10 ms·

The brain is really complicated, and all psychiatric medications affect multiple receptors and subsystems. Framing this study as "antipsychotics were off target

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

Lutger 3y ago
This media story isn't 'in the tradition' of vocally disliking psychiatric medication. You could twist the headline to be, possibly. Have you read the article itself? Its the complete opposite. The headline is a bit attention grabby perhaps (and of course, that is what a headline must do), but I wouldn't even call it clickbait. It is even fairly accurate. Yes, they were likely off target with the specific neuroreceptors, no that doesn't mean the medication didn't work and of course, this is a positive development for designing better medication. This is classic storytelling, draw the reader in with some conflict and save the resolution for the end. We need to be able to discuss negatives and limitations associated with psychiatric medication in an honest and nuanced way. They often don't work well enough, there are costs associated and just giving somebody a pill and be done with it is hopelessly inadequate to the point of negligence. As someone who did experience uncontrolled psychosis myself, let me tell you the absolute taboo of discussing these matters made me way more uncomfortable than the side effects. Furthermore, psychiatry made me feel like a diseased animal at times, not to be taken very seriously and just put on drugs for life to be on the safe side. In hindsight I do appreciate how difficult that line of work is, doesn't change my experience. I am not against medication really, actually I think they are a must-have. I just think most anti-medication people are not really rallying against the side effects or at least not initially, but grew opposition out of bad experiences with treatment that focuses only on medication and was just very inadequate. Medication is what represents that. Additionally, medication can come to represent your loss of sanity and with that, you fundamental not-belonging to the group of 'normal people'. Thus the desire to not be on meds 'for life'. Haven't spoken to a single therapist or psychiatrist who made me feel that was a legitimate desire and who understood that. Maybe things have changed, this was a long time ago. To deal with the resentment against meds, I think it is way more effective to address those concerns directly and without fear, rather than putting down everything that might be interpreted as negative about medication. Like you say, without experience yourself, you have no idea how bad psychosis can get. It is a really complex thing and you will need much, much more than pills. And not only for the psychotic episodes, because these experiences tear at your identity as a human being. It isn't over when the psychosis is over.
Broken_Hippo 3y ago
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.
- deleted 3y ago
  [deleted]
- Lutger 3y ago
  You'll be positively surprised to read the conclusion of the article then: "The findings also offer a glimmer of hope that researchers can correct course and use these new insights to design much-improved treatments for schizophrenia. Treatments that can't come soon enough." Close enough, right? Journalists know how to write headlines that make people read the article, or at least some people. They are little dramas, and if you start by giving the plot away like that, as if you just simplified a scientific paper a bit, your analytics will tell you to look for a different job soon. It is what it is. So no, it couldn't 'just as easily' be this alternative thing if it wants to get attention. And I don't think this is always a bad thing. It only gets bad if the headline is overly editorializing, clickbait or just plain false. I don't think it is in this case.
hinkley 3y ago
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.
- FollowingTheDao 3y ago
  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/images/ijms-22-11714-g001.png 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.
- mtlmtlmtlmtl 3y ago
  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 3y ago
    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.
    - 3y ago
aatd86 3y ago
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 3y ago
  > 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 3y ago
    It isn't required for useful medicine, but it is useful for required medicine.
  - aatd86 3y ago
    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).

Lutger 3y ago

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

Broken_Hippo 3y ago

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.

deleted 3y ago
[deleted]
Lutger 3y ago
You'll be positively surprised to read the conclusion of the article then: "The findings also offer a glimmer of hope that researchers can correct course and use these new insights to design much-improved treatments for schizophrenia. Treatments that can't come soon enough." Close enough, right? Journalists know how to write headlines that make people read the article, or at least some people. They are little dramas, and if you start by giving the plot away like that, as if you just simplified a scientific paper a bit, your analytics will tell you to look for a different job soon. It is what it is. So no, it couldn't 'just as easily' be this alternative thing if it wants to get attention. And I don't think this is always a bad thing. It only gets bad if the headline is overly editorializing, clickbait or just plain false. I don't think it is in this case.

hinkley 3y ago

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.

FollowingTheDao 3y ago
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/images/ijms-22-11714-g001.png 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.
mtlmtlmtlmtl 3y ago
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 3y ago
  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.
  - 3y ago

aatd86 3y ago

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 3y ago
> 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 3y ago
  It isn't required for useful medicine, but it is useful for required medicine.
- aatd86 3y ago
  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).