselves.

That new role and "definition" of FDA would be exactly akin to what NIH is doing even now in the area of nutrition. If you don't know what they do, look at the USDA FoodData Central or all the micronutrient factsheet they publish - it's my go-to resource when I wonder anything about food.

But the FDA role would then be like that, but in regard to man-made substances of medicinal use, as opposed to these occurring in abundance in nature (which, in a great simplification, when they're essential to a human body, we consider "food"). And DEA's complementary role here would be to go after manufacturers who do not label their products according to the truth.

The FDA exists to prevent us from repeating history[1] and to minimize the risk of people being killed, developing tumors, or buying placebos instead of real cures.

1. https://en.wikipedia.org/wiki/Snake_oil

That's why I said about them releasing science and evidence-based trusted information campaigns. Not about getting rid of the FDA entirely.

In the present information age, you don't need to give them such wide powers to avoid precisely what you're afraid about avoiding.

That's a very naive view of the world. There are predators waiting for deregulation to flood the market with snake oil and profit from everyone. By the time the FDA can launch any campaign, people will already have been scammed or even killed. Moreover, the information age doesn't help or prevent these issues—just look at obesity rates, despite the wealth of information and science about junk food. What you're proposing might work for a small percentage of the most informed and intellectually capable individuals, but it creates risks for everyone else.

I don't agree and I think some of what you're pointing out is because we're still in a transitional period into a full information society (which we don't even fully know what it would be, even now, 30 years deep into that transitional period, but it's inevitable and I'm personally sure that it would be infinitely better that what we have now). I think of it as a duality, that usually, when we do something good, it usually creates some harm (for example, to a group we haven't even realized it existed!).

However, your point made me realize that, in fact, probably what you generally described as the most capable individuals, are probably even now mostly immune to the harm which FDA creates as "side effects" of what they consider good. So, if we assume that FDA's action don't "touch" them in most ways, should these most capable individuals be trying to reform it? But I don't think that the FDA's action don't affect the most capable individuals much. We're all one society and even if it doesn't influence them much directly, it still very much does so in more indirect ways.

Also think, why do you think that "predators" even exist? It could be either evil nature of the humankind itself, if we assume there is such, or something else creating a place for them. If it's the first one, we're fucked regardless. But maybe it's not?

It's this https://en.wikipedia.org/wiki/Xanomeline/trospium_chloride

> M4 and M1 receptor stimulation indirectly rebalances dopaminergic and glutamatergic circuits involved in the symptoms associated with neurological and neuropsychiatric diseases such as schizophrenia and Alzheimer's disease.

Whoa. Wonder if that's being evaluated?

Yes, it's being tested for autism as well.

I wonder what their hopes are for autism. I think the detail-oriented (or at least logic-oriented) thinking at least is an intrinsic part of brain development in autistics, but I wonder if it'll ever be possible to control certain other symptoms of autism through medication.

It could very well become a cost/reward analysis thing since Autism is a spectrum disorder. People who are high-functioning will probably be fine without the drug, but people who are, for example, non-verbal may be more willing to take it.

I'm assuming such a drug would have drastic drawbacks in terms of how Autistic people think. Similar to other drugs that address mental state, they might not feel like themselves.

> I'm assuming such a drug would have drastic drawbacks in terms of how Autistic people think. Similar to other drugs that address mental state, they might not feel like themselves.

Knowing how I think, and how I use knowledge, I'm not sure that I'd be better at anything if a drug altered my ability to think in detail. Even if something made me non-autistic like magic, I have a lifetime of autistic knowledge that is structured differently than what a non-autistic brain would need. I could have to learn everything all over again if I were to become unable to comprehend/assemble the logical building blocks that I normally use to do everything.

So I have to assume the drug doesn't actually attempt to treat the core defining trait of autism and only attempts to treat some of the side effects.

As far as I'm aware, even though autism is a spectrum, every brain that is autistic has a particularly distinctive redistribution of connections, which is what results in basically everything. This redistribution is likely what results in the overly logical/analytical thinking (whether it's bottom-up or top-down), although I don't think anyone's been able to prove or disprove that, it's just a correlation.

Right, but we need to consider outcomes. If such a drug could help those who can't take care of themselves, take care of themselves, that's a very good outcome. An outcome for someone like you wouldn't be very good so it doesn't matter much. But for some, this could be the difference between being institutionalized forever versus living a somewhat independent life.

Co-administration of an agonist and an antagonist for the same pharmacophore seems like an interesting approach.

Looks like the antagonist is only outside the brain, so it works to counteract the side-effects, pretty cool.

I wanted sort of the opposite of this for opioids - work in the body, not the brain. There's been a few attempts but non that passed trials.

> I wanted sort of the opposite of this for opioids - work in the body, not the brain

That's already how some anti-diarrheals work like loperamide. And some anticonstipation drugs like oral naloxone and methylnaltrexone that work as peripheral or locally-acting antagonists

Yes but loperamide doesn't alleviate pain, which maybe just that opioids only alleviate pain if they do reach the brain, but I did see trials for non-bbb crossing ones that were for pain so not sure what's going on there.

It's possible that the analgesic and euphoric effects of opioids are one and the same. In other words, it's centrally dampening the experience of pain, both physical and mental. One is experienced as analgesia and the other as pleasure, but both may share the same mechanism, making one impossible without the other.

Would the opposite (work in the brain but not the body) also be a healthier alternative for people addicted to getting high on opiates?

A controversial and hypothetical drug which might help addicts would be a companion drug that somehow prevented the development of tolerance. I know nothing about the brain so that's probably laughably impossible, but if it existed it could cheapen the cost of a habit and lead to fewer ODs because they would have no need to chase their tolerance to feel the same effects. It would certainly have other side effects because someone could essentially just remain high 24/7 (in the extreme case).

Yeah, because it is the high they are after, but not working in the brain would make opioids completely useless for depression and anxiety (for which it really does wonders).

My want is for relieving pain in the body without making me feel high, I actually assumed you want it in the body not brain, as the brain effects are the feel-good effects, but really not sure or familiar with how they work.

Ibuprofen and acetaminophen may already be that option.

https://www.aafp.org/pubs/afp/issues/2018/0301/p348.html

I believe there are other studies besides this that points to these two OTC pain relievers as being 'just as good' as opiates.

I have went through most NSAIDs, they do not compare to opiates at all, and when I mean all, I am referring to prescription-only NSAIDs, too. There was a time when I mixed diclofenac, naproxen, and ibuprofen, too, none of them helped (separately and mixed). Kratom, however, did.

If I were to have fever, I would not take opiates though, I do not think they reduce inflammation or fever.

Maybe they work on some small subset of pain similarly, but they really are incomparable.

Opiates could near make you not feel your arm being chopped off, ibuprofen couldn’t prevent a light pinch from hurting.

There are prescription-grade NSAIDs that make Advil look like candy, but they're admittedly still not as heavy-hitting as bona fide painkillers. Great for inflammatory pain though.

They're also typically pretty rough on your GI systems. Though it's worth the trade-off, usually

Not just your GI, but they increase your risk of cardiovascular issues as well, among many others, whereas opiates do not cause any of those horrible side-effects. Dose matters, it does matter with NSAIDs, too, if I pop 10 acetaminophen, you can rest assured I will have liver cirrhosis.

Ha, also yes. Unfortunately I know this too well, but my GI systems are worse than the average person's :P

And there's even topical ibuprofen (or related nsaids)

I personally do not feel high on opiates and I tried most of them, I might be in the minority here.

Would you mind elaborating on what you've used / your experiences? I'm curious (without wanting to encourage further use) how definite it is that they don't make you high as opposed to that you need higher (no pun intended) doses to get high than other people. Are they effective at relieving physical pain for you?

It wouldn't surprise me if either were true - it's definitely the case that different people need different opiate doses to get the same effects (even for their first dose, not considering developed tolerance), I've known people for whom OTC (over the counter, no prescription needed) cocodamol - 8mg codeine + 500mg paracetamol, x1-2 per dose - contained enough codeine for them to feel a bit high, meanwhile other people like me need prescription strength (30-60mg) codeine to feel any benefits at all, and don't feel remotely high from it.

I also had a friend once who literally couldn't get high from weed, it has no effect on him - at least up to the amount tested, which was him smoking & vaping several grams of a strong strain of cannabis that got the rest of the room extremely high with much less of it. He tried on various other occasions, included edibles from a coffeeshop in Amsterdam, never any effects.

I have tried oxycodone (40 mg, went way above 80 mg too) and it did not make me high at all, people talk about a state of bliss and whatnot but I have never experienced it.

Most substances do not affect me the way they affect others; I have depression & anxiety and I have tried almost all antidepressants (along with mood stabilizers) to no effect.

I suspect it may have to do with my brain lesions (I have MS), but I am not quite sure.

That said, opiates do help with my physical symptoms, and only them, unfortunately.

> people like me need prescription strength (30-60mg) codeine to feel any benefits at all, and don't feel remotely high from it.

It is interesting though. Oxycodone is way stronger than codeine, and 80 mg is considered a very high dose yet it does not make me high, with or without tolerance.

You might have a genetic abnormality in the P450 family: https://www.ncbi.nlm.nih.gov/books/NBK574601/

My sister has defective P450 and your experience is the same as hers with opiates and other drugs, e.g. they are entirely ineffective when taken orally.

Nice to see!

This was developed in the UK for £11million and sold to Bristol Myers Squib for USD 14billion...

https://wellcome.org/news/new-treatment-for-schizophrenia-Co...

That's quite a handsome return. Which BMS feels empowered to do to since they can charge exorbitant amounts for it

I often am against the narrative that every pill should be priced at the cost of manufacturing + healthy margin, since by that logic the first pill should cost billions to cover for the R&D. In this case, it doesn't quite translate.

The Role of Childhood Trauma in Psychosis and Schizophrenia: A Systematic Review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858420/

"Childhood Trauma is probably the most important environmental factor associated with Schizophrenia. There is evidence of multiple paths between traumatic experiences and psychosis. Mental disorders are systems of interacting symptoms through a framework of networks. Psychotic symptoms in patients with a history of child abuse are more severe, persistent, and refractory to treatment. In developmental years, exposure to neglect and abuse reveals severe adverse effects on the average neurobiological growth, leading to vulnerable neurobiology preceding disadvantageous psychiatric outcomes."

https://www.theguesthouseocala.com/understanding-the-connect...

"The guiding principles of trauma-specific care can give you the space to uncover the root of your schizophrenia and trauma. Thus, understanding how your early traumas have impacted you opens the door to dismantling maladaptive coping mechanisms. As you deepen your self-understanding, it encourages you to lean into adaptive coping strategies to process your experiences and life stressors. Furthermore, with support, you can find a path to recovery from schizophrenia and trauma that considers you and your specific experiences."

i'm getting very argumentative on the internet today (under a pseudonymous account because as you might guess from my incessant posting, this issue is personal for me)

trauma (at any time), drug use, other experiences -- all can make schizophrenia more likely in those susceptible. absolutely true.

but it is a biological disease, and healing trauma won't stop its progression. as your source notes, the trauma causes differences in brain development, and once that's done its done.

i don't think coming up with a new drug, the main advantage of which is it doesn't numb you the horrible way existing antipychotics do, is a bad thing.

this is basically a drug that was only created to improve the QoL of people with schizophrenia. if society just wanted to numb them, we already have drugs for that and could just be much more aggressive in violently coercing treatment.

investing in these drugs isn't "looking away", it's putting in a huge investment of many billions of dollars to help the victims live better lives.

> once that's done its done

"As such, the hippocampus and hippocampal neuroplasticity may also play a key role in resilience and recovery from stress. This is supported by the current finding that hippocampal volume increased following psychological therapy."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943737/

"we found a significant [hippocampal] volume expansion during a 12-week treatment period, which correlated with clinical improvement"

https://www.biologicalpsychiatryjournal.com/article/S0006-32...

Increased hippocampal volume and gene expression following cognitive behavioral therapy in PTSD

https://www.frontiersin.org/journals/human-neuroscience/arti...

All those articles are for PTSD. PTSD is not the same as schizophrenia. Just because psychotherapy helps with PTSD doesn't mean it'll help with schizophrenia. Mental illnesses, and their treatments, are not fungible!

1. See my other reply in this thread about the potential link between and high comorbidity of PTSD and schizophrenia.

2. The argument brought up was that brain 'damage' "just is", and cannot be reversed; which is where any neuroplasticity research can be used to show that it is not that simple, and that even brain structures can and do continue to change over the course of a lifetime, not only on the level of transmitters.

3. The positive effects of psychotherapy for schizophrenia are well researched.

Hardy, A., Keen, N., van den Berg, D., Varese, F., Longden, E., Ward, T., & Brand, R. M. (2023). Trauma therapies for psychosis: A state‐of‐the‐art review. Psychology and Psychotherapy: Theory, Research and Practice. https://doi.org/10.1111/papt.12499

Schäfer, I., & Fisher, H. L. (2022). Childhood trauma and psychosis-what is the evidence? Dialogues in clinical neuroscience. P. 360 – 365. https://doi.org/10.31887/DCNS.2011.13.2/ischaefer

Psychotherapy does in fact help with schizophrenia. It's been a while since I was steeped in reading sources that backs this up, but one thing I came across was the notion that therapy alone is actually more effective than antipsychotics alone for certain symptoms. (If memory serves, therapy is better than drugs for persistent delusions.)

However, I think the best treatment involves both.

I’d like to call you both right on the basis that a working brain at age 40 retired with less than a working brain from age 27 or whenever schizophrenia tends to present.

Outcomes are what we’re hoping to improve. Your data looks like we get brain recovery, which is an improvement to outcomes. Necessary, maybe not sufficient.

No one mentioned PTSD?

I did!

When you look at the studies I posted initially, one theory is that schizophrenia is a result of posttraumatic stress caused by childhood trauma, and a coping strategy (flashbacks, intrusions, dissociation). It may not be in all cases, but in the cases where that is, PTSD treatment seems to work to fundamentally heal schizophrenia.

Remission of schizophrenia after an EMDR session https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820797/

Applications of Trauma Treatment for Schizophrenia https://www.tandfonline.com/doi/full/10.1080/109267710037051...

Making meaning of trauma in psychosis https://www.frontiersin.org/journals/psychiatry/articles/10....

Even if you believe schizophrenia to be first and then lead to traumatic experiences (which it certainly will), it makes total sense to do a trauma assessment and heal the maladaptive strategies and broken beliefs related to these traumatic experiences, which is where again PTSD treatment comes in.

"In the last 2 decades, it has become obvious that child abuse, urbanization, migration, and adverse life events contribute to the etiology of schizophrenia and other psychoses. […] I expect to see the end of the concept of schizophrenia soon." (Murray, R. M. (2016). Mistakes I Have Made in My Research Career. Schizophrenia Bulletin, sbw165. doi:10.1093/schbul/sbw165)

yes, there are indications for this to be true, however, it's _extremely_ hard to find clinicians willing to and courageous enough to work with patients with psychotic experiences on trauma.

basically admitting psychotic episodes kicks you out of most programs before you can even start, because the anticipated overreaction to slight triggers can only be handled by the most experienced counselors, or so they believe.

In that sense I appreciate you sharing these papers while pointing out that it's still a looong way to have this currently "esoteric" knowledge mainstream.

Trauma therapy has three components: safety from continued abuse, stabilization/resource building/(co)regulation, and confrontation. It would be ill-advised indeed to start confrontation when the other two are not in place, however it is perfectly possible to use trauma therapeutic methods for stabilizing, also for patients with psychoses.

Build a stable base camp. No need to go in deeper yet. But if you are preparing to go in and face the truth, you cannot do it with meds that blind you.

> but it is a biological disease

I want to be charitable because I think I know the point you're trying to make in your comment, and what I want to say is mostly to the side of that. But I think that this statement at best glosses over what's been a long, expensive, and heated (though sincere) scientific conversation about schizophrenia over the past century and change. It's one that not only includes a substantively fruitless search for any underlying pathophysiology, but a spirited conversation about the validity, reliability, and plain-English usefulness of the concept itself! Further, this conversation is far from the stomping grounds of cranks and scammers; it has taken place inside what you might call the most orthodox psychiatric and psychological institutions: the APA, the major high-impact journals, fancy universities etc etc.

So when an eminence like Robin Murray, knighthood and all, can go into Schizophrenia Bulletin (2017) and write something like ...

"I expect to see the end of the concept of schizophrenia soon. Already the evidence that it is a discrete entity rather than just the severe end of psychosis has been fatally undermined. Furthermore, the syndrome is already beginning to breakdown, for example, into those cases caused by copy number variations, drug abuse, social adversity, etc. Presumably this process will accelerate, and the term schizophrenia will be confined to history, like 'dropsy.'" [1]

... saying that we know it's a biological disease as part of broader claims about treatment effectiveness doesn't tell the whole story. (I encourage everyone to read Murray's reflections in the linked article, as it's a fascinating retrospective on an illustrious career in psychosis research and psychiatry.)

[1] https://academic.oup.com/schizophreniabulletin/article-abstr...

Excellent comment. A “symptom” of schizophrenia is thinking that one does not have schizophrenia. A “heads I win tails you lose” situation where the single doctor is solely and individually responsible for diagnostics and treatment, but not liable. Criminals are given more rights and protection from abuse, and the legal systems has known and documented failures. For those who are labeled mentally ill there have not been established effective safeguards to protect and support those who might speak out, and by definition of competency their perspectives are not valid. Those who are economically incentivized to argue in favor of a biological explanation can be expected to do so, despite no personal expertise in the matter, and regardless of reproducible evidence.

i think we would agree a lot about the brutality and incompetence of the current system of psychiatric institutions.

however, the reality is, psychosis frequently prevents people from recognizing their own impairment. it's just true that this is very common, and maybe shouldn't be so surprising, since in many other cases (alcohol, drugs, dementia, brain injury) people also are prone to underestimate how impaired they are.

As I read it, the parent comment is making a point about the classification of schizophrenia. It is not disputing that the condition (psychosis) is real, or claiming that people are frequently misdiagnosed with some form of psychosis.

well, okay, then we can say that a lot of people diagnosed with schizophrenia now, even if the concept of schizophrenia is not viable, do have biological disease(s) that cause psychosis alongside what we now call the negative symptoms of schizophrenia. I'm fine with that claim.

it's very different than the common anti-psychiatry claim that the schizophrenia diagnosis is a social construction that gets applied to healthy people who violate social norms.

Are there any consistent biomarkers for people with schizophrenia?

Schlesselmann, A. J., Huntjens, R. J., Renard, S. B., McNally, R. J., Albers, C. J., De Vries, V. E., & Pijnenborg, G. H. (2022). A Network Approach to Trauma, Dissociative Symptoms, and Psychosis Symptoms in Schizophrenia Spectrum Disorders. Schizophrenia Bulletin https://doi.org/10.1093/schbul/sbac122

"Ccongruent with the idea of an association between stressful life events and dissociative experiences, research has established a link between the presence and severity of dissociation and reported interpersonal traumas such as sexual, physical, and emotional abuse, with multiple traumas being linked to more severe symptoms.

In SSD populations up to 60% of individuals report a history of interpersonal trauma. The core explanation for the mechanism linking trauma and symptoms of SSD states that trauma leads to a vulnerability rendering the individual susceptible to the experience of perceptual and sensory intrusions. In line with the idea of trauma as a vulnerability factor for psychotic as well as for dissociative symptoms, studies have shown that more frequent dissociative and more severe psychotic symptoms in SSD are linked to reported trauma in a dose-response relationship."

> with support, you can find a path to recovery from schizophrenia

They misspelled "medication". There are narrow situations where very skilled psychiatrists have successfully treated schizophrenics using non-pharma (read: traditional) psychotherapy, but they are truly exceptional cases.

Being schizophrenic is not a lack of "deepening your self-understanding" that blocks them from "uncovering the root of " their illness! That is absolutely horse shit and belongs in a new age Homeopathy boutique.

Schizophrenics firmly believe their delusions and paranoia. In fact, one of the worst things you can say to them is "it's all in your head! The voices aren't real!". Commonly, they split the world into allies and suspects, so the moment you try to invalidate them, they add you to the list of agents/spirits/whatever is after them.

This disease requires a psychiatrist and medication, full stop, and is fully orthogonal to child abuse.

Hardy, A., Keen, N., van den Berg, D., Varese, F., Longden, E., Ward, T., & Brand, R. M. (2023). Trauma therapies for psychosis: A state‐of‐the‐art review. Psychology and Psychotherapy: Theory, Research and Practice. https://doi.org/10.1111/papt.12499

Schäfer, I., & Fisher, H. L. (2022). Childhood trauma and psychosis-what is the evidence? Dialogues in clinical neuroscience. P. 360 – 365. https://doi.org/10.31887/DCNS.2011.13.2/ischaefer

Schlesselmann, A. J., Huntjens, R. J., Renard, S. B., McNally, R. J., Albers, C. J., De Vries, V. E., & Pijnenborg, G. H. (2022). A Network Approach to Trauma, Dissociative Symptoms, and Psychosis Symptoms in Schizophrenia Spectrum Disorders. Schizophrenia Bulletin https://doi.org/10.1093/schbul/sbac122

etc.

Onyeama, F., Melegkovits, E., Yu, N., Parvez, A., Rodrigues, A., Billings, J., ... & Bloomfield, M. A. (2024). A systematic review and meta-analysis of the traumatogenic phenotype hypothesis of psychosis. BJPsych Open, 10(5), e146. https://doi.org/10.1192/bjo.2024.52

"there is evidence of a causal relationship between developmental trauma and psychosis, including clear temporal sequences between exposure and outcome, plausible mechanisms and dose–response relationships"

look, if someone has actually have a new drug that works like antipsychotics but doesn't have the nightmare side effects, i am very happy for that person to get filthy rich.

if this pans out the way they hope, by all means give the lead guy a couple yachts or whatever he wants. space tourism, gold statue of himself, whatever. big bonuses all the way down the org chart.

there's the potential to reduce an absolutely staggering amount of human misery here. frankly (again if this pans out) our homelessness crisis would look very different if this drug had existed 20 years ago, when the mechanism of action was discovered.

the people who cared enough and took a huge concentrated risk to do this should just get rich, if in fact it pans out.

> the people who cared enough and took a huge concentrated risk to do this should just get rich, if in fact it pans out.

They already did. Bristol Myer Squibb acquired the company behind this drug for $14 billion earlier this year.

Homeless people are unlikely to pay $20 000 per year which is the price of the drug though.

> Homeless people are unlikely to pay $20 000 per year which is the price of the drug though.

True, but think about all the people who are fully functioning and productive members of society and got afflicted with this disease. This med will increase the likelihood that they continue to be highly functioning and compliant with the treatment. This will allow them to keep their jobs and cognitive abilities.

Every person I know with this disease has trouble sticking to meds due to side effects, and not sticking to the meds and relapsing multiple times is probably one of the most important reasons that their condition regresses.

It’s not just the side effects that cause people with schizophrenia to be non-compliant with meds. Many people with schizophrenia stop taking meds because they do not think they are sick - anosognosia. It’s why a longer lasting injectable is often recommended over daily oral meds.

> longer lasting injectable is often recommended over daily oral meds

Both are recommended. Why? Daily meds are not only effective, but remind the patient that they have an illness that needs daily maintenance, it makes them involved in the treatment. Long acting injectables are added monthly to prevent backslides in case the patient forgets or does not want to take their medicine.

It would be nice if every one could afford it. And people were still filthy rich, but not necessarily exorbitantly rich? It cost the company discovering the drug around $11M

Yep the poor people will only have to wait 20 years or so for the patent to expire. I’m happy it will help people but I can still get angry at companies that will watch people die and suffer, give a shrug, and continue counting their billions.

If they're homeless because of schizophrenia, and the drug cures that, $20k/year is easily a profitable investment!

No

How completely inhumane. From a strictly numerical perspective you are correct, but it is disgusting and vile.

I know plenty of people without mental health issues who can't get jobs that make 20k and I know a few with degrees who can't.

Making healthcare a for-profit venture guarantees that poor people suffer disproportionately. Making chemicals is cheap and most of the innovation happens on government grants and funding. A government run healthcare system is obvious a cheaper solution with less suffering.

The idea is for the government to spend that $20k/year somehow (and hopefully get a big discount by buying in bulk). Spending that much on countless homeless people, and turning a large fraction of them into productive citizens, isn't "vile" at all: it would make the homeless people much happier for one thing, but would also save the rest of society a lot of money by not having to deal with the negative effects of their homelessness, plus increase the GDP and thus the tax base, easily paying for itself.

I don't think that's what they were advocating, the way I read it they were saying that people should spend that money on themselves and neglected the idea of people who couldn't afford it. But yeah if the idea is for the government to lift people out of poverty that's great we just haven't seen much of that in this country, or at least not as much as I think we could practically afford.

I wasn't really advocating anything, just pointing out that the math works.

Who might pay the $20k of course varies a lot, depending on the health care system.

One thing I've learned over the years is to not try "reading between the lines" to suss out what people are "really saying". It's just too error prone, and you rarely end up communicating.

>the way I read it they were saying that people should spend that money on themselves

I would think it's plainly obvious that schizophrenic homeless people don't have $20k to spend on anything, so I didn't interpret it that way.

Fact is, government run public health does look at numbers at the end of the day. A medicine that increases "value" (however you define that) more than it costs is more likely to get gov funding.

Turning away from the elephant in the room because it is "vile" doesn't help anyone and just entrenches the status quo.

You're looking at this in a very American Centric way, a lot of other countries figure out how medicines for very low costs. When that happens the numbers change a lot.

I'm from one of those other countries. Yes, its not as insane as america, but budgets and cost vs value tradeoffs are still a thing.

Drugs cost money to develop whether you like it or not, the only question is how exactly the money flows.

If it was taxpayer funded research it would still cost this much.

Making a public policy argument for subsidizing a helpful medical intervention isn't "disgusting and vile".

> Making healthcare a for-profit venture guarantees that poor people suffer disproportionately.

This is true of literally every industry; the poor always get less than the rich. Why not nationalize everything so that the poor always get the same as the rich? Surely if the government can run healthcare it can run toy shops and grocery stores.

Correct, this does happen in every industry. But industries are not created equal. Some are really important, and some are just kind of there.

A kid not getting a toy is sad, but it's not the end of the world. However, healthcare is literally life or death. It makes complete sense to single out healthcare.

Healthcare being life or death is why we should do anything but depend on the government to be the sole option for its administration.

This doesn't align with real-world statistics. Public options like the UK's NHS provide a higher quality of care, for a lower cost, and they're quicker in emergencies.

This isn't just the NHS, however. Virtually every developed nation's public option, because pretty much all but the US have them, outpaces the US in virtually any metric you can choose.

Not only do we pay much, much more, but we also get lower quality care. We also get slower care. We also get more extreme care.

The core issue with the private sector is they have absolutely zero incentive to provide good care. If they're smart, they should provide suboptimal care and unnecessary care - that way they can get more money in the long run.

The "free market" is not the magic bandaid to fix everything on planet Earth. You HAVE to think about incentives. What will the free market actually do here? Even a cursory, naive analysis will show the free market should promote sickness because sick people don't have options. This doesn't delve into insurance, which quite literally has an incentive to not give out treatment.

We have seen more than 100 other countries nationalize healthcare and seen it work well. Arguing against it is silly, bordering on irrational.

Capitalism simply doesn't work in an environment where one side has infinite leverage.

Even those countries, it is still a for profit verture. Companies are paid for products, Doctors and healthcare professionals are paid to go to work.

These other countries didn't nationalize their industries. They simply use spending controls. The government says we "will pay $X and you can take it or leave it". The US is rather rare in that we say "We will take it no matter the cost".

Companies are more or less greedy in different countries. They are the same companies!

By this logic anything that involves money ever is a for-profit venture, that clearly isn't the case.

Most human labor IS motivated by profit.

There can be specific individuals or organizations that seek no profit, but they are almost always working with and through other for profit entities.

To say something like an entire industry should be nonprofit is pie in the sky, which is what I am trying to highlight.

Overly broad moral sentiments like people should not seek profit when it comes to healthcare quickly break down when examined in any detail.

I think What people usually mean is simply that they think health insurance should be funded by taxes and accessible to all. Instead of simply saying this, they end up justifying it with overly broad and poorly thought out moral laws.

I agree that price feels shockingly high. However, the government can subsidize treatment. As can private insurance policies, before the sufferer becomes homeless, or if they qualify for a family member's plan.

The population suffering these illnesses are already costing the public a lot of money in various forms, it could be worth the investment.

Drugs become generic eventually and costs come down.

Zyprexa, which was mentioned in the article, is almost always prescribed as generic Olanzapine. Cost as of 2024 for generic - 9 USD, brand name 476 USD.

a necessary evil in a capitalist system. Is capitalism perfect? No. Do we know of a better system yet? Maybe. But as of right now better to have a possible cure for 20k rather then nothing.

"frankly (again if this pans out) our homelessness crisis would look very different if this drug had existed 20 years ago"

Are there numbers, for how many homeless people, are suffering from schizophrenia?

I would assume only a very small number of homeless people has the clinical condition, but those who have it, are just very visible. Most homeless people are hidden usually and avoid attention.

It's actually quite high. 10%+ in this meta-analysis, and 21% with some form of psychosis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880407/

If I were to guess, I would say that while many people may experience bouts of homelessness, the ones with schizophrenia are more likely to be persistently homeless.

this is completely true, but they take up a very disproportionate amount of time and energy from social service providers, people who work in shelters, etc, and make all spaces for homeless people much more chaotic.

the crisis would look very different if it was just a mix of people dealing with drug addiction (but basically lucid and rational) and with poverty.

"drug addiction (but basically lucid and rational) "

Serious drug addicts are seldom lucid and rational.

But I very much do get the point, that solving the schizophrenic problem, would help a lot with everything else. (I am just way more sceptical, that this drug can deliver that)

Even those who are not, will probably develop some sort of schizophrenia due to their marginal lifestyle, but I wonder if it's really a "disease", I feel like it's an adaptation to their environment for people who are more sensitive than others. I feel like the pain is more due to the lack of solutions, especially in a city centre, where it's a constant hell for these guys (and for most any other animal actually, except a few who adapted to that: pigeons, rats, some insects but not the most beautiful ones), just my thought

> but I wonder if it's really a "disease"

Not a disease but a real illness, with no cure but treatment like cancer.

Even with effective treatment, sometimes the psychosis wins, and the patient can backslide into full blown illness.

> a price in line with expected clinical benefits to patients

What would a price in line with recouping R&D and production costs and, say, a 20% profit margin be?

Bristol Myers Squibb acquired Karuna Therapeutics, the company behind Cobenfy (formerly KarXT), for $14 billion earlier this year so that’s their break even for the drug and presumably what their investors thought was fair. I don’t think Karuna had anything else interesting in trials so they have to recoup all of that from Cobenfy before they’re in the black on the acquisition.

Pharmaceutical companies offload most of the risk onto institutional investors and the public (most biotechs IPO pre-revenue to fund clinical trials) but the flipside is that they have to pay eye-watering sums to acquire promising drugs.

In their last 10-K, Bristol Myers Squibb reported an operating income of $8.4bn on sales of $43.7bn, giving them a gross profit margin of just over 19%.

https://www.sec.gov/ix?doc=/Archives/edgar/data/14272/000001...

It may not be fair math. The company may bet on 10 different things and just one pays off. It needs to pay off for the bad bets as well.

> in line with recouping R&D and production costs

That's the "recouping R&D" part.

And who invests in companies that merely recoup the R&D ?

It seems like a previous comment pointing out how investors actually fund new drug development seems to track with the loads of pharma startups working on one thing each.

Run some stock screeners on your brokerage account. You have to work to generate a list without a pharma startup on it.

A big part of this businesses model is because only large Pharma companies are equipped to handle the regulatory barriers and large enough to negotiate with the PBMs

You shouldn't look at R&D on one product, since lots fail. Would be like saying a record label that funds 100 artists with 1 being profitable should have a strict 20% profit cap on the profitable one. That wouldn't allow ongoing funding of the broader pool of bets.

How much of the record label's music production is funded by tax dollars?

David Bowie, Mick Jagger and Keith Richards, John Lennon and Paul McCartney. The list of musicians who were “on the dole” to support their music careers before they made it big is huge. It’s almost a cliche at this point. And when they do make it big, their biggest concerts are usually held in stadiums that were heavily subsidized by tax payers.

Besides, Bristol Meyers Squibb acquired this drug for $14 billion which is bigger than the annual budget of the entire NSF. For a single drug. Tax payers weren’t the ones on the hook for that.

Do record labels in the UK get funding too? I'd imagine artists getting funding is like scientists getting funding, where as record labels getting funding is more like pharmaceuticals companies getting funding.

That's fine but even considering that, is 20% only on successes enough to fund the rest of the portfolio that fails? And will it pass the risk free rate of return you can get from money markets or treasuries or whatever?

In what sense are you proposing pharma production is funded by tax dollars?

Selling a product to the taxpayers is not the same as funding.

Fundamental research slants towards public institutions, advertising and the clinical trials are the main spending the drug companies do, though they have research beyond trials too. Lots of acquiring university spinouts as well.

The gap between "one chemical that targets this thing" and a drug is massive. And basic research might not even end up with the first, just the target idea.

'Bristol Myers Squibb executives say most eligible patients are covered by Medicare or Medicaid and wouldn’t pay the list price.'

That's kind of like saying hamburger buyers are funding McDonalds.

Buyer typically do not have a direct say in how businesses are run. They exert influence by either buying a product or not.

> That's kind of like saying hamburger buyers are funding McDonalds.

If Medicare and Medicaid cover hamburgers.

I could be wrong, but it looks to me like the fact that there's a built-in government-funded ('tax dollars') market is an aspect of pharma calculations.

Absolutely it is a huge part of strategy. but simply being a customer does not give governments a vote in the internal decision making.

Customers vote by buying products or walking.

The original question was:

> In what sense are you proposing pharma production is funded by tax dollars?

I am proposing that the pharma strategy of capitalizing on Medicare and Medicaid tax dollars is a significant component of pharma production. I think this is about executive decisions rather than customer decisions.

I would agree with with the word choice of capitalizing. Funding implies you are exchanging money for control. If I fund a company, I expect to get voting shares. When I buy from a company, I expect to get what I paid for.

It is literally the same exact pharma companies selling to the US Medicare, UK NHS, and communist China. What differs is the customers.

After things got weird I got taken out by an obese guy and other nurses. Woke up in a hospital, which turned out to be a very strange week, surrounded by clues that I was going to get killed. I was let go by agreeing to an injected medication administered every month. Years later I changed to Zyprexa pills. I don't even have a doctor yet I'm taking schizophrenia pills by intertia since my mom is programmed to continue that. When I cut the dosage in half I start feeling like exercising, moving more, right now I don't feel like moving. My brain feels like it's rotting, akin to the covid mind-fog reports. I don't feel pleasure or happiness. I'm in a constant state of anxiety and self-hatred. This thing is killing me and I part of me doesn't care since it's suicidal, enjoying the punishment. My guess is that eventually I get out of this since nothing is permanent and evil is a caricature.

> What are "Novel" Drugs?

> "Novel" drugs are new drugs never before approved or marketed in the U.S.

New drugs are sorely needed

The current crop can best be described as chemical lobotomy. Impossible to focus on anything for more than 30 seconds. And it's not even a pleasant stupidity.

There's Abilify, but unfortunately doctors don't like it (due to it being perceived as less effective).

Remove the stigma of mental illness and new drugs are not really needs. The current class of drugs are excellent at controlling psychosis.

Sure there are side effects, but in this case the side effects are better than the psychotic behavior and breakdown of the patients.

Wouldn't it be better to have a drug with NO severe side effects, so we can actually get people to eat them? Which is exactly what they are trying to do. So many quit their meds, then wham another psychosis.

I just don't understand the negativity in this thread. They are doing gods work as far as I'm concerned.

RIP in peace Terry Davis. If you only had that :(

May he run over many CIA glowies in heaven <3

The audacity of pedaling a drug pricetag of $22,000 to solve someone being homeless when government safetynets won't even offer a fraction of that.

It will probably be sold for $220 in other countries.

But hopefully the compounding pharmacies and anti-pharma hacking collectives will solve the pricetag problem here.

https://www.vice.com/en/article/how-to-make-your-own-medicin...

Wait till Europe gets generics, it will cost less than $5 per month. My MS medication would cost me $8k per month in the US, costs me $2 here.

It would cost you $2 with insurance in the US too. It’s a terrible system, it doesn’t make sense, but you have to understand that approximately no one pays the list price for prescription drugs - even people without insurance.

What about those ketamine sessions for depression that cost thousands per session?

What medication?

Both dimethyl-fumarate and natalizumab are very expensive, well, MS medications are expensive in general.

Thanks. I have a relative who was recently diagnosed and I heard their first treatment was very expensive (an order of magnitude more than 8k). I was curious what medication cost 8k, as finding the true cost for drugs is often quite difficult in the US.

Most MS medications are very expensive at market price, unfortunately. :/ I would love to move to the US (because of friends), but I am afraid I will not be able to get my MS medication for ~$2 but $8k or more which I would not be able to afford. I want to switch to Tysabri (once a month injection), but it costs $1500 here at market price where I am in Eastern Europe, but I can get it for $2. In the US, it says: "The cost for Tysabri (300 mg/15 mL) intravenous concentrate is around $8,654 for a supply of 15 milliliters" (once a month supply). It does not matter though, even dimethyl-fumarate costs just as much (and is much weaker).

So... needless to say, I am lost.

Healthcare in the US is an elite graft, the system will pay the full price. That is actually why prices are so high and hospitals try to keep price tags a secret, because the bill does get paid, and all those executives and investors and even the insurance companies all make off with riches, increasingly paid for by the public. The real crime is setting up indigent people now using drugs on the street to become a massive market for psychiatric medication on the pretense of a pseudo-scientific "disorders" like schizophrenia.

> pseudo-scientific "disorders" like schizophrenia.

Are you saying you don’t believe in schizophrenia?

[flagged]

The US will do anything and everything to solve homelessness as long as it doesn't actually involve building more homes or giving homes to people.

I mean that in a fully genuine way. Just look at how much money gets set on fire cycling the same homeless people in and out of jails and emergency rooms and you can see that nobody actually cares about the amount of money being spent, but only that homes themselves aren't easier to get.

The US simply needs to undo the zoning laws, parking minimums, and setback requirements that make it illegal to build affordable housing.

First, you need a politician to say: "your home is not an investment, it's an asset."

They would be flayed. Might as well just belt out a "Dean scream" at a live event.

What qualifies to you as a home? Is it “nice”? Fully finished? Large? In a nice area? In an area with good weather? In good repair?

In short, a couple of hundred square feet with decent temperatures, a sturdy lock, and basic facilities. I believe that the de facto illegalization of SROs in US cities is one of the more prominent factors when it comes to both invisibly and visibly homeless populations.

We tore down all the slums because they were unhealthy and dangerous, and then shoved all the former tenants onto the streets.

Same basic story as asylums.

I tend to agree. Unfortunately, such places are illegal to build and rent.

School Resource Officers???

What are SROs?

https://en.wikipedia.org/wiki/Single-room_occupancy

It's a category that's been mostly legislated out of existence in the US today.

imagine thinking that the "homelessness" crisis is only lack of homes.

go talk to a sample and you'll quickly find out it ain't the lack of home.

The point of my comment, in response to its parent, is that people in the US are willing to support immense amounts of money being spent on the homeless as long as it doesn't involve housing anyone.

I think the institutional structure of most US states and cities wouldn't blink at spend huge amounts on schizophrenia drugs as long as it doesn't involve any kind of inpatient treatment (forced or not) that would put a roof over anyone's head.

For 20-30% of people it is a lack of an affordable home.

If building more homes solves 30% of the problem and this drug solves another 10%, that is 40% of homeless taken care of.

That would be a huge victory that would save hundreds of thousands of lives.

The core issue with homelessness is one of how our modern capitalist socieites are laid out.

In order to have a life, you must have a job. This is the underlying assumption that fuels everything. This assumption has a critical flaw: not everyone can have a job.

For some segments of the population, we just "bolt on" fixes to this fundamental problem. 401k's so that workers may still get their money when they no longer work. Foster care, so that abandoned babies who cannot work can still live.

For the severely mentally ill and drug addled, we haven't figured it out. The reality is these people cannot work a job and most will never be able to work steadily. Advancements in drugs may help, but even then there will always be some segment of the population who simply cannot work.

Previously, we took an "out of sight, out of mind" approach. Institutionalize these people. It's cheap, particularly if we treat them like dogs. We've evolved and realized such an approach is inhuman and evil. Now, though, what do we do?

If these people had a basic income available, they could at least pay to help themselves. This isn't a silver bullet, but I believe it's better than the current problem we have.

The true solution is fixing the fundamental problem modern society has: everyone has to work. This is really hard.

Per wikipedia, wholesale for the drug is $1,850/month.

I think I echo my prior comments on the US health and pharma system: why?

[0] https://en.wikipedia.org/wiki/Xanomeline/trospium_chloride

1. If prices weren't this high then there wouldn't be incentive to develop these drugs in the first place. There's a reason most novel drugs come from the US!

2. The vast majority of drugs do not pan out and most fledging companies formed to study them fail

3. In the US, insurance mostly covers the cost of drugs

4. In 14-20 years, the drug will be turned into a generic and the prices will plummet

> then there wouldn't be incentive to develop these drugs in the first place.

This isn't true. The incentive is to help people. There are many people who are calable of doing that but can't do it afford to. We can just pay for their cost of living and research directly, cutting out the profit entirely.

Most doctors, nurses, and even scientists dont work for free.

The incentive to help people is insufficient alone.

Rockefeller famously opened up about 1500 libraries nationwide. Free to use public libraries, but the librarians and such were paid.

Meaning, such philanthropy does not require every single soldier ant to be a philanthropist. But it does require them to not seek a "get rich" mentality. Such a mentality is inherently incompatible.

And, for the rich philanthropist, he must be ready to lose money. You and I are but lowly ants, and to us losing money is bad. But consider for someone like Rockefeller, there was 0 quality of life decrease after opening those libraries. Of course, if I open even one library, I'm broke.

Surely healthcare requires many ants who want to be compensated.

For this reason I think the idea that healthcare should not be contingent on profit seeking individuals to be a pretty hollow statement.

It also seems that we have a shortage of Rockefellers to bankroll the US healthcare system as active charity with no profit motive.

That seems inconsistent to claim that people will do the work and donate money without returns in the face of reality where very few people do that.

The response seems to be that people in our current system are forced to seek compensation to survive. This seems easily testable. Cut back doctor and healthcare workers salaries to a subsistence income or even the median and you will quickly see if people flock to the profession or leave it

This doesn't align with reality, in which almost all developed nation-states have public healthcare systems.

It is for the benefit of society as a whole that people be healthy. Therefore, it is in the interest of each and every person our healthcare be funded. Therefore, they should all fund it.

It's not like other goods where some people want a toy, and some people don't. It's more in line with education. Everyone needs it, and if everyone has it then things improve for everyone - even those who can't get it, for one reason or another.

In my eyes, healthcare as a field almost perfectly fits the description of what should be a nationalized service. We've taken the jump with other low-hanging fruit, like education. And society as a whole has benefited greatly from no longer having the majority of the population be illiterate.

Developed nation states with public healthcare systems rely on the US pharma industry for an outsize part of drug discovery. It may be better for the whole world that there's one rich country taking the private approach.

Also, the idea that if "something is in everyone's interest, it should be nationalized" doesn't address the fact that free markets are better at matching supply to demand. For example, the UK and Canada have significant healthcare supply shortages that only seem to be getting worse.

To put the previous paragraph another way: having "a right to healthcare" in the abstract is nice but if you need to see an oncologist, waiting weeks/months/years is going to get you killed. In the US this is much less of an issue. Yes it's expensive but when the alternative is "dying of cancer," people are okay going into debt!

> Developed nation states with public healthcare systems rely on the US pharma industry for an outsize part of drug discovery

I've heard this argument again and again and nobody has ever given me any hard proof.

SOME drugs are developed in the US. Not this one the post focuses on. How many drugs does the US produce as compared to the rest of the world? I dunno, nobody has any numbers. But you're assuming it's enough for it to qualify as a type of "welfare". That, to me, is more of a wishful belief than a hard reality - i.e. you're coping. The drugs are extremely expensive and it's hard to accept that maybe you're being scammed, so people retroactively create plausible reasons to explain this so they don't feel scammed. At least, that's what I see.

> In the US this is much less of an issue

This is actually incorrect. Health outcomes in the US are worse than pretty much every developed nation. This is where my previous paragraph comes in.

People would like very badly to believe our high prices are because the service is good, but this is not actually true, this is just a coping mechanism. Not only are our prices higher, but our standard of care is much lower.

> For example, the UK and Canada have significant healthcare supply shortages that only seem to be getting worse.

This is largely conservative propaganda. If you delve deeper, you will find out that wait times are typically lower in the UK and Canada as opposed to the US. Conservatives cherry pick examples of longer wait times, but again, you have to delve deeper than "oh it takes three months to get random tendon you've never heard of surgery!"

I think the point is a little different.

There is no such thing as a major US Pharma company. Major Pharma Companies and the industry are multinational. Revenue from the US is what makes drug development profitable, no matter where the companies are located. If the US paid the same as Europe, most drugs would not be economical to develop.

When you sit in a go/no-go decision to develop a new drug, you model US revenue and ROW revenue to see if the product is worth developing. US Revenue is usually 2x what can be made elsewhere, and pushes the product into the green.

The new drug in this article is Cobenfy, by Bristol Myers Squibb. Bristol Myers Squibb (BMS), is a multinational pharmaceutical company. BMS Revenues from US sales is 32 Billion. Revenues from every other country put together is 13 Billion. [1, pg 19]. The Company Bristol Myers Squibb has a profit Margin of about 14%. IF US paid like Europe, the profit margin would be -35% per year.

This is the way the US props up the global pharma industry. Now, I personally dont think this is something to be proud of. I think it would be better to simply not have many of the drugs we do, than pay the high prices. Alternatively, if somehow the US price matched with Europe, perhaps Europe would be forced to raise their prices.

The current state is like splitting the electric bill with a housemate who will only pay 25%. As long as you are scared of the power getting cut off, you are stuck paying most of the bill and being exploited.

The US health industry is deeply flawed, but it isnt just the private/public distinction. Many European countries have private healthcare and still have lower costs. It is systemic dysfunction and fear that drives the costs.

https://www.bms.com/assets/bms-ar/documents/2023/2023-bms-an...

Carnegie?

I acknowledged that in my comment, but you missed my point. They don't work for free because they can't in our current system. We can change that.

I dont think they would want to, not to the same degree.

You lack any evidence for that and are ignoring the evidence to the contrary: nurses and teachers are paid shit in almost every country but do it anyway.

They do it because they want to make money. Give them full salary even if they dont show up for work, and most wouldnt. They would rather be relaxing and having fun.

Also, Nurses are a relatively well paid position, ~150% us the US median salary.

This drug was developed for $11M in the UK, bought by a company for 18B and is being sold at outrageous prices to cover that $18B.

https://wellcome.org/news/new-treatment-for-schizophrenia-Co...

Point 1 is wrong, point 2 doesn't apply, insurance is now bearing the borden for this capitalistic endeavor for point 3, and in 14-20 years many people who stand to gain a significant quality of life improvement from this drug are likely to be dead (point 4).

Why not?

Software engineer in the US makes 100K or higher. Why?

If you have reasons to believe the price is too high, present them?

> Cobenfy, set to launch in October, will have a list price that would cost about $22,500 a year. The influential Institute for Clinical and Economic Review this year estimated that a price in line with expected clinical benefits to patients should be in the range of $16,000 to $20,000 a year. Bristol Myers Squibb executives say most eligible patients are covered by Medicare or Medicaid and wouldn’t pay the list price.

Didn't some bro from the pharma industry get mercilessly shat upon for charging so much for a life saving drug?

You're being downvoted for using an easily google-able factoid incorrectly because you're pattern matching on "high drug prices"

What happened was Martin Shekreli purchased patents for existing life-saving drugs and raised the price for them from $1.50 to $30 to cover the cost of the purchasing the patents themselves.

This is an entirely different.

How people feel about facts is much more important than the facts themselves.

The perception of the drug price increase much more than the details, along with other asshole things he did made him an easy target for outrage.

What is the cost of mass producing this new drug? How much profit should the company be allowed to make? Where's the outrage?

The company paid $14b for the research to bring this drug to market. Like all Americans — and all citizens of the world, apparently — I agree that drug prices in the US are too high, but shouldn't they be allowed to at least recoup that investment?

How can we expect companies like this to continue researching such drugs if not? Especially when, more often than not, the research leads to a dead end or failed trials, and they can't even bring the drug to market?

Legends say that Shkreli was actually trying to rip off insurance companies and left individuals alone, even going as far as to give it away for $1 to people without insurance, but I'm not sure.

I can't stand this term 'game changer', I started noticing it being used a lot during early covid and then the Ukraine war, all for things which did not turn out to be 'game changers'.

You can see its explosive rise on Google Ngrams. Looks like we're still not quite at the peak

https://books.google.com/ngrams/graph?content=game+changer&y...

Ok, we've unchanged the game in the title above.

An unfortunate requirement of modern attention/engagement economy. Readers hate this one trick, but for the media outlets, if you don't crank up hype clickbait engine to 11, you're out, or running some very niche business.

Readers hate this one trick, click to find out why!

At $22.5K/yr it'll be more money changer than game changer.

In the early days just before and just after AGI, all of a sudden a lot of games will be changed in a short period of time.

"Double down" has a similar chart, another annoying phrase.

[flagged]

Mostly fourchan tbh, I didn't notice it that much HN.

If only we had Terry Davis back...

He really was a genius. I think its inspiring how much high quality work he created all by himself. A true hacker IMO.

Quite a low comment. Terry Davis had schizophrenia and could code circles around just about anyone.

If the FDA was truly interested in game changing it would lead. As it is, it's a sock puppet for Big Pharma.

https://michaelpollan.com/books/how-to-change-your-mind/

As long as the government can’t cut deals with pharmaceutical companies it will continue to be like this. I’m sure the current SCOTUS will somehow make sure that is unconstitutional though if such a law did pass.

[flagged]

As someone with firsthand experience of a sibling with schizophrenia, this comment comes off incredibly callous and ignorant.

I encourage you to learn more about this disease because you’re gravely mistaken—it is not a transient condition of early adulthood nor is untreated isolation on anyone’s treatment plan. The disease often presents in early adulthood and is a lifelong affliction thereafter. Left untreated, the condition worsens. Drugs are taken for life because the condition is incurable.

Despite the risks, I am extremely grateful for Clozapine because it’s given me time back with my brother from this horrible disease. We’ve been through a gamut of medicines and treatments like Cobenfy are welcome. Like most families, we are jubilant at the prospect of finding better treatment options with fewer risks and side effects.

Other people exhibit psychotic behaviors because they're suffering from dementia. You wouldn't go with physical restraints if a chemical relieves the behavior?

Schizophrenia can be cured with niacin (vitamin B3). Search for Adam Hoffer's achievements

It's weird that you would state that so confidently when, as wikipedia says, "Hoffer's ideas about megavitamin therapy to treat mental illness are not accepted by the medical community." It didn't pan out.

Didn't pan out because it's not the plan to pan out. The plan is to make people think there's something wrong with them and recycle them with insurance.

It didn't pan out because attempts to replicate it didn't work. He seems like another LSD abuser who thinks every idea they have is good or maybe a grifter who wanted to maintain interest in fruitless theories.

[dead]

Every single time someone has told me a disease could be cured with vitamins, it was scurvy or bullshit.

Enzymatic cofactors (vitamins) many not a be cure, but maybe a better, cheaper, less harmful, treatment. Take pyridoxine (B6) as an example.

Also, did you know vitamin C deficiency not only casues scurvy but mood disorders as well? The neuropsychiatric effects of vitamin C deficiency: a systematic review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302360/

on Pyridoxine:

Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12613

Vitamin B6 deficiency hyperactivates the noradrenergic system, leading to social deficits and cognitive impairment https://www.nature.com/articles/s41398-021-01381-z

Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study https://pubmed.ncbi.nlm.nih.gov/11838627/

Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis https://www.jpn.ca/content/43/3/194.abstract

Treatment of Pyroluric Schizophrenia(Malvaria) With Large Doses of Pyridoxineand a Dietary Supplement of Zinc https://isom.ca/wp-content/uploads/2020/01/JOM_1974_03_4_11_...

[dead]

Does anyone else feel like this is just some sort of population control measure?

The schizophrenics certainly do!

https://my.clevelandclinic.org/health/diseases/23348-paranoi...

If you have ever known someone suffering from schizophrenia then you would know they are keen to not suffer from schizophrenia. The disease itself is a form of population control, as few who have this condition live a full natural lifespan. Since 2020 I lost two friends age 50 and 40. Both very high functioning people with college degrees who were never homeless.

No, what’s your rationale?

They already have Chemtrails and TV for that.

"Netflix and chill" is surely a different take on "population control".

Let's remember it was recently proven that there is little to no evidence that serotonin levels are linked to depression: https://www.nature.com/articles/s41380-022-01661-0

It's pretty much likely to be the same deal here.

Since there is no chemical or biological test one can do to confirm a schizophrenia diagnosis, it's a subjective diagnosis by practitioners, treating such subjective diagnosis with powerful brain-chemistry altering drugs. Worse, we do not yet know whether these new drugs will be easy to get off of. Some of the other anti-psychotic type medication is VERY hard to get off of, such as abilify, where most drug treatment centers will not deal with Abilify withdrawals or take on those patients because those are so severe (extreme violence, self harm, etc during withdrawal).

Until Psychiatry can reform itself to become a real science, using the scientific method (repeatable, provable results and not just a "theory of how brain chemistry maybe works sorta but we're not sure"), it will continue to just be a big cash cow for Big Pharma while hooking many patients who do not need these drugs onto them for life, while failing to effect ANY cure on the things they are treating (Have you heard of someone getting "better" after taking anti-depressants and being able to come off them? No. They have to take them for life. That's not a cure.)

> Have you heard of someone getting "better" after taking anti-depressants and being able to come off them? No. They have to take them for life. That's not a cure.

Some people with acute depression can take the meds, work on the underlying issues and taper off, yes.

People with chronic depression likely need to take the meds for life.

People with type I diabetes can't get insulin one time either. People with allergies often take the allergy meds when exposed to allergens, which is always for some.

That's not big pharma being greedy, that's a chronic condition requires chronic treatment.

I'll raise my hand here. Took antidepressants for a year. Successfully weaned off of them. Have not had recurrence of symptoms.

I needed the boost to be able to get out of bed often enough to do the work in therapy. That led to being able to take other actions that helped my brain chemistry too, like eating better food, which reduced inflammation, and getting outside more often.

My doc said her experience was about half and half. Half of people were able to wean off successfully. Half ended up deciding it was better to stay on.

Recovery does happen. For lots of us.

My experience was the same; they were like a bandage we put on to allow us to heal without infection, for me SSRIs were a mental bandage so I could heal enough to get to a psychologist. I came off them, and was fine. My situation is confounded by my buprenorphine script though, as it's known to be a reasonbly effective anti-depressant in it's own right, albeit via a completely different mechanism (it's an opioid-receptor agonist, partial agonist and antagonist. Weird drug)

This is so misguided that it's hard to even know where to begin. People who develop high blood pressure without a known underlying cause take a pill for it every day for the rest of their life. You could say the same thing, they're not cured, but what actually matters is that they get to live a full life, unconstrained by the disease even if we don't know the underlying cause. Of course it would be better if we were more advanced of a civilization and figured it out, but the important thing is that these people get their lives back.

We don't have cures for diabetes, HIV/AIDS, allergies, plenty of ailments. Having treatments is totally valid even if they are taken forever.

People with the guidance of their doctor stop taking antidepressants all the time. External factors aren't static and often these can change. (separately or because of the treatment) You do not need to stop treatment unless you and your doctor have decided it is going to be better for you.

Another point I'd make is that we don't have exact mechanisms for action in other treatments like paracetamol. That doesn't make it invalid treatment.

What is your doubt about paracetamol? This drug's pharmacology is rather well understood.

About the analgesic activity https://pubmed.ncbi.nlm.nih.gov/31734950/

About the antipyretic activity https://pubmed.ncbi.nlm.nih.gov/29738273/

i'm curious what is the longest conversation you've ever had with an untreated schizophrenic person?

it's so obviously a "real disease" even if we don't fully understand the biological basis. it's subjective but honestly, there are just a ton of completely obvious cases.

abuses of the psychiatric system are very bad, but schizophrenia is so so clearly real.

> Have you heard of someone getting "better" after taking anti-depressants and being able to come off them? No. They have to take them for life. That's not a cure.

There is no medicine in the world that you can take for a limited time to fix problems forever. That's not how medicine works. That's not how the world works.

Antibiotics (Most of the time) Everything surgery, I would include gene replacement therapy and auto transplants in its viccinity.

Yes there are? Antibiotics for one.

And those that change gene expression, like Accutane for acne.

An enlarged salience network may be responsible for depression in some patients[0]. Some individuals are pre-disposed to being depressed and it may be a chronic condition, like any other chronic condition. For others, it could "simply" be a chemical imbalance that taking medication for a set period of time resolves (lucky them).

[0]https://www.nih.gov/news-events/nih-research-matters/mapping...

I work as an EM scribe and routinely see patients experiencing psychotic episodes. My background is in neuroscience and I'm interviewing for med school right now.

> it was recently proven that there is little to no evidence that serotonin levels are linked to depression

This has been the consensus of the psychiatric community for the last 20+ years. The serotonin hypothesis was heavily pushed in marketing as a way to medicalize depression and convince people to seek treatment for it. Probably a net positive when it comes to reducing stigma, but few people have been seriously arguing the serotonin hypothesis. As it takes about a month for effects to kick in, most people believe that it's compensatory changes to the brain that happen in response to upregulation of serotonin, such as downregulation of 5ht2a which has an overdensity in people with depression.

> Since there is no chemical or biological test one can do to confirm a schizophrenia diagnosis, it's a subjective diagnosis by practitioners

This is true to some degree - we don't have a blood test or an fmri scan that will definitively point to schizophrenia, the diagnosis is (for now) based on DSM criteria and by thoroughly ruling out other causes of schizophrenia. We do have tests for a number of other causes of psychosis, like lumbar punctures for NMDA-receptor encephalitis.

I'd like to emphasize that there are MANY diseases and conditions that we treat empirically for based on subjective symptoms which are just as real as schizophrenia. There are no tests we can perform for concussions or migraines. The brain is very challenging to perform tests on because of the blood-brain barrier and the skull.

> Worse, we do not yet know whether these new drugs will be easy to get off of.

Cholinergic drugs are VERY well understood and used in the treatment of a number of diseases. This "new" drug is a drug that was discovered 20+ years ago and is being used in a creative way to mitigate its GI side effects. Everything so far points to this being more effective at treating the negative symptoms of schizophrenia (loss of motivation, cognitive impairment), with milder side effects (some mild GI issues which typically resolve after a few days), which is a huge deal considering how many people with schizophrenia quit dopaminergic drugs due to the side effects.

One of the biggest problems with our for-profit system is that schizophrenia is comparatively rare and largely affects those with a lower socioeconomic status, so there isn't a huge financial incentive to work on schizophrenia drugs. This one was being developed for another purpose entirely.

> Until Psychiatry can reform itself to become a real science, using the scientific method (repeatable, provable results and not just a "theory of how brain chemistry maybe works sorta but we're not sure"), it will continue to just be a big cash cow for Big Pharma while hooking many patients who do not need these drugs onto them for life, while failing to effect ANY cure on the things they are treating

It sounds like you have an ax to grind against the profession, but I can assure you that there is a huge need for it and that people largely see benefits from medication. For me, SSRIs got me stable and functional so I could better address the root causes of my depression. Psychiatric drugs aren't perfect, but for many people they're truly life-saving. There is evidence to support kindling in some diseases such as bipolar as well - that if you remain unmedicated, manic episodes become progressively worse as the brain becomes more damaged.

Additionally, psychiatrists treat more than just depression. Some specialize in sleep medicine, addiction medicine, toxicology. They are trained to tease apart primary depression from other non-psychiatric diseases masquerading as a psychiatric disease. I saw a patient once who had been treated with a number of antipsychotics by his PCP and mid-level providers for persistent visual hallucinations. He met with a psychiatrist who tried increasing his anti-seizure meds, which resolved what was likely a recurrent partial seizure.

Every drug (sans some off-label use) goes through an FDA approval process and is, over the course of several years and millions of dollars, shown to be effective and relatively safe. I can assure you that psychiatry is as scientific as any other field of medicine. It's still in its infancy compared to some other specialties - the brain is a very complex organ and difficult to study - but we have as good of an understanding of most psychiatric illnesses as we do neurodegenerative diseases such as Alzheimer's, which have been equally as difficult to study and treat.

Psychiatry is not even close to the most profitable area of American healthcare. Psychiatrists are one of the lower-earning specialties, and most people with mental illness never obtain treatment for it. Compare that to the 10% of all seniors who are on Eliquis to prevent blood clots, which costs a thousand dollars a month without insurance.

Trust me, if there was a way to permanently cure a psychiatric disease with one procedure or pill, we would all be in favor of it. Just because a diabetic needs to take insulin for life doesn't make endocrinology a scam.

> by thoroughly ruling out other causes of schizophrenia.

This never happens. "thoroughly" never happens. There are many examples of this. Recently a woman who was in psychiatric care fro over 20 years was finally diagnosed with Lupus (NPSLE) and cured.

They did not thoroughly do anything for me. I had to figure it out for myself.

> people largely see benefits from medication

I have a friend with depression and they had her on two adrenal receptor inhibitors (trazadone and risperidone) and she only got worse. They they went to ECT. She had severely constipation (treated with yet another drug, Linzess) and hypotension as well. They they started her on ECT, which did not work and she lost some memory.

The doctors failed to see that adrenal blockers could be causing her depression. I showed her the science, she asked her doc to stop those meds. She she no longer depressed nor has hypotension or consipation. And now she is angry.

They diagnosed her with schizophernia after they started her on antidepressants 25 years ago.

I am not saying medication are not sometimes useful, but I cannot count the times I have seen patients get worse on psych meds.

> He met with a psychiatrist who tried increasing his anti-seizure meds, which resolved what was likely a recurrent partial seizure.

You are still in med school so I hope you learn more. Anti Seizure meds have been the go to for these disorders fro years. They put me on depakote for my modo disorder 20 years ago.

> Psychiatry is not even close to the most profitable area of American healthcare.

Psych pharm businesses are very profitable though, and that is what we are talking about here.

> Trust me, if there was a way to permanently cure a psychiatric disease with one procedure or pill, we would all be in favor of it.

There is not pill, but there is a method. It is called Personalized Medicine.

And by the way KaRXT is not going to work. You should learn about receptor density changes when people take these receptor modulating drugs. This is why they always fail. There are better ways to manage the glutamate/GABA balance if that is the persons issue which it many cases it may not be, or may not be the fundamental problem. And if the acetylcholine is the problem in schizophrenia, why does M1 and M4 receptor in the body have bad side effects but whil in the brain it is good?

I will tell you why, they are using this drug to sedate the patient, not treat the patient.

After one meeting with her doctor, they gave my daughter antidepressants a the class of drug that’s meant to be taken for life. She was just an angsty teenager during covid.

She didn’t take them, shes fine, but yall are the devil frfr

Admit this: if you go to a doctor and say anything about the inside of your head that makes them uncomfortable you’re getting a chemical lobotomy immediately

It's significantly better now, because your daughter didn't get a real lobotomy. Which was the expected treatment for a young woman who misbehaves.

It's not typical to get antidepressants after a single meeting with a general practitioner. In fact, I don't even know if that can happen.

That being said, depression is real, and it does take lives. I've known many people who have successfully survived depression via SSRI's and no longer take them. That's the flip side you're not seeing. I've also seen unmedicated people take their lives.

-Appeal to worse problems

-Gaslight and hand wave

-Slippery slope

I do agree that women are disproportionately affected by the over prescription

I would argue that you're doing the same thing. You're hand waving and gaslighting people who were/are helped by SSRIs. You're appealing to a worst-case scenario, where someone who does not have depression is immediately prescribed medication (incredibly rare, in fact not sure if this can happen). And you're claiming a slippery slope by extrapolating this to other mental health issues and psychiatry as a whole.

https://www.sciencedirect.com/science/article/pii/S014067362...

Here is the drug trial results for EMERGENT-2 which was one of the two phase-3 trials that lead to the approval.

I think its striking that the trial is only 5-weeks long and this medication gets approval.

From your linked paper:

> Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia.

EMERGENT-4 and EMERGENT-5 concluded last year [1], which was the reason for the approval. EMERGENT-2 was mostly a milestone Karuna Therapeutics used to get enough funding for the rest of the trials and inform their design.

[1] https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-...

Thanks for the info - curious to look at these trials and see if there are sustained long term positive outcomes on the PANSS or these are just safety /tolerability studies.

The FDA is under regulatory capture by the pharmaceutical industry, and their approval or lack thereof is one of the most unreliable measures of the safety and efficacy of psychiatric drugs in particular. Schizophrenia diagnoses are almost entirely subjective in nature (there's no reliable biochemical or biomolecular or biophysical test for the presence or absence of the condition) - really the whole field of psychiatric care for mental health issues is about as useful as tuberculosis experts were in the 1850s, before Koch's demonstration of the infectious microbial nature of the disease.

I’m sort of surprised to see someone claiming schizophrenia is subjective. Schizophrenia has extraordinarily pronounced symptoms. It’s like claiming lupus doesn’t exist because there’s no single reliable diagnostic test for it. Schizophrenia has very specific and easily observed symptoms and is specifically affected by medications such as Zyprexa that doesn’t cause similar changes in behavior for people without schizophrenia or psychosis. However that and related medications have horrible side effects leading most patients to avoid taking it. For people who are or have family members ravaged by schizophrenia this is some of the best news you can imagine - a medication with similar beneficial effects on their loved ones but without turning them into zombies. It feels callous to an extraordinary degree to deny the existence of schizophrenia and to not recognize the benefit to a minimal side effect mediation that can give the schizophrenics life back.

This is actually a ridiculous answer. So you claim if you get get cold turkey'ed on Zyprexa you won't hallucinate or have mania? You claim, there are people out there, who take a dopamine antagonist without getting diabetes, organ issues, loss of self (fundamentally this is what these drugs do, deprive of brain function) and ultimately sudden death?

I made no statements remotely like this.

> Schizophrenia has very specific and easily observed symptoms and is specifically affected by medications such as Zyprexa that doesn’t cause similar changes in behavior for people without schizophrenia or psychosis.

By the nature of these drugs, each and every symptom of what you pronounce Schizophrenia would be your daily life once on the poisonous neuro-toxic agents.

This doesn't seem science-backed and feels more emotional.

Whatever feels for you emotional or not is irrelevant. It is science-backed that each and every "Schizophrenia" symptom of a book that resembles the bible and nothing else (going by the name of DSM) is a product of chemically induced damage and torture with neuro-toxic poison.

It is not science-backed the schizophrenia is caused by schizophrenia medication. That doesn't even account for people who have psychosis evident of schizophrenia but have never taken medication.

> It is not science-backed the schizophrenia is caused by schizophrenia medication It truly is. The fact psychosis can be caused by alchohol withdrawal even (delirium) is irrelevant. Psychiatric "medications" directly cause schizophrenic symptoms and everything, hallucinations included. They not only lobotomize people, but also cause tremendous suffering and non reversible permanent damage. If you really believe all this, you should check your facts straight.

Do you have any sources for this? No offense, but this sounds a bit crazy. Again, this doesn't account for people who are unmedicated and clearly have symptoms. Schizophrenia doesn't seem to be caused by Schizophrenia medication, that doesn't even make sense. How would they get the medication then?

The "medication" is not something anyone gets better with. They become easier to deal with and they essentially live less, both in terms of effective living (thinking, talking, creating) as well as long-term living (life span reduction). As far as your request per sources, here it is:

https://www.madinamerica.com/critical-psychiatry-textbook-2/

A background on the author:

https://en.wikipedia.org/wiki/Peter_C._G%C3%B8tzsche

I feel like you don’t know anyone personally who has schizophrenia or you wouldn’t dare to say this. People tend to develop schizophrenia in young adulthood and it’s not after taking antipsychotics they take antipsychotics after developing schizophrenia. Schizophrenia existed before the development of antipsychotic medications, that’s why they were developed at all.

There’s nothing to glorify in schizophrenia- it’s in many ways worse than losing your loved ones in a tragic accident. It’s even worse for the schizophrenic who after having a normal life descends into paranoid delusion and take on an existence of misery.

I know the right answer here is for me to ignore and walk on but it’s hard to do so and leave statements like these unqualified.

I dare to say this because I really know what I am talking about. Every symptom of what you call "Schizophrenia", cited by the bible-like book going of the name DSM, is directly caused by dopamine antagonists. I am not saying "Schizophrenia" does not exist by itself, I am just saying that it's being categorized as well as treated in a specific manner on purpose. There are far better alternatives and remedies one could actually utilize to achieve better therapeutic results. And by the way, it has been scientifically proven that people without "medication" do better long-term.

Pain is entirely self reported by the patient. There is no objective measure of it. Painkillers must also then be a scam, by your logic.

I see this take on the internet a lot usually combined with some statement of how Schizophrenics are secret geniuses and were the prophets of olden times. It just doesn't square off with my own observations of schizophrenics in real life. How is the condition subjective when you see the same types of symptoms across people? I've seen it with men and women afflicted by the condition - always the persecutory delusions, belief that they are some king or prophet/chosen one, disorganized thinking, and word salads. Why is it always the same symptoms? You're telling me that's not rooted in any common condition?

> always the persecutory delusions, belief that they are some king or prophet/chosen one, disorganized thinking, and word salads. Why is it always the same symptoms?

https://en.wikipedia.org/wiki/Martha_Mitchell_effect

Your argument is as good as calling Martha Mitchell crazy and dismissing entirely possible organized exploitation on a premise of made-up symptoms that are composed of zero scientific evidence.

No it’s under pressure from people who go to the press saying “the FDA won’t let me use this drug to help me/my family” who ignore “because there’s no evidence it works” as the reason.

The pharmaceutical just has to tell those people that it does work in their particular case and just ignore the studies that say it doesn’t, and the media and politicians uncritically report that as “the FDA is mean, let pharmaceutical companies sell new and expensive snake oil and re-victimise these people”, then in a few years later the same reporters and politicians berate the “ineffectual” FDA for allowing snake oil.

Regulatory capture doesn’t mean the entire of idea of FDA as a safety mechanism is bad… nor does a legitimate reason for their existence mean that capture doesn’t exist

It is good to hold federal agencies with large power to a very high standard. But that’s often not the case as any critiques get dismissed with the “well they have good intentions and can you imagine if they didn’t exist?” hand wave tactic.

> Game changer in treatment of disease we can't even define

Doesn't quite have the same ring to it, now does it?