Welcome to the Psychofarm Podcast. This podcast is for education and entertainment. It certainly is not medical or psychiatric advice, diagnosis, or treatment. Listening does not create a doctor-patient relationship with me or Dr. Fu. If you're a patient, certainly don't change your treatment plan because of something you hear on the show. If you're a clinician, do not use this podcast as a clinical reference or substitute for your own training, judgment, thinking, and up-to-date sources.
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Good morning, Dr. Malsberg.
Good morning. How are you doing?
Oh, not too bad. You ever feel like you have to do everything at once?
I kind of feel like that at all times.
I bet that takes a toll on you. It's got some adverse effect.
Absolutely.
Well, today we're doing something that has an adverse effect on me and we're talking about a lot of medications that pretty much do everything and also have a lot of adverse effects. People ask for it. We're doing it. It's the antipsychotic tier list.
Everything everywhere all at once.
Oh, yeah. Good way to think about these medications. You know, they're classified as antipsychotics because usually of some kind of a historical or FDA approved use for the psychotic disorders. But the fact is they have such a wide range of receptor functioning across this class that it's almost a misnomer to call them antipsychotics. They treat almost many of them treat almost anything.
Pretty much part of every, whenever providers get together, we talk about how poorly named these things are. We need to call them by different names and we should use neuroscience, lingo, something, something, something. And then we just call it antipsychotics.
Yeah, exactly. That's a bit of a clinical shorthand. So shall we jump right in? Do we start with the best or the worst?
Well, first we should mention we're doing a tier list. And even though Dr. Fu pretends that he's anti-tier list and he's too cool for tier lists, you were the one who wanted to do this episode.
Did I want it or did I want what the other people interjected, rather projected into me? Did I internalize their needs?
From the tone of your text, I felt that you wanted it.
No, no. I think that's overstating things. I want to give the people what they want.
I know. There's no tone in text, Dr. Fu. All right. So, you know, it's kind of funny. I think we actually have a role reversal here. Before, you were asking me how we grade these things. Now we're doing, as you said, a medication that does a ton of different things, is for a ton of different indications. What's our metric for grading this stuff?
I think it's just going to be overall level of efficacy across both schizophrenia and bipolar disorders, not as augmenting agents, and in particular accounting for adverse effects, because again, these are very effective medications, generally speaking. But ones that have a lot of serious adverse effects. The other side of this is also if you treat enough schizophrenia and bipolar disorders, you're going to find that everyone is an individual.
And one medication that works really, really great in 90% of people may work terribly in one person. And one medication that doesn't work for anyone that you've ever used it on suddenly works beautifully in one person. So I think that that's true in other classes of medication. But it's extremely true, especially true for antipsychotics. So you have to always remember you need to be willing to change a game plan in a safe way and you have to be willing to consider alternatives.
Absolutely.
And so this, you know, we're using that, I guess just a small, you know, for the tier lists. S tier is the absolute best. And then it goes the standard A, B, Z, D, F. I don't know why S tier is the best. We've already discussed. This is of our generation. In regards to the ultimate say of what's S and what's A, I think the answer I was hoping you were going to give is everything's made up and the points don't matter for our tier list.
I mean, that's kind of true anyway. So very good. I don't know.
All right, so let's get started. So I'm going to have you decide the order and then you give it the grade and then we just chat about it.
Yeah, I think a lot of people are going to be angry about my picks here because my picks are a little divergent, I would say, from what most people would pick when they work with SMI because I think most people don't care about side effects. Most people just want maximum efficacy and ease and they want to set something that can prescribe and renew for years to come.
And I don't really do that. For good or bad. I don't know if you've read Big Stahls. He has this metabolic highway concept that if you use an antipsychotic that causes a lot of metabolic side effects, especially in a young person, you are putting them on a metabolic highway to eventually develop all kinds of morbidity and mortality risk from diabetes and high cholesterol. Cardiac disease, all that kind of thing.
So that actually what guides a lot of my use of antipsychotics.
One thing, and I guess I've been thinking about this more recently, is so I also, I trained before GLP-1s were a thing. So how I think about these meds was, or it's all in the context of a non-GLP-1 world. The GLP-1s do technically change how we should think about these meds, and it hasn't been fully integrated into psychiatry yet. I'm just putting that as a disclaimer. Yeah.
That's true. That's true. Though I also have some patients on GLP meds who haven't really lost any weight. So it's not necessarily a golden bow of psychiatry, but I do suspect there is some significant beyond metabolic effects of it. And I'm excited to see where things go in the next decade.
Yeah, definitely. And don't be afraid to be, you know, I always, when I was training, I'd always say we don't use Metformin enough with these medications. Now I'm thinking we don't use GLP-1s enough with these medications. But yeah, we'll see how things land. All right, give us our first med.
I've selected the first med, and I think it's because it's going to be controversial and there's something to talk about. It's Haldolp. Haldol goes into the S tier. This is really controversial. I think in a lot of areas, they won't use Haldol at all anymore unless it's inpatient on like a state hospital or something. I actually think this is a mistake. Why is Haldol good? First of all, it works.
It works really great. Second of all, it has basically no metabolic burden compared to the other ones in the second generations and the first generations. Not terribly sedating either, though it can be. Yes, it, generally speaking, has more risk of EPS and tardive dyskinesia, but that's sort of the trade-off that you make with these medications. You ask yourself, Do I want to be sleepy, fat, and full of metabolic syndrome?
Or do I want to be developing more targeted dyskinesia and having more akathisia? Those are the two trades that you get. Now, of course, there are always exceptions. There are people who are on clozapine, gain no weight, right? There are people who You are on high-dose Haldol forever, never get any tardive dyskinesia. But those are, of course, the rarer cases. When we are using these medications in serious mental illnesses, we need to prevent this seriously horrible outcome, and we have to accept some level of side effects.
Yeah, I would be upset if I saw Haldol and Haloperidol as an S-tier. Just as a disclaimer, these choices are, it's almost relative to what other people think in terms of how you're putting it. I do not think of it as, just because S-tier does not mean it's a first-line medication. I don't think you should be thinking about Haloperidol before a different medication. For each of these ones, I'll probably, you know, So I guess when I think about receptors and pharmacology, I try to use the pharmacology to help me remember clinical tidbits.
And I see in psychiatry oftentimes people do the reverse, where they learn the pharmacology and then apply the pharmacology to the drug independent of the clinical facts. Does that make sense? So I'm going to talk about the... For each medication, I'm going to try to give a little bit of a receptor thing that's actually linked to what I see with the medication. I think of Haldol, very potent D2 blockade, relatively little of the HAM receptors.
I call the HAM receptors... Histamine, Alpha 1, Muscarinic receptors. So the histamine has to do with the sedation, the weight gain, the Muscarinic has to do with the sedation, all the anti-Muscarinic problems. The Alpha 1 is the orthostatic hypotension. I think this medication is a very potent selective D2. Yeah. Yeah.
You know why I think Haldol gets a bad rep? Because it's old. Okay. I don't think a lot of people know this, but Haldol and Risperdal have the same chlorpromazine equivalents in terms of milligram dose. Okay. One milligram of Haldol is roughly equivalent for a D2 blockade to one milligram of Risperdal. But for some reason, no one ever starts on 5 milligrams of Risperdal. But they routinely start Haldol on 5 milligrams.
Why? It's history. It's because they used to dose Haldol to EPS or Parkinsonism and then draw it back. This is the old inpatient era. You do not need to practice this way anymore. Haldol comes in 1 milligram and 2 milligram tablets. And on top of that, then you can also raise its dose above that 8 milligram threshold for Risperdal when you need to. OK, there's a lot more flexibility here.
And I also think that the old tale of it causing depression is overblown because I have successfully used it in many cases with mood features now, and they have improved in terms of depression. But you do have to be careful because any major dopamine blockade medication can at least cause neurolepsis, you know, some apathy, emotional blunting and low motivation.
Yeah, I think, I think, tell me if I'm wrong. I think every resident has this story where the resident freaks out about like the patient's a little bit stiff or having a little bit EPS. And then the old season attending kind of tells the story of like, we used to shoot for that and then go back a little bit. So it's like, we, you know, we think of EPS as like an emergency or some of the EPSs are, but any sort of like EPS problem is an emergency.
And the old season attendings are like, this is child's play, which is not a good thing, but yeah.
Yeah. So I don't use it first line, but if patients have failed a couple ones and they have a very serious mental illness, very symptomatic suffering, and on top of that, they really don't want weight gain and sedation, try the Halidol, but treat it like Risperdal. Don't be afraid to go up to, you know, 10, 15 milligrams in very rare cases, but most of the time they will respond below eight milligrams, just like Risperdal.
Awesome. I like the, all right, Halidol, Haloperidol, nice tier. What's our next one?
Okay. Next, to annoy people again, we're going to do quetiapine. All right. Let's put it in C tier. Quetiapine goes into C tier. And it is a bit of a shame because I would say that its efficacy is at B or even A tier. It's actually really good for non-schizophrenia conditions. It has good mood efficacy. It's very effective. You can look at the meta-analyses. It's really good.
You can use it in PTSD, anxiety, depression, all that stuff, but massive weight gain, appetite increase, diabetes risk, and sedation in comparison to the actual antipsychotic benefits you're getting. So it's neither man nor beast. It's this thing where you get all the good and the bad wrapped up into one. And for me, at least, I don't think there's enough good that's making up for the bad for quetiapine.
I think you can get that using other medication combinations. People like it, though. It's easy. And a lot of people swear by it. It really changes their sleep and their nighttime in a certain way.
Yeah, it's actually funny. One of my videos, which has the clozapine, olanzapine, quetiapine video, and actually just yesterday I received the comment, you seem to have been personally victimized by quetiapine. The important thing to know for quetiapine is it's a different drug at different doses. I think one of the, probably the best video I've ever made is the Cerepyl fountain, quetiapine fountain video, which kind of talks about how to think But the gist is that at low doses, it's a sedative at 50 milligrams and below.
It's really just hitting the histamine at the 300 milligrams and below. We think about it as more of the mood symptoms. And then above 400 is when you start to get that D2 blockade. So it's really important to know that Seroquil isn't 50 milligrams of Seroquil isn't one eighth of 400 milligrams of Seroquil quetiapine. They are literally different medications at different dosages.
Yeah. If you don't know what Dr. Malzbeer is talking about, you need to go right now and watch that video. Okay. Or read the article that it was inspired by because this is such a fundamental concept that applies to almost every antipsychotic that if you don't understand that, you really don't understand how to use antipsychotics even. So please, please go and learn that. We might as well rank Serequil XR, Quetiapine XR now.
At the same time, let's put that in D tier. I think it's so silly that this medication exists. My sense is that the only reason why it exists is because when Serequil came out, we were still kind of in that camp where we thought that we needed 24-hour coverage of antipsychotics in order to have efficacy. So then they got the bright idea. Hey, instead of dosing it twice a day, let's make a 24 hour version.
Well, should you really have the sedation of Seroquel for 24 hours a day? I don't think it's a good idea. So frankly, I don't think there's any good reason to do XR. And it also blunts the benefit of Seroquel's peak early on in the night to do sleep, right? And then you're trading it off to put it in the daytime. I don't see a good reason to use it.
Correct me if you disagree.
No, no, definitely agree. I think a part of because we learn all these medications on inpatient and on inpatient, we dose a lot of our antipsychotics twice a day. A lot of people don't ever learn that after a patient leaves inpatient, the best thing to do is smush it all into, you know. One time a day dosing. So this is for especially like Risperidone. I had a lot of patients on outpatient.
They come to me and they're on BIB dosing. Push it all into one day or into one dose. It's silly to have a medication that has such adherence difficulties. The only other point with quetiapine that I want to make is in terms of where I think it has a really good role is probably bipolar 2. So quetiapine is one of the only antipsychotics that kind of covers the whole gamut of bipolar.
So it covers the depressive episodes. It covers the mania. Whether or not it helps with maintenance is a different question that this year gave me has a lot of comments to say.
But the studies say it does, you know, and I'm inclined to say it does.
So bipolar 2 is probably where I think it definitely has a role and that patients should be, we should be considering it.
Yeah, it's still just juice not worth the squeeze for me. Again, it rocks. You can see it rocks in the studies, but is it actually better in the long run than let's say lithium plus lamotrigine? I don't think so. But, you know, they don't study that kind of thing head to head. I agree, but I think you should consider it. Yes. You should consider it, but consider the side effects.
Okay. We got to do Closarill next. And politically, I have to put Closarill in S tier. I think the world would riot if I didn't do so. Okay. It's really, to me, more of an A tier, and that is because of its weight gain and the monitoring requirements.
What's that? Because you almost have to, in terms of how we're grading it, it's almost relative to how it's being used because it's being so underused.
Yeah, but it's underused for good reason. The monitoring requirements basically make it impossible to use. Also, the titration requirements similarly make it extremely hard to use because who has that amount of time to get somebody stable these days? It essentially self-selects for patients who are lower acuity. It still seems to work really well. Okay. But there are so many risks. So really, I'd like to put an A, but since it is kind of the king, you already pre-put a crown on there, you know, for good reason.
We have to put an S here. It's a matter of ordained royalty for clause rule.
Yeah, it is funny you're saying. I think we've all also gotten patients that are super high risk, super non-adherent, and then inpatient starts them on clozapine, and it's like, why did you do this? They come to you five days after discharge, and they're like, yeah, I stopped the clozapine. It's like, yeah, this is okay. That's one. I guess one important thing. So we're talking about severely underused.
It is probably our best antipsychotic. The important thing that I like that is so important to know is stopping a medication a ton of times. Substack, Substack, Substack, Psychofarm. Yeah. It's a whole bunch of different receptors. It does cause a lot of weight gain. If the patient's been off of it for more than 48 hours, you need to restart the titration. The REM requirements have gone away, so you don't need to log into the database.
That doesn't mean that the monitoring has gone away. You still need to do the monitoring, although it does loosen up for patients that might need it. With lithium, there are patients that I know need it, so I'm very lenient with regards to the monitoring
because the benefits outweigh the downsides. I guess there's a little bit more leeway for that now.
Yeah, people need to remember they took away the REMS. They didn't take away the recommendation. So technically, anytime you don't do the classical REMS monitoring, you are outside the standard of care and you're putting your license on the line. So you have to use your clinical judgment. It's a good thing. I agree that that's a good thing that they drop the REMS. But all the same, it's still you're supposed to monitor, especially for new patients on it.
Yeah. We did do an episode without Dr. Fu. Me and Roxanne did a top 10 something, things you need to know about clozapine. Only other one I'll add is make sure, you know, consider starting a bowel regimen prophylactically and ask the patients if they're pooping. That's something I want to miss.
And at least if you're not going to do that, monitor the bowel movements and the timing strictly. Okay. While we're on the topic, we should talk about, you know, clozaril at home, clozapine at home, if you know the meme. It's olanzapine, okay? For most patients where you wish you could use clozapine, well, you're We're going to have to use olanzapine. And this one goes into A tier.
If it was not for the fact that it has the most weight gain out of all the antipsychotics in the studies, way more than clozapine. It is perhaps the most effective antipsychotic out of all of these in all of my experiences. And don't be afraid, like Haldol, to dose it lower for milder cases. It comes in a 5. The pearl I always mention is that it has a unique time to peak.
The time to peak for most of the antipsychotics is two to three hours. For olanzapine, six to eight hours. So for many people, it's better to try taking this earlier in the evening. And we have some evidence to suggest that going to what the state hospital What's called heroic doses can actually be quite effective for some rare people who have very serious schizophrenia. We're talking 40 to 60 milligrams.
I will not go about 40 milligrams personally in outpatient, but I have seen That can go wrong too. I've seen people get completely zonked and neuroleptized. But I've also had the off guy who comes in on 40 of olanzapine and I'm like, that's a lot of olanzapine. Let's see if we can go down a little bit. And I move it down five milligrams to 35 and then he decompensates.
So there are some people who really benefit from high dose olanzapine.
Yeah, I totally agree. I like the take-home clozapine. I do think of olanzapine as the second best antipsychotic. The name is very similar, clozapine, olanzapine. In terms of how I think about how effective it is, Oh, yeah. Other details. So patients actually really like olanzapine. I know a lot of times we think of all medications that cause weight gain or have sexual side effects as like patients are going to hate it.
Patients do report liking it. Patients actually report clozapine as their favorite answer. So keep that in mind. It's not like the patient hates it and we like to use it. It's like the patients like to use it subjectively. It just has problems. In Katy, the olanzapine had the longest time to discontinuation. So patients would take it for nine months compared to like three and a half to six months for patients.
Yeah, probably not true, but you might as well do it for carefulness. So another detail, olanzapine and clozapine are impacted by smoking. So they're both CYP1A2 substrates. Any CYP1A2 substrates, smoking, burning leaf has the potential to induce CYP1A2. So it will decrease the levels of olanzapine and clozapine. Important to consider, patient goes inpatient, isn't smoking, then they go outpatient and all of a sudden the medication is not working as much.
Always ask if they're smoking cigarettes.
Yeah, yeah. In this case, it's even one where I might gently suggest switching to vapes, even though they're a little bit more addictive, because in the end, that probably has less burden, disease burden on their lung functioning if they're using mainstream, safer vapes. Yeah, this goes to show individualized treatment plans. Sometimes we recommend vaping. Okay, together with this, we should go ahead and throw olanzapine samidorphan into B tier.
Okay, I am not very impressed with Libalvi. That's the brand name. They threw some samidorphan on. If you look at the actual study signal, it's barely any different group to group in terms of lower weight gain. But I think there's probably some small effect. Some small effect. And I would put it above olanzapine, except for the fact that it is still on patent, extremely expensive. And I don't think the cost is worth the benefit because you still get plenty of weight gain on this one.
You still get plenty of weight gain. So it's that.
Absolutely. And I think we should be more comfortable with telling patients to consider GLP-1s. I think with the antipsychotics, I think it should be part of the treatment plan. We should be conceptualizing patients as a patient who's not taking medication due to weight gain is a failed medication. And if GLP-1s can help prevent that, then it should be a part of our treatment plans.
Of course, the problem right now is how can you afford the GLP-1 for most patients who require antipsychotic, but that's a separate matter. We won't go into that.
Yeah.
Now, while we're on the topic of adherence, while we're on the topic of medications that work, we have to rank Risperdal. And Risperdal is solidly A tier. Okay. It works great. It works really, really, really well. And comes in a lot of different forms, right? As small as 25 and as big as what, four milligrams, I think? It's very, very effective. What can I say? It's great.
But... Weight gain, sedation, orthostasis, dizziness, sexual side effects, elevated prolactin, and gynecomastia. The guys don't like that, right? So it's got a lot of side effects. I want to consider that because it has two active parts. It has the risperidone activity for the primary molecule. And then once metabolized by the liver, it becomes its active metabolite, which is a separate medication we're probably about to talk about in Vega, paliperidone.
It's kind of variable and it's half-life for people. So that's probably, in my opinion, this is a theory why some people actually need risperidone twice a day and some people don't. It's because it's just kind of a unique medication.
I do think of Risperidone as the Goldilocks medication. You kind of mentioned with the first gen and the second gen, you're either choosing a ton of weight gain or a risk of EPS and tardive dyskinesia. Now, Risperidone is that Goldilocks, not too hot, not too cold. It's got a little bit, it's got one foot in kind of both camps. So you often see on inpatient, risperidone is the first antipsychotic that's chosen on the algorithm.
And when I first started residency, I was like, why is that? We know that there's better medications. There's medications that are metabolically Well, Risperidone is that Goldilocks. It's kind of in that middle ground for all of them. So it makes it a strong choice as a first line choice. It sits near the top in regards to efficacy without all those major weight gain. But of course, there is weight gain.
The thing to keep in mind, it's for the second gen antipsychotic, the most prolactin elevating and also the most likely to cause EPS, especially when you're hitting the four milligrams and above.
I think it causes more of it even than haloperidol, but I don't know. Maybe that's just from using it more. Causes more of what? Hyperprolactinemia.
Yeah, yeah. If you have any patient that has any sort of potential hormone-related issue, menstrual changes, libido changes, changes in breast size, milk production, checker prolactin levels, It's super low threshold to check our prolactin level on these patients. Other detail about risperidone, pretty decent for OCD augmentation. They're usually using it in a lower range, like two to three milligrams. Also keep in mind- Ooh, that's not lower range.
That's mid-range. Okay. I just mean, don't go above, you know, don't go too high. Also keep in mind, some of the antipsychotics can actually worsen OCD. I think clozapine and olanzapine are the most likely. Yeah.
Yeah. So while we're on the topic, we might as well talk about paliperidone and Vega. And I would, I guess it depends on where you, okay. A lot of people only think of paliperidone as an injectable because of the popularity of in Vega Sustena and its other forms. I think I would put it at B tier otherwise, but because it comes in so many different forms and has so much utility, it has to sit up there in A tier with their speridone.
Because it's naturally less effective or potent. In a sense, then Risperidone because you're only using one instead of two molecules. But that also makes it a little bit more predictable from patient to patient in terms of response. And then on top of that, again, lots of different injectables all the way out to a six-monther. Though I do find in the three-month and six-month forms of Invega LAI that some people do need to get it a little bit earlier.
And if you look at the data for the... Serum levels of people on these LAIs, there's actually quite a lot of variation. So sometimes you do have to kind of go off book by one or two weeks. Yeah.
I guess, you know, for paliperidone, as you mentioned, it's the risperidone's active metabolite. So the name of the medication is 9-hydroxyrisperidone. So the liver does something to throw a 9-hydroxy on the risperidone. So it is risperidone without any sort of liver issues. So there's significantly less drug-drug interactions because it bypasses the liver and it's basically really clear. Yep. It is the only antipsychotic approved for schizoaffective. That's a remnant of how we read this.
No, I will say it is effective. Yes, it is effective and schizoaffective. Anyway, go on.
That has more to do with how drugs decide to go after FDA approvals. I wouldn't think of it as a special niche in schizoaffective, but it does probably work in schizoaffective. The LAIs, the long-acting injectables, Indega Sustaina is the monthly, Trinza is the three months, and then universally, everyone's favorite medication name of all time, Invega Half-Era, which is half of a year. That's right. The other detail about paliperidone is it failed FDA approval for bipolar mania.
Now, I still think of it as a medication that's effective for bipolar mania. Yeah, definitely. I think of it as it's going to be off-label, but it still has a good evidence base as an effective medication for bipolar mania. And we would use it all the time inpatient, especially the LAI, and I saw it work really well.
Oh, you know, while we're on the talk with LAI, I need a PSA here. And I hope we can highlight this in some fashion. It's going to be right in the middle of the episode. But do not trust the Invega Sustenta label saying that you do not need an oral bridge in the first month when you load. OK, you do need an oral bridge because all they're saying is that by doing the loading dose, you have a clinically significant amount of the paliperidone in the system in that first month.
A clinically significant amount is not necessarily enough to actually stabilize somebody who needs more than that clinically significant first month amount because the stabilization serum level for any LAI happens several months later. So I have seen many cases of people who were stabilized decompensate when they're switched to Invega Sustenta because of the wording of that particular instructions for Invega Sustenta. I always give A one to two week, at least three quarters bridge dose and then drop it off slowly every two weeks from there.
Because again, especially in a easily decompensating patient, you can really throw someone into a bad situation because you didn't do a oral bridge within Vega Sustenta just because you don't have to do an oral bridge. Oh, I also forgot to mention one of the reasons why I love Haldol is because it has a decanoid. It has a long acting injectable and it's a pretty dang good one with a wide range of efficacy and doses.
Where I trained, we loved not using oral bridges because we wanted to get the patient out very fast. So we would just very quickly get the LAI and get them out of there.
And I think that was more to that doesn't even make any sense. Just give them a prescription of the Risperidone and they'll take it or not.
Or you can change how you think about the medication to justify not doing that.
Okay, while we're on the topic of long-acting injectables and not adherence, there is a medication that I like to think of as an oral long-acting injectable. Okay, it's a great medication. The side effect profile is pretty dang good. But the downside is that it's just really not that efficacious. It just doesn't really work very well in the end. Now, for some people, it works enough or... All the way, and that's great.
Use it on those people. Have you thought of what I'm thinking of? It's Abilify, Aripiprazole. Aripiprazole probably has to go in B tier. I probably would have put it into A tier when I was younger, but having tried to use it a lot because of its favorable side effect profile, it's simply not efficacious enough. This is again for the serious mental illnesses. It is probably the number one augmenting agent at a low dose for depression, proper depression when added to an antidepressant, but by itself doesn't really help in bipolar depression.
Hit and miss and limited efficacy in schizophrenia and severe bipolar. Yes, it's well tolerated. Yes, it has lower risk of tardive dyskinesia. Still has some weight gain, but less. But it's just a little lackluster. But I've got 90. So if you have a patient that skips several of their doses every week but is still taking their medications several times a week, don't be afraid to use a higher dose Abilify.
Let's say they're stable on Abilify 15 in the hospital. We'll give them Abilify 30 and they take it three or four times a week. You might get somewhere closer to that. This is the kind of creativity you need to do when treating the SMI population.
I'm conflicted. You didn't give me time to answer the question, and I did the answer, but I also don't want you to ask me questions like that because then when I don't know the answer, I don't want to be pimped.
It was meant for the listener, not you, but okay, go ahead.
Yeah, so it's got a three-day half-life. Whenever you're thinking about half-life, that means steady state you have to multiply by five because it takes five half-lives to get there, so steady state takes two weeks. In terms of how I think about... Aripiprazole. The big thing to know again is it's a D2 partial agonist. Don't get too caught up in what that means. Yes, it's a D2 partial agonist, but it's super duper close to being an antagonist.
So things you need to know. It can actually lower antipsychotic induced prolactin because even though it's a partial agonist, it binds first before the other antipsychotics. We think of it, or at least everything you read says it's got minimal weight gain. We've all seen patients gain a ton of weight on aripiprazole. I do think women are affected significantly worse than men. Most of the patients that I've seen gain a ton of weight tend to be women.
Still low EPS. Now, the thing that I think we should be talking about in terms of where it should be used is, and I know you're talking mostly about schizophrenia and the psychotic illnesses, but MDD augmentation. It is the most studied antipsychotic for MDD augmentation. Again, remember augmentation. So it should be added on top of another medication in general. The evidence sweet spot is the two to five milligrams.
So you shouldn't be kind of lasting it up to the higher doses.
Don't go above five.
It's probably, I feel like a lot of antipsychotics I do tend to dose at night. Aripiprazole is one of those medications that I'm more likely to dose in the morning because stimulation can outweigh sedation for a lot of patients.
Yes, for the augmentation. I would say that if you're not using Abilify Aripiprazole for the augmentation, if you're using it for bipolar maintenance or for a schizophrenia-type disorder, well, because of its partial agonist process, You should probably start around 15 and no lower than 10 milligrams. I've seen people respond with lower, but remember, what does that partial agonist mean? It basically means that about 20% of the dopamine receptors that it is bound to is not blocking.
It is maybe stimulating. Okay, that's what that means. So if you want to treat more severe illness, you will have to go higher on the dose. A lot of people like to add this to Clozapine because the receptor profile is so different. I guess that's fine. I've never really seen that work suitably. A lot of people then like to add it to other antipsychotics. Beware. I really hate the practice of adding it to Haldol.
You're basically making the medications fight each other because it binds so tightly to dopamine receptor that it essentially counteracts a lot of other antipsychotics. So just, you know, if it's not working, use a different antipsychotic. That's what I say.
Yeah, absolutely. All right. Our next one, should we do Brexpiprazole next or?
Yeah, yeah. Brexpiprazole or Rexulti is essentially Abilify, but harder to dose because it comes in smaller milligram increments, in my opinion, and way more expensive. So I'm going to put it into D tier. Until the price changes, it is in D tier. Just one of those things where there's no practical use case because there is something essentially equivalent that costs a lot less and has easier use.
Yeah, in terms of how I think about it, so the D2 partial agonists are ABC, aripiprazole, brexpiprazole, cariprazine, the pips and the rips. It's aripiprazole with the volume turned down a little bit. So it's got a little bit less intrinsic activity than aripiprazole. So that's how you kind of think about it. It's a little bit lighter than aripiprazole, less D2 activity, probably lower metabolic and EPS burden, probably less akathisia.
But none of these things, it's not like it is There is still some of these things. Very similar. It's potentially an MD, major depression adjunct. It's not a boot stabilizer. It has been studied with PTSD. So it was studied with Zoloft. It had one of two positive trials, but the FDA rejected it probably because of the antipsychotic. Again, another medication with a long half-life. You mentioned the adipiprazole had the long half-life.
I'm in agreement that it is a medication I very rarely reach for. Once it's generic, it's very possible I'll feel very differently. But until those medications are generic, having a patient pay a ton of money for something that you can probably get the same thing, maybe a little bit better is silly.
Yep. Yep. Getting now into things that work. I am going to do another fairly controversial thing here. I'm putting lurasidone, latuda, in S tier. This is one of my...
I'll put that. Should we do cariprazine just because, just finish out the partial agonists?
Oh. Okay. Put it back then. Put lurasidone back and we'll do cariprazine first.
Okay.
Where do you put Periprazine? Give it a B. Give it a B. That's nice. I kind of like Raylar, Curvies. I was more excited about it because, again, I'm always excited about an antipsychotic that has efficacy for mood, bipolar depression, and doesn't have a lot of weight gain because most of the ones that have efficacy for bipolar depression, even if they're not labeled as such, such as Risperol, have a lot of side effects.
Vrelor tends to have a nicer side effect profile, but it's an awkward medication. First of all, still on patent, very, very expensive, exceedingly so. Second of all, Just like Abilify, not very effective in the end for mania and psychosis, even if it seems to have some good effect in some people on mood. Weird, because it has two, count them, two active metabolites, so it takes anywhere from four to eight weeks at one dose to reach its maximum efficacy.
That's strange, right? Yet, for some reason, the studies did not exact So not effective enough, but well tolerated and effective in some people, but too expensive. I don't know if I really put it higher if it was not expensive. It's just not that effective, but pretty good.
Yeah. In terms of how I think about it, so it does, it is a D3 partial agonist. So A, B, C, Aripiprazole, Brexpiprazole, and Criprazine are the D2 partial agonists. Criprazine has D3 partial agonism. For some reason, the D3, even though I have no idea what D3 actually does, helps you remember it might be helpful for negative symptoms. So in negative symptoms of schizophrenia, there was one manufacturer-sponsored trial.
It beat Risperidone on negative symptoms. It's not going to be a It does have good efficacy in bipolar depression. Probably not as good as trazodone or quetiapine, but it is one of the ones that I consider, that I think of when I think of bipolar depression. Similar to the other ABCs that we talked about, really long half-life, as you mentioned. So yeah, decent. I think bipolar is where you really start to think about it because it covers the depression.
It does have evidence in mania and mixed. I think you said, you know, whatever you said. And it is potentially a unipolar depression adjunct. Again, I still use Aripiprazole first before then.
Yeah. So let's put Latuda on the board. I'm putting it into S-Class. This, I think, is a very underrated medication. Is it as effective as Haldol and claspine? No. But in my experience, if it doesn't cause you horrible akthesia, and it is the highest risk for that, if it doesn't cause that, then it's a great medication. Most people can eat 350 calories with dinner and take trazodone.
And it's hitting both marks. I think people underrate trazodone for its use in schizophrenia because of how much they push to bipolar depression. I think most people aren't aware that it probably is effective in mania. But, you know, you have to give a sleeper because of the akathisia. That's my opinion. We can quibble about the studies in the comments if you'd like. But it's a good medication.
It doesn't have much side effects. And you can give it up to 160 milligrams all at once. And that depends on the person. But, you know, should it be in S class, I almost want to do S minus. I almost want to do S minus because if you have anybody who gets fluctuating appetite because of their mood disorder or psychosis, then it becomes a no go because they're just going to intermittently decompensate if they start eating less dinner and then they'll stop taking the medication at all or they'll develop all these destabilizing symptoms.
So it's only good for people who are really steady eaters.
Yeah, I actually agree. I think it should be an S tier. I feel like you were the one who taught me that it works in acute mania. So I feel like in terms of when you just kind of read the studies and books, you do think of it as like, oh, it doesn't work in acute mania. The truth is, it's a really great medication, especially in bipolar.
It just was never tested in acute mania.
Yeah, I think they wanted to kind of sell it as an antidepressant, so they didn't want to go down that road. Yeah, bipolar antidepressant.
Now, as you mentioned, needs to be taken with 350 calories or else the patient will get half the dose. It is something you actually do need to talk to patients about. It is metabolically pretty clean. I have had patients who have been on it and have had minimal weight gain. Minimal QTC prolongation, low prolactin. The little receptor quirk that I think about is it's got a pro-cognitive signal.
I think that's kind of nonsense. The stalls, in terms of how they think about it, is they give you a receptor and then give it like it's all good or all bad receptors. So the 5-HT7, we think of that as like the cognitive receptor. That's a terrible way to think about it. It's not how medicine works. And even the neuropsych testing, it wasn't actually, or the cognitive advantage, it wasn't neuropsych testing.
It was just one of the pan subscales for thought organization. Not this like, it's not going to make you brilliant. But I do see it does have less of that cognitive dulling that I see with a lot of the other antipsychotics.
And there's at least one study showing relative safety in pregnancy. So that's a nice thing to have with trazodone. While we're on it, I believe other ones that are generally accepted in pregnancy that you can see here on the board include Haldol, Olanzapine, and Quetiapine. You know, those are options too.
All right. What's our next medication?
Well, we have to talk about trazodone's older brother, Zaprazodone. This is Giadon. It works, but doesn't really work for mood. And it has much greater calorie requirement. I'd put it in C tier. It works. It works. Quite flattening. Lots of dopamine blockade. Not much help for mood. But it's not a bad choice. The QTC prolongation should not scare you. It's basically clinically insignificant. If you want to be extra careful, go ahead and get your...
You know, EKGs and whatnot, but, you know, it's not significant. And the main drawback is actually the 500 calorie absorption requirement that not everyone can routinely do that up to twice a day, which you might need on zaprazodone compared to the trazodone.
Yeah. So the Ziprasidone is 500 calories. Lurasidone is 350 calories. I feel like that's a big difference. I feel like that's the difference between a full meal and you could get away with a snack on the Lurasidone. Yep. So Ziprasidone has strong 5-HT2. That may be why there's QTC prolongation. Overblown, but it's still real. There are studies that it works for acute agitation. And some people say it's underused for acute agitation.
So I guess IM suprazodone helps calm the patient without like flattening them. So, you know, theoretically, when you're using IM medication, I think we should do an episode on acute agitation because that makes me sound like we're just trying to zog patients, but yeah.
Yeah, no, it's used quite often around here. People like it for IN for agitation. It works fine. You know, I think people have to understand that the main effect in giving a PRN for agitation, I think, is the social component and the sedative, not the antipsychotic. So whether you want to use zaprazodone or haloperidol, haloperidol is about, you know, equal to me.
I want to talk. Other last things? I'll just be quick. I've already mentioned this, but we do think of it as one of the more metabolically better medications, lower on weight gain and diabetes. Geodon, the name is down to earth, eliciting just nice feelings. And then not good evidence in bipolar depression, but you mentioned that.
Yeah, I find that I really have to struggle with the depression component for my bipolar patients, the serious bipolar and schizoaffectives who get put on geodon. So I don't love it. If they can handle the razodone, I'd do that any day of the week over the zaprazodone. So while we're on the subject of big brothers of lurasidone, we should talk about buspirone, which is not an antipsychotic, but they wanted to make it an antipsychotic originally.
Since this is the antipsychotic tier list, I would put it in D tier, but not F tier. I'll explain why in a second. I'll explain why in a second. Okay, so a lot of people don't necessarily know this. B-sperm was originally investigated as an antipsychotic, originally investigated as an antipsychotic, and it is an antipsychotic at very high doses, something like 200 or 300 milligrams. But because it took such a high dose, I believe trazodone is a combination molecule.
One half based on the structure of Geodon, Zaprazadone, and the other half based on the structure of Buspirone, an Aziparone class medication. Okay. Azaparone class medications are a bit new and emerging. As you know, we now have, what is it, Exua? But why am I not putting that one on? It has minimal D2 blockade. Why am I putting buspirone on? Because it kind of has some D2 blockade at high doses.
And I am willing to take it up to 90 milligrams or so, but you have to look out for the sedation orthostasis. And I actually think it's quite a good augmenting agent in the direct treatment Of schizophrenia spectrum disorders and bipolar disorders for the people who can tolerate it. You're basically kind of doing a synthetic second generation style receptor profile by adding buspirone to something that has D2 blockade.
And then by pushing the dose, it's almost a second antipsychotic.
Buspirone is Dr. Fu's baby. Now, I've mentioned this before. All experts, they essentially, what you always see is it always boils down to one, you know, like this year gave me, it's like all roads lead to lithium. Whenever you have an ADHD expert, it's like all roads lead to Adderall. For Dr. Fu, all roads lead to buspirone.
No, I used to hate buspirone. It's just I neglected it too long and now I love it.
Yeah, I think you made it popular again.
And then, so for that note, we should add something that I barely know about because it helps us think more about buspirone and maybe someday we'll get it. It's called perospirone. That we're going to put in need more experience. This is a Japanese azaparone. It was derived from buspirone and it is affected in schizophrenia, unlike buspirone, and they use it. I would love to know what that's like, you know, because I suspect that would have pretty good receptor profile for efficacy, lower weight gain and appetite increase, and not too much good tolerability, basically.
But who knows? I haven't used it. I won't be able to. It's in Japan. Big in Japan.
I had no idea what it was, but a little Japanese medication. All right. What's our next one?
Returning... I just saw a big green streak go across the... Well, anyway. Okay. I'm seeing things. Okay. Going back to things that work and we have access to. Acentipine. Where should I put that? Probably B-class. Acentipine. B-class.
For me, it's...
This is a... Saffiris. This is an underrated medication. Its actual efficacy might even reach that of the A class or at least somewhere between the B and A class. But it's a lot of people just can't tolerate the horrible black cherry flavor and the numbing of the Because it's the only sublingually absorbed antipsychotic that we have here. The oral dissolving tablets and films are not sublingual. They simply turn into a liquid in the mouth and then you still have to swallow it.
Whereas with Saffiris, if you swallow that, you wouldn't get any. Mm-hmm. Tasty. It also has decent amount of weight gain anyway. So if you're going to be getting that weight gain and sedation from a centipine, why not use Risperdal? I think is what most people think.
And I can't argue with that.
We want to hear about your most difficult, confusing or challenging cases. Obviously, we can't give clinical supervision over a podcast, but especially when they're de-identified, we do think we can learn together with these cases and reviewing them in detail.
Yeah, definitely. If it's on the community forum, we'll definitely get it. That's just on the farm and then you hit the community. Or you can send an email. Just make sure wherever you post it, it's de-identified.
You know, of course, de-identified and for learning only, send us your most difficult cases. I'd like to hear about them.
Awesome. And I'll also just mention that this month we're doing a book club and we'll be having a discussion on it at the end of the month. I think this month we're doing the psychoeducation for bipolar disorder.
So head on over to the forum and start participating.
Yeah, I haven't used acetapine, so I don't know much about it. I do know it hits a ton of the serotonin receptors, 5-HT2C, 2A, 5-HT7. It has essentially no muscarinic affinity, so that's a nice little plus on the medication. H1, it blocks a lot of H1, so sedation and weight gain makes sense. And I think a lot of alpha blockade as well.
So now let's go to some new and expensive stuff that people might be wondering about. Let's talk about Kapilida. The manufacturer is going to hate me for this. Put it in the F tier. Oh, boy. This is Lumeteperone. Lumeteperone. I don't say it. I just say Kapilaida. It's a lot shorter. Sorry for the international listeners. I kind of hate this medication. Why do I hate this medication?
Well, it's because it doesn't come enough doses. They just kind of said, oh, there's one dose and it works. Great. Well, you know, life doesn't work that way. And that makes things really annoying. Okay, second of all, the thing that they thought was awesome for it, I actually hate about it. I know it's approved for bipolar depression, but why it works in bipolar depression is that it has cert activity.
Okay, so it's basically an SRI that's been combined with an antipsychotic. Very clever, you know, pharmacologically, but in my opinion, causes too much agitation and cycling in true bipolars. So I would, and it's expensive and on patent. Once it's off patent, I might reach for this for patients who have schizoaffective disorder depressive type and only want to take one medication. That is where I think it probably has the most indication.
But in most cases, you're better off using other combinations. So I don't like this medication. I don't think it's very effective for psychosis either. And it's just, you can't separate the actions. So that's annoying.
Yeah, in terms of how I think about lumateperone, so its affinity for 5HT2A is 60-fold its affinity for D2, so very strong on the SGA portion. As you mentioned, there's There's, you know, 42 milligrams dose, no titrating. Sounds like a blessing, but it's really a curse. You mentioned it hits SIRT again, so that when we say SIRT, we're saying it's like a serotonin reuptake inhibitor. Very little H1, so, you know, metabolically a very clean medication.
I think that's all the pearls I got. I've never
used it. Now for Eloperidone Fanapt, this unfortunately goes into needs more experience. I have no doubt it works. I have not had really much opportunity to use it because it's not really on formulary in my area. I've only run into a couple of patients who are already on it. I would anticipate it's something like the other dones and it works. It doesn't have LAI. I don't see a reason to use it.
I don't see a reason to use it when Risperdal exists and so does Invega, but that's just me. Have you had much experience of this one?
I have not, but I've gotten a lecture on Fanatural Illoperidone. I do think of it as the alpha-1 antipsychotic. Now, my understanding, so it has very strong alpha-1 blockade and all the problems that come along with that with regards to orthostatic hypotension. Now, it does have D2, D3 antagonism. Now, the thing that the lecturer was saying that was the really big thing is, I guess, no akathisia.
So, it is a good medication for a patient that does well on similar medications, but it gets akathisia. So, yeah, that's kind of the gist with iloperidone.
On the topic of expensive stuff that we hardly use, that doesn't seem to work better than other alternatives necessarily, we should talk about Pimavanserin, Nuplazid. I have actually used this a few times. I would throw this one into D class, D as in dog, because it kind of works, but it doesn't work a whole lot. It's got that really niche use where you want to use it in patients who can't tolerate D2 blockade.
I never saw full remission of symptoms, but of course that's par for the course when it comes to psychosis associated with a neurocognitive disorder. Once it's off patent, I could see this as a nice addition for double antipsychotic choices similar to buspirone, but for now it's too niche and we don't have enough experience with it and it probably won't work on most people with psychosis.
Yeah. So Pima Vansarin, it's a 5-HT2A inverse agonist. So you get to feel very smart when you use it. Who knows what that means? No meaningful D2 blockade. So it is the antipsychotic without D2. And it was the first one. And then I guess we'll talk about another one soon.
Yeah. Parkinson's friendly. A lie. Oh, what? What's that?
Parkinson's friendly medication.
Yes.
Yes.
While we're on the topic of expensive things that don't necessarily work so well, we have to talk about CoBenphy. Lots of money going into selling CoBenphy right now. This is Xanomalintropsyum?
Am I saying that right? Yeah.
Yeah, F. Sorry, folks. I'm putting an F. I have not seen this work at all. At all. Okay. A lot of people are trying to use it kind of as a second antipsychotic because it's got a totally different mechanism. First of all, when it's tolerated, I don't see it really making much of a dent. And second of all, when it's making a minor dent, it's completely intolerable.
Okay. It's just a mechanism that people can't seem to tolerate. Even with the added molecule to make it more tolerable, people are just getting too much nausea. Sorry.
You like it better than F? So it's a very exciting medication. D2 has kind of been the mainstay of all of our antipsychotics. And then we got everyone super excited about this medication that doesn't have a D2 blockade, not going to have any of the EPS, not have any of the movement problems. But I mean, I have the exact same experience as you do. No one can tolerate it.
But just in terms of how we think about it, it's a muscarinic agonist. So it's an M1 and M4 receptors. The xanamaline activates the M1, M4. The trospium is not for the symptoms. So it just blocks the peripheral muscarinic effects so that theoretically there's less problems. But the truth is there are just muscarinic problems. The big thing is just the GI tolerability. Patients just have a tough time tolerating it.
Yeah. It's a shame. It's a shame. Okay. Now for sort of more random stuff. We've done all the big dogs. Let's talk about add a mood stabilizer. This is A class. This is A class. It would be S class except for the fact is there are some people that don't seem to have any bipolarity at all. With a schizophrenia and then it's pointless. Mood stabilizer is obviously first line for anyone with straight bipolar disorder.
But I would go as far as to say that if you have any schizophrenia spectrum disorder and you have any hint of mood problems on either pole, add a mood stabilizer. If it's agitation, probably try Depakote first along with impulsivity. That may help. And if it's anything else, lithium, lithium, lithium. And if it's depression, don't be afraid to do, again, lithium or lamotrigine. We just don't have a way to truly classify this group of patients as well as we'd like.
And you will find that augmentation, even in people who primarily have psychotic symptoms, can help those psychotic symptoms, and especially the sleep. So don't be afraid to add a mood stabilizer to your existing antipsychotic regimen, maybe even before and probably even before you add a second antipsychotic, if there are prominent mood features.
Yeah, definitely before a second antipsychotic. But I agree. A tier for adding a boot stabilizer.
Yeah. Chlorpromazine, the classic. Thorazine, the first antipsychotic we've ever had.
Started it all off.
Yeah. I hate that child psychiatrists are so comfortable around here giving this to children because it's been tested because it's genuinely an awful medication in terms of side profile. Okay. And you don't even get that much D2 blockade until you get to higher doses where it has intolerable side effects. And then for some reason, just because we have the studies, they go like, yeah, we should give this to kids.
It's crazy to me. It's crazy to me. I really think it's a sign of being way too quote-unquote evidence-based where you just ignore knowledge because someone did research on it before. Terrible idea in my opinion, but that's my soapbox. Works though. C tier? C tier?
I can't deny that.
Really? You think it's that bad? You're going to put it below C?
Yeah, I'd probably put D-tier. I've had the same experience. You always get the one resident who thinks he's a fucking whippersnapper, read a few trials, and it's like, oh, we should do chlorpromazine for, I mean, especially acute agitation. And then it just destroys the patient. It just causes so much problems. Yeah.
I guess it's almost D tier. Okay, fine. You've talked me into it. Put it in D tier. It's just because I've been reserving D and below for stuff that actually doesn't work. And I know that Thorazine works, but I also know that if Thorazine works, something else will too. Okay. And it will be more... I don't think I've ever kept anyone on chlorpromazine as outpatient, to be honest with you.
And I don't think any of my patients have ever kept themselves on chlorpromazine as outpatient either. It's just so poorly tolerated. But does it work? Yes, it works. I feel like CL psychiatrists love loxapine.
That's not really how it works. It's better to think of it as the first-gen antipsychotics have more movement problems because chlorpromazine does hit the ham receptors. So it does have histaminergic alpha-1 and muscarinic problems. The reason why we call it first-gen is because it does also cause EPS. It does cause high risk of tardive dyskinesia. Other little details about chlorpromazine, it works for intractable hiccups. And it's a really good anti-medic, but don't use it for that.
Which is what it was originally used for. So I want to dispute the second generation that has less EPS and TD claim. I know that's what the signal is in the research, but first of all, schizophrenia has its own rate of movement disorders, okay, without antipsychotic use. If you look at pre-antipsychotic studies, they were already developing tardive dyskinesia anyway. Yes, it's probable that using the antipsychotics increases the risk and rate of tardive dyskinesia, but I think the reason why we think second generations have less of it is because we use lower doses of the second generations, and the patients were on the second generations for less time than the first generations, both reasons.
But then if you're saying that, then for promazine would be atypical. Yes, I consider chlorpromazine an atypical antipsychotic, even though it's historically not. If you look at the receptor profile, that's pretty much how it works, right? It's just a matter of history, but we're splitting hairs now.
Yeah, yeah. Okay, let's move on.
So loxapine, loxapine, let's put it in C tier. I feel like there's just some nerds in psychiatry who get super excited by loxapine because the receptor profile is supposedly very similar to clozapine. I haven't seen it work very well. I feel like it does work, but it seems to cause too many side effects again, like fopromazine. It's like if you want 60% the efficacy of Clozaryl without the blood draws, but a lot of urinary incontinence and retention give loxapine.
That's the experience I have with it, but maybe I'm biased.
All right, let's keep moving quick because we're
over the hour mark. Finally, other weird first generation antipsychotics. Well, there's prolixin or flufenazine. Okay, this goes into B tier. Maybe, no, C tier. Let's do C tier.
Okay, why?
Because I don't see any reason to use this if we have haloperidol. I mean, maybe if you're allergic to haloperidol and you're not to flufenazine, but they're roughly equivalent in their efficacy. The long-acting injectable for flufenazine is really only supposed to last one to two weeks and is not very practical. So it's harder to dose and administer than haloperidol and it's not really any better. So solidly C tier, but very solid.
I don't think they're pretending. They just had bad EPS before. That's not very nice.
Just give some diphenhydramine.
Okay, anyway, next we are labeling this as perfenazine, aka trilophon, but I want you to also think of thioritazine, melaril, and trifluoparazine, stelazine. These are kind of the miscellaneous first generations that got forgotten. You might not be able to get it in your area, depending on where you are. These go into A tier, B tier, B tier, sorry, B tier. I'm putting these in the B tier and that's actually because I kind of think we should encourage them to be used a little bit more because they are more atypical than you think.
They're not atypical all the way, but they're more atypical than you think. They do have problems with weight gain and appetite increase. And there's nothing wrong with that. And we are wrongfully not considering our full set of medication options simply because they're not mentioned, talked about, or marketed.
Yeah, I'm only going to talk about perfenazine because I don't know as much as the other ones. One of our attendings used a ton of perfenazine and then anyone who was his supervisee continued to use a ton of perfenazine. What's important to know is when they I agree, it is a lot more second gen than we think of. So you get less of the EPS and the akathisia of haloperidol or the flufenazine, which are the high-potency first-gen antipsychotics.
Metabolic, be a little bit cleaner. Minimal weight gain, but still, you do get the moderate EPS risk. Actually, surprisingly decent at negative symptoms. I know, I feel like, if anything, we're kind of saying that the line between first gen and second gen medications is very blurry. Historically, we think of the second gen as better at the negative symptoms, but we do have a first gen that's pretty decent at it.
Wanted to give an honorable mention here to Droperidol, which goes into need more experience. Emergency room physicians seem to love this medication. I suspect it pretty much works like Haloperidol, but probably has some different properties that we would find useful. But unfortunately, they don't make a version of this that we can really give as outpatient orally. So we can't use it, unfortunately. And similarly, AmiSoulPride goes into needs more experience.
I believe this is really popular and good and available internationally, but not available in the United States again. So unfortunately, we can't comment.
Yeah, so droperidol is one of those things like you read about it and it's like it just seems like the perfect medication. The studies, there's a bunch of papers put out for like how to deal better with agitation and they basically say like never use haloperidol. Droperidol is the greatest thing in the world. It's the Project Beta Best Practices in Evaluation and Treatment of Agitation. It is one of these things where it's like this dream medication that no one has access to and no one uses.
Yeah, it's unfortunate. Okay. Well, I don't know if there's anything we forgot or that people want it covered. Please mention in the comments if that's the case. You know, it can be covered in sort of our Q&A version of things behind the subscribers portion. And I want to hear, please email in about your difficult cases. That's something that I think we might have mentioned before, but it's kind of a pilot for maybe a future feature.
But of course, de-identify anything you email us about. Absolutely. All right. I'll catch you later. All right. Until next time.
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