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Moonlight-Moonlight

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what a random and fucked up thing to be incapable of doing. imagine being incapable of finding a place to live and staying there indefinitely. instead, imagine constantly moving from place to place, on other people's property. that's what they do in europe. they usually have caravans and set up homeless camp style settlements on private property until they get kicked off or feel their biological urge to "travel" again. they have no sense of reason and cannot be convinced out of this "lifestyle." if a random lone gypsy ends up in america (outside of the caravan), they do airbnb scams in order to squat on random people's property. they are just driven to do this endlessly.
 

$lave

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zomgoodness they didn't have a written language until the 16th century
 

Moonlight-Moonlight

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>angry about squatters
>hmm i'll watch police videos for catharsis
>search "shoplifter arrested"
>start watching this

wow these people actually have antisocial personality disorder or something. this shit is insane wtf some people really just need to be removed from society huh

now im mad about multiple things
 

Moonlight-Moonlight

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bristol myers squibb is only aiming to get it on formularies as adjunct therapy, at least for the foreseeable future. that's also what EMERGENT-3 was designed to support; it doesn't have use of other antipsychotics in its exclusion criteria. in fact, they exclude patients with early psychosis or treatment resistance. (it would probably be unethical to jump straight into using an investigational drug as monotherapy for such a serious disease even within a clinical trial, anyway, especially considering potential diminished capacity to consent)

it would be incredibly interesting and great if muscarinic antagonism is an entirely different treatment modality than D2 antagonism, but it's possible that karXT's mechanism of action is actually rooted in downstream dopaminergic changes that are impacted by changes in acetylcholine. we have yet to see if karXT has noninferiority as monotherapy, but we also don't know whether or not it exacerbates the metabolic side effects of dopaminergic antipsychotics when used as adjunct therapy.

i think the most interesting outcome would be discovering that not all schizos are the same type of schizo, with some responding better to cobenfy because they have a muscarinic etiology. i've thought a lot about this due to the existence of anticholinergic psychosis... how different does that feel from psychosis induced by stimulant use or use of antiparkinsonian drugs? this is why i'd like to try datura some day, for science... :heh:
 

Moonlight-Moonlight

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once you're used to reading clinical trial protocol documents, you start to notice how drug studies tend to be structured around the financial aspirations of their sponsor. this becomes more obscured when they write the actual paper for public consumption. in the case of karXT, it seems to me that they elected to simply exclude everyone who wasn't their target demographic of people relatively stable on some other antipsychotic already rather than do the more logical thing and pick stable use of 1 standard-of-care antipsychotic as the entire patient population, then either augment with the investigational drug or placebo. that would make the study more tightly controlled, but it would also make it so that more research would need to be done before assuming you can apply the findings to every standard-of-care antipsychotic. doing things this way, they were able to get FDA approval for general use with just 1 study.
 


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