How does genetic predisposition factor in? Is amphetamine treatment contraindicated people related to psychotic patients? If yes, when does this contraindication begin? 1st, 2nd, or 3rd degree diagnosed relatives?
1 out of 100 PERMANENT psychosis from amphetamine use is categorically impossible, especially if not counting psychosis primarily mediated by sleep deprivation. Greater frequency for psychotic events may well be the case. But "permanent" and "schizophrenia-like" psychosis are also not facially consistent descriptors. Schizophrenia is chronic and substantively degenerative, but positive symptoms are the least progressive of the three categories of symptoms. As you point out, the severity does mean 1 in 1,000 would still be very substantial. I think clearly would still be the risk:benefit in favor of treatment, but that's purely subjective. Interesting to me is the fact that TAAR agonists are increasingly described as antipsychotic in the literature, although amphetamines are more than just TAAR agonists. But since they are significant TAAR agonists, I wonder if there are both direct and rebound/withdrawal components to amphetamine psychosis, dependent on different sets of activities.
I'm not at all clear what you meant by categorically impossible. I think that the current thinking is that the dopamine overload is a much more potent trigger than TAAR agonism is a protector against psychosis. As I mention in the video, most cases of amphetamine induced psychosis seem to start while consuming the drug, and persist for days or weeks after the drug is gone, so I don't think that rebound/withdrawal are major issues here. More likely that the excess dopamine has pushed parts of the system into a new state, which some recover from and some don't, and that antipsychotic medications appear to facilitate getting out of that state.
@@DrJohnKruse Agree on every point about the mechanism. Most especially, the necessary involvement of an equilibrium change given the long-term impact from a very short-term perturbation. As for the claim, there are about 7 million patients prescribed amphetamine in the U.S. each year estimating from the Top 300. That would be 70,000 new cases of new permanent psychosis per year. Estimates for schizophrenia diagnosis vary, but typically around 1% prevalence and around 100,000 first-time diagnoses per year in the U.S. While drug-induced psychosis definitionally is not schizophrenia, it's become increasingly clear that cannabis use is correlated with later psychosis and schizophrenia diagnosis, so, presumably, individuals w/ intractable amphetamine-induced psychosis could also qualify at some point. My language was about as strong (or, perhaps, categorical) as possible, but I don't think it's in the vicinity of plausible that 70,000 people every year, less those who suffer long-term psychosis but are nevertheless prescribed amphetamine again, suffer new-onset intractable psychosis given the schizophrenia statistics overall. While I'll concede that those numbers exclude other psychotic/"schizophrenia spectrum" disorders so are an undercount, these numbers also discount all illicit-only users of amphetamine, that is, those who use it having never had a script. I'm also not aware of any evidence, but please correct me if there is, of intractable psychosis from irreversible inhibitors of MAO-B, and given phenethylamine has very similar releasing efficacy for dopamine to amphetamine, PEA accumulation along with less dopamine degradation seems like it's a pretty direct route to the same putative mechanism, unlike with pure reuptake inhibitors, but maybe there's an additional protective effect. And obviously its use in depression is rare. But I don't see how 1 in 100 is mathematically possible with psychotic disorder diagnoses rates, nor a mechanism based just on dopaminergic activity that wouldn't manifest with a wide variety of other agents, which seems to be to not be seen. Thanks for your reply. Absolutely, my intent is not to be flippant, and I agree with your observation that many probably are. It is imperative to consider the risk.
@@kenhaze5230 The 1/100 rate, as I said in the video, is what I have seen in my own practice, and I have described why that patient population is not reflective of the US. In the last few years there have been a few reports that consolidate on a figure closer to 1/600 for those using amphetamine products who develope an episode of psychosis, and the long term data on those individuals is tha about 1/5, twenty years later, are in a permanent psychotic state. So that would be 1/3000 of those who use amphetamine, or roughly 2,300 individuals a year. Among the more than 3,000,000 Americans with schizophrenia, it would be hard to detect the 23000 cases caused by amphetamines.
Dr., we appreciate all of your work and commitment, but it seems a bit strange to have your articles behind a paywall. I find it difficult to believe that you haven't been financially successful in your accomplished career, and this just seems a bit excessive. Not that we are entitled to your work, moreso that you do not wish to share it freely.
Thank you for helping me think about this in a new light. When I started writing on Medium five years ago, my understanding was that virtually everyone, of the hundreds of thousands of writers, were behind a paywall, which didn't seem that exorbitant, since $5 a month gives any reader access to everyone writing within Medium - it's not a me-specific paywall. I spend at least ten hours a week researching, writing, and editing my articles, so I was actually grateful, when, after several years, I was finally getting paid slightly more than minimum wage for those efforts. And it felt like a big step to give away access to articles that are specifically tied to my videos here - but I've posted dozens of free links. What you're suggesting is that I might actually have a much larger audience giving away everything I write for free. That makes it worth considering. Because my priority at this point is to educate and help people, rather than to make more money. But what I have seen so far is that most people treat free as an indicator that something is worthless. If someone is giving it away, it is often assumed that not much thought or effort went into it. I've also been surprised at the (so far) lack of crossover between my writing on Medium and my videos here. Despite the free links to articles. It seems that most people have a favored mode of information delivery. I intend to keep this UA-cam channel free. I've also rejected offers from several marketers to boost their products or collect referrals. But maybe I should also be considering removing advertisements from this channel. I know they are a distraction to ADHD minds. So thank you for the push to consider things from a different perspective, and it may well result in some changes in the coming months.
This channel is some of the best, clearest psychiatry and drug content on UA-cam.
Thank you for covering this (again) Dr. Kruse. This advice is very much something that I was glad to have *before* I talked to my GP.
Thank you for the consistent uploads!
Thanks!
this guy rules
Thank you so much!
How does genetic predisposition factor in? Is amphetamine treatment contraindicated people related to psychotic patients?
If yes, when does this contraindication begin? 1st, 2nd, or 3rd degree diagnosed relatives?
1 out of 100 PERMANENT psychosis from amphetamine use is categorically impossible, especially if not counting psychosis primarily mediated by sleep deprivation. Greater frequency for psychotic events may well be the case. But "permanent" and "schizophrenia-like" psychosis are also not facially consistent descriptors. Schizophrenia is chronic and substantively degenerative, but positive symptoms are the least progressive of the three categories of symptoms.
As you point out, the severity does mean 1 in 1,000 would still be very substantial. I think clearly would still be the risk:benefit in favor of treatment, but that's purely subjective.
Interesting to me is the fact that TAAR agonists are increasingly described as antipsychotic in the literature, although amphetamines are more than just TAAR agonists. But since they are significant TAAR agonists, I wonder if there are both direct and rebound/withdrawal components to amphetamine psychosis, dependent on different sets of activities.
I'm not at all clear what you meant by categorically impossible.
I think that the current thinking is that the dopamine overload is a much more potent trigger than TAAR agonism is a protector against psychosis. As I mention in the video, most cases of amphetamine induced psychosis seem to start while consuming the drug, and persist for days or weeks after the drug is gone, so I don't think that rebound/withdrawal are major issues here. More likely that the excess dopamine has pushed parts of the system into a new state, which some recover from and some don't, and that antipsychotic medications appear to facilitate getting out of that state.
@@DrJohnKruse Agree on every point about the mechanism. Most especially, the necessary involvement of an equilibrium change given the long-term impact from a very short-term perturbation.
As for the claim, there are about 7 million patients prescribed amphetamine in the U.S. each year estimating from the Top 300. That would be 70,000 new cases of new permanent psychosis per year. Estimates for schizophrenia diagnosis vary, but typically around 1% prevalence and around 100,000 first-time diagnoses per year in the U.S. While drug-induced psychosis definitionally is not schizophrenia, it's become increasingly clear that cannabis use is correlated with later psychosis and schizophrenia diagnosis, so, presumably, individuals w/ intractable amphetamine-induced psychosis could also qualify at some point. My language was about as strong (or, perhaps, categorical) as possible, but I don't think it's in the vicinity of plausible that 70,000 people every year, less those who suffer long-term psychosis but are nevertheless prescribed amphetamine again, suffer new-onset intractable psychosis given the schizophrenia statistics overall. While I'll concede that those numbers exclude other psychotic/"schizophrenia spectrum" disorders so are an undercount, these numbers also discount all illicit-only users of amphetamine, that is, those who use it having never had a script. I'm also not aware of any evidence, but please correct me if there is, of intractable psychosis from irreversible inhibitors of MAO-B, and given phenethylamine has very similar releasing efficacy for dopamine to amphetamine, PEA accumulation along with less dopamine degradation seems like it's a pretty direct route to the same putative mechanism, unlike with pure reuptake inhibitors, but maybe there's an additional protective effect. And obviously its use in depression is rare. But I don't see how 1 in 100 is mathematically possible with psychotic disorder diagnoses rates, nor a mechanism based just on dopaminergic activity that wouldn't manifest with a wide variety of other agents, which seems to be to not be seen.
Thanks for your reply. Absolutely, my intent is not to be flippant, and I agree with your observation that many probably are. It is imperative to consider the risk.
@@kenhaze5230 The 1/100 rate, as I said in the video, is what I have seen in my own practice, and I have described why that patient population is not reflective of the US. In the last few years there have been a few reports that consolidate on a figure closer to 1/600 for those using amphetamine products who develope an episode of psychosis, and the long term data on those individuals is tha about 1/5, twenty years later, are in a permanent psychotic state. So that would be 1/3000 of those who use amphetamine, or roughly 2,300 individuals a year. Among the more than 3,000,000 Americans with schizophrenia, it would be hard to detect the 23000 cases caused by amphetamines.
Dr., we appreciate all of your work and commitment, but it seems a bit strange to have your articles behind a paywall. I find it difficult to believe that you haven't been financially successful in your accomplished career, and this just seems a bit excessive. Not that we are entitled to your work, moreso that you do not wish to share it freely.
he's just trying to make a few bucks to buy a new microphone that will finally please the ADHD masses
@@richard-u8k9r Lol!
Thank you for helping me think about this in a new light. When I started writing on Medium five years ago, my understanding was that virtually everyone, of the hundreds of thousands of writers, were behind a paywall, which didn't seem that exorbitant, since $5 a month gives any reader access to everyone writing within Medium - it's not a me-specific paywall. I spend at least ten hours a week researching, writing, and editing my articles, so I was actually grateful, when, after several years, I was finally getting paid slightly more than minimum wage for those efforts. And it felt like a big step to give away access to articles that are specifically tied to my videos here - but I've posted dozens of free links.
What you're suggesting is that I might actually have a much larger audience giving away everything I write for free. That makes it worth considering. Because my priority at this point is to educate and help people, rather than to make more money. But what I have seen so far is that most people treat free as an indicator that something is worthless. If someone is giving it away, it is often assumed that not much thought or effort went into it.
I've also been surprised at the (so far) lack of crossover between my writing on Medium and my videos here. Despite the free links to articles. It seems that most people have a favored mode of information delivery.
I intend to keep this UA-cam channel free. I've also rejected offers from several marketers to boost their products or collect referrals. But maybe I should also be considering removing advertisements from this channel. I know they are a distraction to ADHD minds.
So thank you for the push to consider things from a different perspective, and it may well result in some changes in the coming months.