[HN Gopher] Schizophrenia drugs may have been off target for dec...
___________________________________________________________________
Schizophrenia drugs may have been off target for decades, study
finds
Author : thedday
Score : 128 points
Date : 2023-08-15 14:24 UTC (8 hours ago)
(HTM) web link (www.msn.com)
(TXT) w3m dump (www.msn.com)
| robinduckett wrote:
| I know someone who has diagnosised but untreated schizophrenia.
| She was admitted to the hospital after she started having thyroid
| problems and they also administered schizophrenia medication
| while she was in. The change in her behaviour was positive and
| dramatic and allowed her to start accepting help after being
| scared that men in white coats would take her away if she ever
| let on about her illness to anyone. Now she has been out of
| hospital for a while, unmedicated again and back to her old
| behaviour including talking to people who aren't there and having
| bad episodes. Maybe some medications are off the mark but
| whatever they used for her absolutely worked.
|
| I realise a sample size of one anecdotal piece of evidence is
| hardly scientific, but I'm getting rather tired of the constant
| mouse model studies, with barely related parameters.
|
| I wish there was a better way to do medical research, in actual
| human beings. Unfortunately it seems historically that actual
| human medical research is mired in the suffering of the
| (generally unwilling) participants.
| P_I_Staker wrote:
| Her first instinct was right. That "medicine" could just have
| easily been poison. Now you're seeing that the medicine didn't
| even work.
|
| These people are like dementors, sucking your lifeforce away.
| It is right to be scared of them. You should be scared of
| people that are trying to hurt you.
|
| Her providers next course of action will be to gaslight her,
| and blame her for her condition as will most of society. Even I
| blamed a destructive friend for not taking meds.
|
| You and I probably have different definitions of "worked", but
| mine is better. Does she have it now? Does this generally
| happen to patients like her, etc.? Then it didn't work. It's
| not the patients fault your methods suck.
| crooked-v wrote:
| Medication only works while you take the medication.
|
| Do you also object when taking a few aspirin doesn't make all
| headaches stop for the entire rest of your life?
| ChrisClark wrote:
| > Now she has been out of hospital for a while, unmedicated
|
| You're wrong, it obviously worked. Might want to check into
| your own beliefs about why the doctors are trying to sap all
| your bodily fluids.
| P_I_Staker wrote:
| I don't think you read my comment. This issue is actually
| highly contentious.
|
| If a remedy consistently has poor results, it's a bad
| remedy. Simply saying "it works for the ones that are
| righteous" is absurd. If you break it down that's generally
| what people are saying, but usually use words like lazy,
| stupid, crazy, addict, etc.
|
| If most patients can't or won't follow a treatment maybe it
| doesn't work so well.
|
| > Might want to check into your own beliefs about why the
| doctors are trying to sap all your bodily fluids.
|
| This is very insulting, and demeaning, not to mention
| untrue. At no point did I imply doctors are trying to sap
| me of my "bodily fluids". I've never believed anything
| close to that. A leach sucks body fluid, so I guess it's a
| bit like that, but metaphoric.
|
| You seemed to care about your friend. I don't see the point
| in blatant bigotry towards mental illness.
| A_D_E_P_T wrote:
| Situation normal.
|
| Consider the discovery of valproic acid:
|
| "Valproic acid is a carboxylic acid, a clear liquid at room
| temperature. For many decades, its only use was in laboratories
| as a "metabolically inert" solvent for organic compounds. In
| 1962, the French researcher Pierre Eymard serendipitously
| discovered the anticonvulsant properties of valproic acid while
| using it as a vehicle for a number of other compounds that were
| being screened for antiseizure activity. He found it prevented
| pentylenetetrazol-induced convulsions in laboratory rats. It was
| approved as an antiepileptic drug in 1967 in France and has
| become the most widely prescribed antiepileptic drug worldwide.
| Valproic acid has also been used for migraine prophylaxis and
| bipolar disorder."
|
| To this day, nobody knows exactly how it works, apart from the
| fact that it hits more than a few targets. (And it's a
| particularly potent inhibitor of the epigenetic modulator histone
| deacetylase.)
|
| Apart from a subset of very clear-cut cases -- steroid hormones,
| peptide hormones, and certain aggressive chemotherapeutic drugs
| -- there's no clear model for most small molecule drugs. Even
| really mundane ones like metformin and paracetemol are very
| imperfectly understood.
| Ezku wrote:
| Your point is a very important one. Do we check the
| interactions of a tentative drug molecule against every single
| molecular target in the body, and do we track what happens as a
| result of all those interactions? It's quite common that a
| group of "usual suspects" on the researchers' radar get checked
| for -- but by necessity, _a lot_ of ground goes uninvestigated.
| > Consider valproic acid: For many decades, its only use was in
| laboratories as a "metabolically inert" solvent for organic
| compounds
|
| Speaking of "inert" solvents: > Dimethyl
| sulfoxide (DMSO) is the most common organic solvent used in
| biochemical and cellular assays during drug discovery programs.
| > Despite its wide use, the effect of DMSO on several enzyme
| classes, which are crucial targets of the new therapeutic
| agents, are still unexplored. > 1-4% (v/v) DMSO, the
| commonly used experimental concentrations, showed ~37-80%
| inhibition of human acetylcholine-degrading enzyme,
| acetylcholinesterase (AChE)
|
| (DMSO: A Mixed-Competitive Inhibitor of Human
| Acetylcholinesterase. ACS Chem Neurosci. 2017
| https://pubmed.ncbi.nlm.nih.gov/29017007/)
|
| Oops! How many investigations on specific drugs were in fact
| showing mostly the results of what happens when interfering
| with one of the most ubiquitous-yet-underappreciated signalling
| systems, the cholinergic system?
|
| I'm hoping widespread & systematic application of modern
| methods like in-silico molecular docking studies will lead to
| much fewer such oversights.
| _Wintermute wrote:
| That's what controls are for, you're always comparing against
| the DMSO control. I also don't think anyone who's doing small
| molecule screens thinks DMSO is inert.
| aatd86 wrote:
| Normal might be a strong word. It messes with the brain which
| is the core.
|
| Goes to show a lot of clinical medecine is about short-term
| relief and not necessarily about real health.
|
| If you really look at it with unbiased eyes, between elective
| surgeries and what not, it's not really about curing any true
| dysfunction sometimes. Perhaps too many times.
|
| We just go with the flow but, heck, MDs are not even
| necessarily healthier than you, some even smoke to this day!
|
| Go figure...
| crooked-v wrote:
| You've gone off on an unrelated tangent here. "Situation
| normal" in this case means that, as with lots of drugs, we
| only poorly understand the mechanism by which they actually
| work, and that new discoveries can completely change our
| understanding of how to use and improve on them.
| Aurornis wrote:
| The study used a mouse model where amphetamine is used to
| simulate schizophrenia. Obviously, it's not guaranteed to map to
| real humans having real schizophrenia.
|
| That doesn't mean it's a useless result, but everyone should
| remember that research is an accumulation of decades of many
| little pieces of information. This is another clue, not a "nail
| in the coffin" of old theories.
|
| The ultimate evaluation of medication is how well it actually
| performs in studies. If someone can develop a new medication that
| is more selective for D1 and show that it performs better and/or
| has fewer side effects then this would be a great result.
|
| However, don't get too excited. The pharmaceutical industry is
| often 10 steps ahead of public findings like this. A selective
| D1/D5 antagonist with negligible D2 affinity has already been
| trialed for schizophrenia without good results:
| https://en.wikipedia.org/wiki/Ecopipam
|
| Many of the most prescribed schizophrenia medications already
| have significant D1 affinity, too, so it's not really correct to
| say that we're "off target"
|
| These findings tend to be very aggravating to computer scientists
| who are familiar with systems that (mostly) obey clear-cut rules
| and can examined in extremely fine detail with enough equipment
| and motivation. Neuroscience is not so simple, but that doesn't
| mean it's all wrong. Each finding is one more piece of the
| puzzle.
| fragmede wrote:
| While everyone should be keenly aware the limitations of taking
| experimental results in mice and extrapolating to humans (aka,
| they often _don 't_), doesn't that mean what we really have, is
| a bunch of well tested medication for meth addicts? Which; if
| there was a way to get meth addicts off meth, would be a boon?
| monknomo wrote:
| It's not for addiction, but yes, if someone takes enough meth
| to induce psychosis, antipsychotics will reduce the
| psychosis.
| chrsig wrote:
| To be fair, there is a meth problem in the US.
|
| Also there's a huge chasm between lab grade amphetamine and
| street meth.
| freeone3000 wrote:
| This wasn't tested and wasn't purported to test countering
| either addiction or acute overdose. This is a study showing
| the method of action. In mice (and humans, D2 receptor
| agonists are not new drugs), we have a method of countering
| the psychosis effect of meth. This has some value in ER and
| rehab settings where it is currently for healthcare provider
| safety; there is no evidence that it does anything else.
| edgyquant wrote:
| Not necessarily addicts. You don't have to be addicted to
| achieve psychosis you just need to take a certain amount. For
| me this amount is pretty small, I was prescribed adderal for
| awhile and even 20mg was enough to induce serious paranoia
| and the occasional hallucination
| winrid wrote:
| One of the more popular Schizophrenia drugs also cause diabetes
| :(
| psychphysic wrote:
| One?! It's pretty much all second generation... Metabolic side
| effects could probably be used to define SGA!
| Pixie_Dust wrote:
| > One of the more popular Schizophrenia drugs also cause
| diabetes :(
|
| Not to mention, weight gain leading to type two diabetes,
| thyroid problems leading to fluid retention in the legs and
| memory loss. Not much of a cure :(
| Pixie_Dust wrote:
| My Schizophrenic friend tells me the difference between
| schizophrenics and normal people is that normal people can hear
| their own thoughts whilst schizophrenics can hear other peoples.
|
| Serious point, maybe schizophrenic symptoms are cause by a
| disruption in REM sleep. As in the suffers are experiencing a
| waking dream. Some time back they did an experiement on students
| and kept them awake for days-and-nights on end. Eventually they
| couldn't tell the difference between the dreaming and the real
| world.
| kayodelycaon wrote:
| Many things can cause psychosis, so it's difficult to draw
| cause and effect out of the data.
|
| I've experienced severe psychosis. For me, it was a merging of
| reality and imagination. I always knew what was real, but my
| brain couldn't filter and ignore the unreal. I would act as if
| imagination was reality though I knew it wasn't.
|
| Several people I've talked to have said similar things.
|
| I think of dreams as the result of rebooting the brain mid-
| defrag. It's chaotic in some way. My experiences with psychosis
| was far too structured and self-consistent to be a dream.
|
| My theory is there is an active component to psychosis that
| doesn't fit in with REM sleep as a cause.
| wheelerof4te wrote:
| That's because their brains were rebooting when their body
| senses low activity.
|
| Kind of like sleep function on laptops. Otherwise, the brain
| cells would "overheat".
| cududa wrote:
| This analogy is wrong on so many levels.
|
| Human sleep would be more aptly related to garbage collection
| and indexing - neither of which occur when a laptop sleeps.
| When a computer overheats it throttles performance and
| sometimes shuts down.
| wheelerof4te wrote:
| When a brain overheats, you can easily lose consciousness
| and be forced to sleep. Wheather you like it or not.
|
| So, not that wrong as you might think.
| yuck39 wrote:
| Link to the actual paper:
| https://www.nature.com/articles/s41593-023-01390-9
| justsomeguyhere wrote:
| So I've tried half a dozen antipsychotics, here are my 2 cents:
|
| The only things those drugs did to me were making me comatose,
| poop my pants, sleepy, dumb and hungry.
|
| You can't be declared psychotic or paranoid, when the only thing
| you can do is sleep, drool, poop yourself, and make 3 words
| sentences, so lazy doctors think these drugs work.
|
| But they don't, there was zero change in my beliefs, fears,
| anxieties, I was the exact same person, only slower, dumber, and
| sleepier.
|
| And at some point, when you're exhausted from being a zombie, you
| end just lying to your doc and pretending everything is fine,
| even when you believe doctors should always know the truth,
| because it's the only way to stop yourself from staying a brain
| dead zombie for life and causing irreversible damage.
| thrw238592 wrote:
| This happens because the meds deplete your body of vitamins and
| minerals. The information on this was very scarce some years
| back, but the info is starting to get out.
|
| Here's a link on the subject:
| https://www.optimallivingdynamics.com/blog/7-important-nutri...
|
| A good & strong vitamin B complex, magnesium & zinc are a
| starting point. Your doctor or psychiatrist SHOULD tell you
| this. For some reason this seems to be something people have to
| find out for themselves.
| FollowingTheDao wrote:
| SO glad to hear someone bring this up!
|
| All these meds are metabolized by CYP 450 genes which need
| heme. The more drugs to take the lower your heme. To make
| heme you need B6, Zinc and Riboflavin.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034403/
| kayodelycaon wrote:
| You do need to be careful adding vitamins and supplements
| without medical guidance.
|
| For example, magnesium can interact with medications. I can't
| actually take it because there isn't a safe, reliable time in
| my daily medication schedule for it.
| tredre3 wrote:
| I recognize myself very much in your words. I've also tried
| everything and it does not change my beliefs, fears, crippling
| anxiety one bit. Let alone improve my mood. Thankfully does
| help with mania. But the side effects are pretty bad and the
| doctors I've met tend to dismiss them, especially the more
| esoteric ones.
|
| So I have to lie to doctors to steer them towards the care I
| really need. I would prefer not to lie. I tried not to lie. But
| when you tell them you want to quit or go as needed, they
| gently suggest committing you or lose interest in you. They see
| you as a toy to experiment on. It's impossible to be treated
| like an adult. It's infuriating.
| at_a_remove wrote:
| Schizophrenia is a strange illness. We've had two successes (by
| some metrics) in psychiatric treatments because the science aimed
| at schizophrenia but hit something else: lithium and
| electroshock.
| psychphysic wrote:
| The pharmacodynamics of antipsychotics is such a rich topic, yet
| this article is so crap!
|
| Surprised no mention of pimavanserin (which doesn't act on
| dopamine useful in those with Parkinson's and psychosis) and that
| L-dopa can reliably induce psychosis (used on Parkinson's).
| M1ch431 wrote:
| The entire paradigm for treating schizophrenia and other chronic
| mental states is flawed.
|
| Mental distress/disorder cannot be treated properly because of
| the strong for-profit motive (unrestricted greed) that these
| privately-owned (sometimes publicly traded) mental hospitals and
| pharmaceutical companies have.
|
| Mental hospitals are effectively a prison. Locked doors, removal
| of rights once committed, coercive and sometimes forced treatment
| and restraints, being told that you have a lifelong disease (with
| no measurable physical damage -- fMRI scans are not indicative of
| damage) that needs drugs for the rest of your life, and getting
| billed an exorbitant amount - to name a few things that are
| wrong.
|
| If your rights are violated and you are declared incompetent
| (which is pretty common if you are unstable or in crisis), it's
| an uphill battle in special courts called Mental Health Courts.
| It's difficult to get a second opinion from a third-party
| psychiatrist, or to contest treatment orders (such as mandatory
| intramuscular antipsychotic injections or ECT which respectively
| have a very potent and long-term effects).
|
| The conversation needs to be shifted towards the Soteria House
| paradigm.
|
| This article sums this model of care pretty well:
| https://www.madinamerica.com/2019/09/soteria-house-heal/
|
| They have very impressive results, particularly in regards to
| schizophrenic and psychotic patients, and do not use life-long
| tranquilizer prescriptions to achieve their results. It needs
| more study, it needs more implementation, but the core of the
| model is that it builds a supportive community around vulnerable
| people -- instead of caging and viciously profiting off of these
| people.
|
| I spoke on this matter in the past, and you can read my thoughts
| here: https://news.ycombinator.com/item?id=34029719
| rybosworld wrote:
| It's amazing how far the medical world has come in treating
| ailments of the body, but we've made comparatively little headway
| in ailments of the brain.
| FollowingTheDao wrote:
| Last I checked my brain was part of my body. And that is why so
| little headway has been made, people keep thinking the body and
| brain act independently of each other.
| toasted-subs wrote:
| There's a million reasons why. And I can't get into it without
| being called a quack.
|
| And yes, washing hands is common practice now.
| maybelsyrup wrote:
| You're correct overall, and I know what you mean. But to offer
| a small and somewhat provocative nitpick: these (the psychoses
| or any other so-called mental illness) aren't "ailments of the
| brain", as they've never been shown to be. None has any
| demonstrated underlying pathology, much less a clinically
| useful one.
| throwaway60707 wrote:
| You sure?
|
| Schizophrenia is directly linked to dopamine. So is ADHD, but
| in the opposite way (not enough dopamine). Both were
| demonstrated on fMRI.
|
| Psychosis is a physical issue in the brain (too much dopamine
| making the brain fire when it shouldn't) that's solved by
| administering dopamine antagonists (= antipsychotics).
| atchoo wrote:
| There is little surprise that if a brain is behaving
| differently, that we can see differences in
| neurotransmitters. Like the Serotonin Hypothesis, that
| doesn't mean the neurotransmitters themselves are part of
| the physical cause and not just a consequence.
|
| It's like trying to diagnose and treat a political crisis
| by observing telephone connections. We see stark changes in
| telephone use in a crisis. If we meddle with the telephone
| exchanges we might improve or harm various types of event.
| It's not really about the telephone calls though, we are
| just hacking at the messaging of an external event we are
| ignorant of.
|
| A conspiracy theory induced panic might be superficially
| "solved" but cutting all the the phone lines. We have not
| identified or solved the cause though and people don't find
| life without telephones (dopamine) worth living so they
| plug them back in (quit their anti-psychotics).
| copperx wrote:
| Were any of the fMRI studies validated? I thought all
| related research was discarded.
| throwaway60707 wrote:
| I looked and didn't see any such news. Do you have any
| links?
| maybelsyrup wrote:
| There are dozens, but this is one of the most clear and
| to the point, and is found in one of the most mainstream,
| orthodox, and hard-to-get-published-by journals in mental
| health:
|
| https://sci-hub.ru/10.1001/jamapsychiatry.2020.1941
|
| The citation is:
|
| Weinberger, D. R., & Radulescu, E. (2020). Structural
| Magnetic Resonance Imaging All Over Again. JAMA
| Psychiatry. DOI:10.1001/jamapsychiatry.2020.1941
|
| The article is a follow-up editorial on an older (2016),
| more substantive critique of MRI methods in psychiatry,
| which is also worth digesting slowly:
|
| https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.201
| 5.1...
|
| The citation is:
|
| Weinberger DR, Radulescu E. Finding the elusive
| psychiatric "lesion" with 21st-century neuroanatomy: a
| note of caution. Am J Psychiatry. 2016;173(1):27-33.
|
| The situation is about as bad as it can be: there are so
| many potential sources of confounding in MRI studies that
| they simply cannot be trusted to say anything about the
| basic cellular elements of brain tissue in either healthy
| or diseased patients. All they can validly talk about is
| themselves; in other words "rather than referring to
| differences as evidence of brain structural
| abnormalities, they should be called _differences on MRI
| measurements_. "
|
| This is without getting into other hugely problematic
| aspects of MRI studies in mental health: tiny samples;
| failure to replicate; and most interesting to me, the
| fact that experimental subjects (i.e. the people in the
| study "with ADHD" or schizophrenia or whatever) are not
| screened for psychiatric medication use, which, because
| medications can shrink brain tissue, can make it look
| like the condition is affecting brain structure when in
| fact the drug is. (So another source of confounding,
| then.)
| cyberax wrote:
| > None has any demonstrated underlying pathology
|
| Mechanical damage to parts of the brain can cause personality
| changes. Multiple neurological syndromes are directly linked
| to macroscopic brain changes. This includes schizophrenia,
| traumatic brain injuries dramatically increase its risk.
|
| We also know that schizophrenia almost never happens along
| with epilepsy. They are almost mutually exclusive.
|
| It's fair to say there is no single macroscopic trigger for
| schizophrenia, but that's it.
| pixl97 wrote:
| If instead of saying brain you say "The most complicated
| structure found in the known universe so far" it starts to make
| a little more sense on the enormity of the problem at hand.
|
| Most organs are composed of one or only a few types of cells
| and their particular arrangement doesn't matter that much. For
| example swapping kidneys between people doesn't change who they
| are (mostly, smaller edge conditions apply here). But we can't
| swap brains because the brain encodes your 'youness'.
| BurningFrog wrote:
| You can also think of "the brain" as a collection of 10-20
| separate organs, rather than one super complex one.
| Filligree wrote:
| Those 10-20 organs are all individually super complex...
| pixl97 wrote:
| While true, the complexity of each organelle in the brain
| is still much higher than that of the typical organ
| elsewhere in the body. That and there is a high degree of
| connectivity and feedback between components where the API
| is completely and totally undocumented. It's not that you
| don't know what the known API calls do, you don't have any
| clue on how many API calls there even are. Accidently
| emulating one of these calls when attempting to trigger a
| different behavior can lead to wildly unexpected outcomes.
| wheelerof4te wrote:
| I just love the programmer's analogy here.
| whatscooking wrote:
| We haven't gotten far at all. We treat symptoms, not diseases
| tcj_phx wrote:
| Strictly speaking, psychosis is more strongly related to excess
| serotonin, 'the molecule of stress and inflammation'. Doctors
| sometimes recognize 'Serotonin Syndrome' in their ER patients:
| "too much serotonin causes signs and symptoms that can range from
| mild (shivering and diarrhea) to severe (muscle rigidity, fever
| and seizures)." Usually the Serotonin Syndrome is caused by a
| combination of prescriptions, or street drugs.
|
| https://www.mayoclinic.org/diseases-conditions/serotonin-syn...
|
| All the effective anti-psychotics seem to have anti-serotonin
| properties, in addition to their anti-dopamine effects. For
| example: "there are also recent studies that 'stumbled upon' the
| 'shocking' evidence that anti-dopamine drugs commonly used for
| treating schizophrenia such as haloperidol are actually potent
| serotonin antagonists as well." - http://haidut.me/?p=1297
|
| One of you quoted my essay _Cargo Cult Psychiatry_ in a comment
| on Sunday, on a submission of Feynman 's _Cargo Cult Science._ I
| responded, then thought to submit my link to the original at Mad
| In America again: https://news.ycombinator.com/item?id=37110874
|
| This paragraph from that comment is essential for helping anyone
| diagnosed with the label of "schizophrenia":
|
| "The good news from the mental health world is that Chris Palmer,
| M.D. published Brain Energy [0] last year. I haven't read more
| than excerpts from google books [1]. My understanding is Dr.
| Palmer was a conventional palliative psychiatrist, then he had a
| patient whose schizophrenia improved on a ketogenic diet. The
| patient was able to discontinue antipsychotics: Dr. Palmer's mind
| was blown. Then he discovered the 70+ years of research
| establishing that mental health conditions are metabolic problems
| that can be successfully treated with pro-metabolic therapies.
| Perhaps the most bold and disruptive aspect of Brain
| Energy is understanding precisely how and why medications
| that harm metabolism might reduce mental health
| symptoms. The long-term consequences are of great
| concern and require the urgent attention of the
| psychiatric community.
|
| -Chris Palmer, MD -
| https://twitter.com/ChrisPalmerMD/status/1687850270602981376
| [...]
|
| [0] https://brainenergy.com/ / [1]
| https://books.google.com/books?id=FoxlEAAAQBAJ&pg=PT233&dq=B "
| psychphysic wrote:
| pimavanserin case in point
| tcj_phx wrote:
| Thanks for the tip: Pimavanserin has a unique
| mechanism of action relative to other
| antipsychotics, behaving as a selective inverse
| agonist of the serotonin 5-HT2A receptor, with
| 40-fold selectivity for this site over the 5-HT2C
| receptor and no significant affinity or activity
| at the 5-HT2B receptor or dopamine receptors.[2]
|
| -https://en.wikipedia.org/wiki/Pimavanserin
| gvb wrote:
| https://archive.ph/sZerh
| whats_a_quasar wrote:
| The brain is really complicated, and all psychiatric medications
| affect multiple receptors and subsystems. Framing this study as
| "antipsychotics were off target" is an editorial choice. The
| title could just as easily have been "Improved understanding of
| antipsychotic action means we may be able to design better
| antipsychotics."
|
| Edit: It also ought to be noted that the study was on mice that
| had been given amphetamines to mimic psychosis. Which is
| interesting and good science, but seems far from enough evidence
| for the press to write stories with headlines like "Everyone Was
| Wrong About Antipsychotics" or "Schizophrenia Drugs May Have Been
| Off Target For Decades, Study Finds."
|
| This sort of internet story bothers me because I've spent time
| around schizophrenics who are recovering from a psychotic
| episode. Schizophrenia can get really, really bad, in a way that
| I don't think most people who haven't had contact with the
| psychiatric medical system understand. Antipsychotics have awful
| side effects, but for many people the alternative is uncontrolled
| psychosis, which can be vastly worse.
|
| There's a decent chunk of people who inherently and vocally
| dislike psychiatric medication, and these media stories are in
| that tradition. But the only people who ought to be involved in
| the decision about using antipsychotics are the patient, their
| family, and their medical providers. Writing headlines that are
| too broad for the evidence that supports them does not help
| improve the lives of people with schizophrenia.
| hinkley wrote:
| The serotonin model of antidepressants just doesn't pass a
| sniff test. Something else is going on there. How they say they
| should work would mean they work in the first dose and possibly
| that don't require tapering off. But that's not what happens in
| the real world.
|
| If we understood what's really happening we could target
| pathways better.
| [deleted]
| mtlmtlmtlmtl wrote:
| The "serotonin model", actually called the monoamine
| hypothesis, hasn't really been taken seriously in the field
| for decades, except by naysayers like yourself who continue
| to use it as a strawman.
| dontknowwhyihn wrote:
| Don't people still talk about "low seratonin levels?" I
| always found it suspect that we say someone's levels are
| low without actually measuring them.
| astrange wrote:
| Yes, and psychiatrists never believed it was "low
| serotonin" at all, or at least claim to have never
| believed it.
|
| For ADHD, stimulants actually do treat it by fixing "low
| dopamine"... in specific areas of the brain. But "low
| dopamine" is also a description of Parkinson's disease.
|
| But SSRIs don't work like stimulants do; they take a lot
| more than half an hour to take effect. We don't actually
| know how SSRIs work in the people where they do work.
| FollowingTheDao wrote:
| > But SSRIs don't work like stimulants do; they take a
| lot more than half an hour to take effect.
|
| Sorry, need to be an anecdote for you. Prozac makes me
| manic in about 5 hours. We know how SSRIs work, the
| problem is they are treating a symptom not the cause of
| depression which is immune dysfunction.
|
| If SSRIs did not increase serotonin there would be no
| risk of them causing serotonin syndrome, and they do.
| hinkley wrote:
| The fact we still called them SSRIs is the part that gets
| me. But I suppose until we know how they actually work we
| can't just call them "thingy".
| PawgerZ wrote:
| They Inhibit the Reuptake of Seratonin Selectively. What
| should we call them?
| astrange wrote:
| If they do something else as a side effect, but it turns
| out that's the main effect, it might be worth renaming
| them.
| kayodelycaon wrote:
| Most brain-altering drugs have effects beyond just the
| main target. See this chart for an NDRI:
| https://en.wikipedia.org/wiki/Bupropion#Pharmacodynamics
| mtlmtlmtlmtl wrote:
| They're called SSRIs because pharmacodynamically, that is
| what they do. Not sure what's so wrong with that.
| AmericanChopper wrote:
| > hasn't really been taken seriously in the field for
| decades, except by naysayers like yourself who continue to
| use it as a strawman.
|
| ...and by basically the entire general public. Big pharma
| did a great job on the "depression is a just a chemical
| imbalance..." awareness campaign, but absolutely dropped
| the ball on the "actually we were wrong about that"
| campaign, so that's still what most members of the public
| tend to believe.
| mtlmtlmtlmtl wrote:
| Can you name one topic of bleeding edge research on which
| the general public's understanding is not either
| outdated, oversimplified, or both?
| AmericanChopper wrote:
| The reason it's outdated in this case is because the
| pharmaceutical industry invested so much money and time
| into selling Prozac to the public, for a treatment that
| was ultimately ineffective, and then of course invested
| no money at all into correcting the public's subsequent
| misunderstanding. So unlike what you've claimed, this
| isn't a concept taken seriously only by naysayers who
| want to use it as a strawman. It's a concept many members
| of the public generally believe to be true, because the
| experts spent so much time and money telling them it was.
| pigeonhole123 wrote:
| There seem to be practitioners still taking this seriously,
| and I expect them to continue to do so until they die.
| According to this article from 2022 it's still
| "influential":
| https://www.nature.com/articles/s41380-022-01661-0
| faeriechangling wrote:
| I see patients still take it seriously because of the heavy
| marketing of Zoloft in particular.
|
| The drugs are literally have serotonin in the name.
|
| I still hear people regularly refer to mental health
| problems being due to a "Chemical imbalance", often as a
| way to defend their use of pharmaceuticals and dismiss the
| efficacy of any other intervention. It's that they see
| people justify a non-falsifiable in the efficacy of the
| current course of treatment. It's that it's hard enough to
| convince people who have been on SSRI's for decades and are
| doing badly to take a month to ween off them, a month to
| see how things go, and a month to get back on them. If they
| believe their brains are fundamentally broken without
| evidence it's just about impossible.
|
| It's that when a sixth of American women have taken
| anti-d's in the past month, and the most popular
| explanation as to why is they have broken brains that need
| to be treated with medicine, as if their problems must all
| be due to some genetic issue or whatever, I find it
| abhorrent.
|
| I don't know, it pisses me off that these drugs are popular
| largely due to a mythology and how difficult they are to
| stop more than they're efficacious is all (not that they
| are not efficacious). It's not that psychiatrists don't
| know this theory isn't true, I'm well aware the theory has
| been well known to lack support for a long time in medical
| circles, it's that they don't effectively inform their
| patients.
|
| Medicine should stop calling them "SSRIs" if the SSRI part
| is a tangential side-effect, better educate patients on the
| fact that medicine doesn't really know why the drugs work,
| or even if a given patient will respond to them better than
| placebo. Governments should ban pharmaceutical
| advertisements because they make people sick and
| misinformed.
| pseudalopex wrote:
| SSRIs are popular because they are effective and safer
| than older antidepressants. And what depression
| interventions are incompatible with SSRIs but other drugs
| not understood completely also?
|
| What should SSRIs be called if the SSRI part is how they
| work indirectly? What would you call them now? And SNRIs?
| And MAOIs?
| cududa wrote:
| I mean this without sarcasm, but congratulations on your
| deployment the phrase "strawman" being one of the only uses
| I've ever seen that makes sense, and not using it as cop
| out to avoid responding to a valid metaphor/ anecdote
| FollowingTheDao wrote:
| As someone living with schizoaffective bipolar disorder and
| has studied his own genetics over 15 years I can tell you
| serotonin plays a role in mood disorders but it is secondary.
| (Tryptophan is pushed down the kynurenine pathway during
| illness and therefore none is available to make serotonin.)
|
| https://www.mdpi.com/ijms/ijms-22-11714/article_deploy/html/.
| ..
|
| My mood disorder is caused by an immune disorder. How do I
| know this? When I take TNF Inhibitors my mood disorder goes
| away. But it is all over my genetics (PNP, CACNA1C, EARP1,
| TNPAIP3, SLC18A2, SLC1A2, SLC23A2 are the most relevant) and
| I have found rescue in high dose zinc and ascorbic acid not
| only for my mood, but also for my Ankylosing spondylitis.
|
| Note as well that I had my worst paranoid delusional states
| both time I had COVID.
|
| Here is a tip from a two time suicide survivor; Doctors can
| only treat the symptoms, and most do its poorly. Use medicine
| to get stable and stay alive but figure out the rest on your
| own.
| wk_end wrote:
| How antidepressants work doesn't seem especially germane to a
| discussion of antipsychotics?
| cududa wrote:
| Antidepressants can exacerbate symptoms/ trigger episodes
| in patients with undiagnosed schizophrenia and bipolar, so
| it is pretty relevant
| kristianp wrote:
| Yes, I agree. It's confusing to branch off to that without
| mentioning why they are doing so.
| hinkley wrote:
| Neurochemistry isn't relevant?
| Broken_Hippo wrote:
| _The story could just as easily be "Improved understanding of
| antipsychotic action means we may be able to design better
| antipsychotics"_
|
| And that would be a more accurate understanding of it - and I
| hope its true. Current antipsychotics are helpful but
| imperfect.
| aatd86 wrote:
| I think you might miss the point slightly, moving too far the
| discussion on the other side.
|
| It's perfectly normal to wonder how can one administrate
| something when one doesn't understand it. Especially when there
| can be such debilitating effects.
|
| In clinical settings, things are way less clear than you make
| it seem. All psychosis are not equal and even all diagnostic of
| a same patient are not equal.
|
| There is a lot more caution that should be advised. Including
| in the administration protocols instead of handwaving and just
| claiming that it should be taken life-long (which betrays that
| it's not a cure).
|
| It does not even make sense in the first place that there is no
| attempt at finding the base neuro-transmitter levels in and out
| of psychotic phases for each patient before deciding on the
| posology of a treatment. Managing plasma concentration in a
| finer-grained way might avoid some (not all) of the issues with
| neuroleptics.
|
| Some people even only have a few episodes every few years and
| are still put on life-long treatment with all the side-effects
| that can then be seen.
|
| It needs to be way more fine-grained if not restudied.
| retrac wrote:
| > It's perfectly normal to wonder how can one administrate
| something when one doesn't understand it. Especially when
| there can be such debilitating effects.
|
| A theoretical/principled understanding of how a drug works
| has never been required for useful medicine to happen. For
| example, we don't know how general anaesthesia works. We
| don't know why some people have extremely bad reactions to
| certain anaesthetics (and they do). And yet they are used
| every day, to enormous net benefit.
|
| > finding the base neuro-transmitter levels in and out of
| psychotic phases for each patient before deciding on the
| posology of a treatment
|
| Is it actually possible to measure that, non-invasively?
| kbelder wrote:
| It isn't required for useful medicine, but it is useful for
| required medicine.
| aatd86 wrote:
| The anaesthetic agent is not a drug that one is supposed to
| take for the remaining of their life and has no observed
| side-effects in general.
|
| It's also treated with the utmost care and in most
| interventions, if there is a choice to do without, the
| patient is offered the choice. There is a lot more consent
| involved.
|
| So it's not the same thing.
|
| To answer your other question, yes, neurotransmitter levels
| can be measured in the blood or urine.
|
| For someone under-treatment, it would only make sense to.
| Wait 4 or 5 times the half-life of the molecule. (that's
| the difficulty since once started, they are not even
| supposed to stop).
| horsawlarway wrote:
| > The anaesthetic agent is not a drug that one is
| supposed to take for the remaining of their life and has
| no observed side-effects in general.
|
| This is notably untrue. General anaesthesia is associated
| with higher risks of dementia. Especially the older the
| person being treated.
|
| While there's some disagreement here - short term
| cognitive decline is inarguable as a side-effect (called
| post-operative cognitive decline), and many suspect it's
| related to long term cognitive issues:
|
| ---
|
| From: https://www.alzheimers.org.uk/about-dementia/risk-
| factors-an...
|
| > There is a link between surgery and short-term changes
| in thinking and memory, called post-operative delirium or
| post-operative cognitive decline. This condition
| particularly seems to affect older people. Some studies
| have also found that these short term changes may be
| associated with higher risk of dementia later in life but
| other studies have found no association.
| aatd86 wrote:
| I don't see how your link establishes that what I said is
| notably untrue.
| whats_a_quasar wrote:
| The goal is to maximize the life outcomes and quality of life
| of people with schizophrenia. I think in the conversation
| here there are two questions: What should the public
| conversation on schizophrenia be like? And, how should the
| medical system use antipsychotics in the treatment of
| schizophrenia?
|
| I think, on the first question, the public conversation about
| schizophrenia is not ideal for improving outcomes. In
| particular, people in their 20s who have a first psychotic
| episode need to be pushed by their friends and family to get
| medical care immediately. Schizophrenia treated early is
| associated with much better outcomes later in life, and long
| periods of untreated psychosis are associated with much worse
| outcomes. I think that poor quality articles like this one
| sustain that section of the population who distrust
| psychiatrists, which leads some schizophrenics to seek
| treatment too late or not at all.
|
| On the second question, I think that doctors are doing about
| as well as they can with antipsychotics with the current
| state of knowledge. Though it sounds like your concern about
| overprescription is from experience, and my feelings about
| the right level of long-term antipsychotic use are much
| weaker than my feelings about the public conversation.
|
| I agree that it would be better for antipsychotics to be
| better targeted. Measuring individual neurotransmitter levels
| sounds like a very interesting way to better target
| treatment, though I don't think it is straightforward to
| measure neurotransmitters in a living brain.
|
| I agree that many patients are on antipsychotics for longer
| than is necessary. The challenge is distinguishing between
| patients who should discontinue antipsychotics and the
| patients who will immediately relapse into psychosis without
| meds.
|
| ---
|
| Other thoughts:
|
| > It's perfectly normal to wonder how can one administrate
| something when one doesn't understand it.
|
| This is a mischaracterization of the state of the science.
| Antipsychotics are well understood, though not fully
| understood. We at this point have decades of data on the
| efficacy of antipsychotics, the prevalence and severity of
| side effects. We know most of the interactions between the
| drug and the body. What is not well understood is the exact
| mechanism by which these interactions moderate psychosis.
|
| > there is no attempt at finding the base neuro-transmitter
| levels in and out of psychotic phases for each patient before
| deciding on the posology of a treatment
|
| To my non-expert ears this sounds like an interesting
| approach to make treatment more targeted. I am not aware of a
| technology that could currently be used to measure
| neurotransmitters in a living brain, and I worry that
| measurement would be invasive.
|
| > Some people even only have a few episodes every few years
| and are still put on life-long treatment with all the side-
| effects that can then be seen.
| 11235813213455 wrote:
| I was diagnosed with schizophrenia, given some strong
| antipsychotics, it was a disaster I could barely talk or hand-
| write properly, gained 15kg. Fortunately I didn't listen the
| advices and stopped after 4 months, my therapy now is just
| walking, running, cycling, outdoor, trees, vegetable, minimalism
| m_0x wrote:
| Pardon my ignorance and prejudice, but how are you not a danger
| to the people that surround you?
|
| Or is schizophrenia a spectrum very much alike as autism?
| FollowingTheDao wrote:
| hey, that was a pretty, uh, stigmatizing statement.
| schizophrenics are no more of a danger to others than the
| general population. It is because society treats them like
| shit and so they take drugs to cope that makes them violent.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852683/
|
| "Patients with schizophrenia without comorbid substance abuse
| have only a slight increased risk of violent crime compared
| with the general population, suggesting that substance abuse
| plays a mediating role."
| wheelerof4te wrote:
| "Or is schizophrenia a spectrum very much alike as autism?"
|
| It is exactly that. There are a lot of people with pcychosis-
| related symptoms who go about their lives without treatment.
|
| They experience attacks once in a blue moon, but that is just
| about it. A few calming words or moments alone help.
| TeaDrunk wrote:
| Schizophrenia can be more or less severe. A schizophrenic
| with very mild symptoms, a stable life, access to food and
| shelter, no unhandled trauma, etc. can function and even
| thrive without medication. The disease can also get better
| with age.
|
| Consider: you can hear voices and choose not to respond to
| them. You can have delusional beliefs and not act on them.
| There's no functional difference between talking with your
| mom on the phone and talking with an alien that has replaced
| your mom on the phone if you're willing to play along or
| simply acknowledge "hi schizophrenia, funny idea, that".
| wheelerof4te wrote:
| On point. Many people know that they have this problem and
| can act before it manifests in reality, through action.
| whats_a_quasar wrote:
| Schizophrenics are less violent than the general population.
| In general, schizophrenia is not dangerous to others around,
| even untreated. People who are in a psychotic episode act
| oddly, which can scare others, but the perception of danger
| comes from that erratic action, not from actual danger.
| FeteCommuniste wrote:
| "Individuals with schizophrenia are 4 to 7 times more
| likely to commit violent crimes, such as assault and
| homicide [4,5], and 4 to 6 times more likely to exhibit
| general aggressive behavior, such as verbal and physical
| threats [10,11], compared with the general population."
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852683/
|
| That isn't to say that schizophrenia necessarily causes the
| violent behavior: the two variables might not have any
| causal relationship at all. But the correlation _is_ there.
| tredre3 wrote:
| > Fortunately I didn't listen the advices and stopped after 4
| months, my therapy now is just walking, running, cycling,
| outdoor, trees, vegetable, minimalism
|
| Over-medication is a big problem, but you have to recognize
| that you are extremely lucky to be able to function without it.
| Not everybody can. I couldn't.
|
| I share your experience regarding side effects, it would likely
| kill my career. Thankfully anti-psychotics work quickly, unlike
| antidepressants. As long as I have the discipline to recognize
| the signs, I can medicate mostly as needed. But this, again, is
| a privileged situation. More severe cases can't risk that "as
| needed" treatment.
| 11235813213455 wrote:
| Right,my case is light (I've always had a job, at least
| between major burnouts), and the injections were way too big
| for my weight. It was efficient as I was calm at that moment,
| I started reading books again, but I lost all my passion for
| things, my brain was like mostly turned off, that's why I
| preferred returning to the previous state and finding other
| solutions
| calibas wrote:
| I have a theory. Antipsychotic medications just need to make the
| person more "manageable" to be considered effective. It doesn't
| need to eliminate the psychosis directly, it could just make the
| person more sedated, and it would appear to be "working"
| properly.
| cududa wrote:
| That's not really your own theory, that's like, the specific
| goal of psychiatric treatment? You can't "cure" schizophrenia
| or bipolar, the goal is to manage it.
|
| My dad developed severe mental illness later in life, destroyed
| his life, and never found a regiment that worked for him before
| his death (undiagnosed congenital heart condition is what ended
| up getting him).
|
| I think anyone who has schizophrenia or bipolar (and their
| loved ones), would happily take medically "managed" psychosis
| over the hell of unmanaged psychosis
| calibas wrote:
| You're mixing up managing a disease and managing a person.
| Managing (treating) mental illness is not simply about making
| the person more manageable for others.
|
| There's drugs that reduce or eliminate hallucinations for
| many schizophrenics, so it's something you can treat (except
| in unfortunate situations like your dad or my uncle). There's
| a big difference between a medication that actually removes
| the symptoms over one that sedates a person, they're not the
| same and one is obviously preferable.
|
| There hasn't been enough concern about how the drugs work, or
| why they often cause serious side-effects like tardive
| dyskinesia. It's simply enough that the person becomes
| manageable for others.
|
| These drugs have been around for a long time and only now is
| someone investigating deeply into how they actually work.
| merricksb wrote:
| Same study discussed previously:
|
| https://news.ycombinator.com/item?id=37057135
|
| (50 points/3 days ago/51 comments)
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