So Dr. Fu called me this weekend in tears about how few people are leaving reviews for our podcast. Do you remember that?
Yeah, that was a rough time. Please like, subscribe, share, comment, et cetera, et cetera.
No, your generic comments, it's not working. Give me the passion that you gave me on Friday night at 4 m.
I think it's not working because no one listens to the end of a 50-minute podcast. You can probably say this at the front.
All right. How we doing, Dr. Phu? Hey, Dr. Malzberg. How's it going? It's getting cold. You notice that people are a little, people are getting the winter blues.
I think we're in so different areas of the country that that's not what I'm seeing. It's actually warming up over here. Are you jealous?
I'm very jealous. I could see it in friends and family. Everyone's, everyone needs their behavioral activation to the max.
Oh boy. Yeah. You know, that's why I'm not on the East coast anymore. Uh, By the way, uh, I can hear, I don't know if you can hear a lawnmower in the background, another sign of how it's warming up around here. Uh, but hopefully that doesn't make it onto the podcast. So what are we talking about today?
That's nice. Cause if you outside my window is ambulances, so that's tells us the difference in location. Uh, so today we're talking about medications for schizophrenia. Um, Antipsychotics, but not entirely, just in regards to using antipsychotics for psychosis.
Okay. So we'll focus on antipsychotic choice, I think.
Yeah, exactly. So I'll start with some questions to get us started. First one is super simple, but actually not. What sort of factors guide which antipsychotic you choose?
So this is a neglected area, I think. I think that most... community clinicians are using antipsychotics mostly based on familiarity. And if you go off of familiarity, you're also going to, well, sorry, let me give a little credit. Familiarity and perceived efficacy. And if you work off of familiarity and perceived efficacy as your primary guidelines for what you pick, most people are going to pick Risperdal Zyprexa.
Hell. Because this is what we use on inpatient units, that's what we're trained with in the first two years, but I want to say strongly that this is not a good approach, that you're limiting your own experiences if that's what you stick to, and that patients won't stand the medications as well, where if they do, they're going to have a lot of side effects. These are good medications, but...
Long term, they cause problems. And, you know, this is a Steven Stahl idea. So what I would say is that please, please consider first the metabolic side effects when you pick your antipsychotics. Rather than what works or what doesn't, try to spare your patients the weight gain, cholesterol problems, diabetes.
Yeah. Now, something you bring up that is funny is, yeah, on the hospital I trained at, every single patient got started on Risperdal. There was zero. If you chose a different antipsychotic, you would get a message saying, what are you doing? You had to do Risperdal. It didn't matter what they failed in the past. It didn't matter if it was their first time. They would just be getting put on Risperdal.
And it's funny. I think you mentioned it's like the Stephen Stahl approach. There's like two different approaches. There's like everyone should get core medications. And then there's the Stahl approach, which is patient selection and optimizing for their receptor patient profile. And sometimes you can go too far in that direction in that direction. it feels like it's got a pharma bent that like, you know, you need their perfect medication for the perfect lock and perfect key.
And I think that there's a middle ground there between having your core medications and, and patient considerations.
Yeah. I mean, Stahl is a pharma guy and a researcher. He likes to theory craft, you know, if you look at sort of some of his early, he used to have a kind of a recurring thing. I think it might've been CNS spectrums. where there were short articles that just kind of explored theories of psychopharmacology. Really interesting reads, if you can find them. They're, I think, a little hard to find.
But let me say this. When I talk about tailoring antipsychotics to the patient, I don't mean the theory crafting that goes along, you know, certain receptors. He definitely does that. And I don't mean anything except for in big stalls. There is in the latest additions, a big page that shows you, I think it's called the metabolic highway. Okay. This is a really important concept. If you keep your patients on a weight gain, second generation or first generation, without thinking and trying other things, at least you are putting them on a highway to heart disease, diabetes, and over sedation in the long term.
So please remember that. I think it's the best thing to come out of stalls other than this robust research and it's all that data that we can rely on.
Yeah, I do want to provide a counterpoint because I think this is going to be a bit of a back and forth. But I'll wait until later on the podcast to get my counterpoint to always making sure you're not on the most metabolically – I don't think you should wait. I think we should get into it. Okay. Well, first let's name the medications. Let's talk about, let's give a little bit of education in regards to which ones are metabolically concerning, which ones are less.
And then I'll give my counter anecdote too.
Okay, sure. Damn it. I really got to mute the microphone. Okay. So obviously the best way to consider whether something is weight gaining or not for a patient is is checking their weight so you know for the telehealth people out there you can at least ask the patient to weigh themselves on a regular basis and self-report don't forget to weigh your patients now if you want to be really gold standard you're going to do waist circumference but you know how many docs out there are actually doing that so obviously probably beyond being considerate about side effects the next thing to think about is that side effects and efficacy in antipsychotic treatment is very individual.
There are large trends, but it's still ultimately individual. I've had patients with high doses of Zyprexa, for example, no waking. I've had patients on low doses of Abilify, for example, tons of waking. You just have to look at the individual patient and make decisions based on that.
Yeah.
So while you should, oh, go on.
Let's talk about the patterns. I had five clozapine patients when I was a resident. They were all rail thin, all under 150-pound males. Abilify is supposed to be one of the more weight-neutral ones. I've had patients literally just blow up on Abilify. So, yeah, the point here is individual patients have different experiences with the medications. And then the second point is, though, that there are patterns and expectations with certain medications.
I think you're about to go into those.
Yeah. So, you know, for a real accurate accounting of which ones are associated with weight gain the most, there are plenty of handy charts out there up to date, et cetera, et cetera, where they summarize the research. Keep in mind that it's observation. That's why we have to pay attention to individual effects. I think it's probably faster to name the medications that seem to be both the most commonly available and most weight sparing.
And probably the number one would be Haldol. Okay. I don't know if I've even seen Wake In on Haldol. meaningfully once but it's a first generation antipsychotic i wouldn't be reaching for it first probably the main one i reached for first due to both cost availability and tolerability reasons is Abilify i know a lot of people don't like Abilify they don't trust Abilify they don't think it works well keep in mind that there's some theory that for Abilify it may work better in people who have a more non-disturbed dopamine system meaning earlier in the disease course or not too much long-term stimulant use.
Abilify is a decent choice that still causes weight gain. You do see that in the data. It's at least decent. After that, Latuda, Giadon are probably the best ones to go to in terms of not having much weight gain. and second generation. Raylar, relatively new. I have not seen much weight gain on that either. And I believe there are a few other new second generations that have limited weight gain, but that's probably the top of the list for me.
Any other ones that come to mind for you?
Well, yeah. And one thing that I think might be helpful is teaching people how to think about this. And a good starting approach is, you know, Stahl has the Pines, the Dones, two Pips, and a Rip. And then there's other actually new ones. But the gist is that look at the last, you know, the last four letters of the name of the medication. So if it has Pine, it's in the Pine class.
If it has Don, it's in the Don class. If it's Piperip, it's Aripiprazole, Cariprazine. The gist there is that the pines are, which they were thinking, olanzapine, clozapine, quetiapine, by far the most metabolic medications we have. Then the dones have more variants. Risperidone in the middle and trazodone and zaprazodone are less likely. But the dones are less likely to cause weight gain than the pines. And the pips and the rips are more less likely to cause weight gain.
Okay. I have a meta-analysis that has the order of the meds. It doesn't have the new ones, but I want to just read the order from most to least likely to cause weight gain. Olanzapine, number one. That shows up every single time. That'll be young. Oh, yeah. That's the big boy. Clozapine number two, then iloperidone, thorazine, quetiapine, risperidone, paliperidone, aripiprazole, trazodone, zaprazodone, and haloperidol. So the top three that were commonly used are olanzapine, clozapine, and quetiapine.
The bottom three on this list are zaprazodone, trazodone, and haloperidol. And Abilify is also the bottom. Yeah.
So you can see there, I kind of draw the line starting with Abilify. Abilify, while still having his weight gain, reasonably less of the proportion than most people. But you can see I'm pretty aggressive. I do not want to try anything above Abilify unless I really have to.
Yeah, and then my little, and I guess my brain, I haven't thought about this now, at the top are the pines, olanzapine, clozapine, quetiapine, risperidone's in the middle, and then the other ones are below risperidone. It's kind of how I categorize it in my head.
Though I think we should say we don't fully understand why some seem to cause a lot of weight gain, some seem to cause a lot in some people. You know, there's theory about it, dopamine stuff, histamine stuff, but if you drill too far into the details, it doesn't necessarily pan out. So I still say it's useful to conceptualize this hierarchy based on the subtype of the antipsychotic, but rely on the data and pay close attention to your individual patients.
Yeah, individual patients, huge. And don't tell patients if you're starting Abilify that they're not going to have weight gain because it's on the lower end. You will run into problems. Your patient will not trust you. I do seem to notice that I think females have a much more higher propensity to gain weight on these medications. I don't know if you've also seen that.
You know, I think... this makes me want to give kind of an aside. Weight gain and medications, psychiatric medications, kind of a spotty, shaky area. What I would mention is, let's take a look at antidepressants, for example, right? Many antidepressants don't actually have a known mechanism that directly produces weight gain. Yet, if you look at large-scale analyses, many SSRIs are associated with a tiny bit of weight gain, generally speaking, but then not to the degree of things like, as we know, the really weight gain medications like, let's say, Olanzapine, Zyprexa.
I think that a degree of weight gain that we see on these medications is not fully from the medication effect itself, but is actually from the treatment effect. People, many people, don't eat when they're in emotional distress. That's a normal response. And so if you effectively treat emotional or psychological distress, people may start eating what seems to be a normal amount to them But this is America, right?
And they are eating an unhealthy amount. So some of these medications can apparently cause weight gain simply because of the restoration of unhealthy eating pattern. And so it's not just I've given the medication and a warning. I'm done here. You know, we're physicians, we're people in the health field. We should also have some reasonable counseling and attention to overall eating habits, whatever you can fit in.
Yeah, it's an interesting point that you're saying it's not just a molecule that causes the weight gain. It's the whole treatment parameters that kind of change with the gating weight. Yeah.
In support of that, one of the analyses of SSRIs showed that if you accounted for unhealthy eating, the weight gain signal mostly disappeared for SSRIs. And that's obviously not really true for crazy weight gain medications like Zyprexa. Cerebral.
All right. Now, you know, so weight gain is obviously one of the major things that causes issues with these medications. What are the other issues that you worry about with antipsychotics?
Well, the second, probably most frequent side effect is sedation. Now, sometimes sedation is good, right? A lot of people with psychosis are not sleeping well at night, either just automatically seemingly as part of the illness or naturally because of paranoia, auditory hallucinations interrupting, disrupting the sleep pattern. Okay. So in that case, sedation can be good, but we don't want morning sedation and we don't want sedation during the day.
And a bad habit I see in a lot of inpatients and a lot of inpatient doctors, and this carries through to some outpatient practices, people dosing things twice a day when they don't need to. A lot of these antipsychotics do not need to be dosed twice a day to have effective antipsychotic coverage but they still discharge patients from inpatient hospitals on twice a day instructions to take twice a day they don't convert to nightly dosing when they're readying for discharge on a longer hospitalization and they may maintain people for years on bid dosing let's say a risper at all which really you don't need to do that um when they could be doing nightly only so try to schedule the medication in a way that controls the station to act primarily during the sleep period How do you do that?
Well, ask the patient to pay attention to their sedation and to report it, especially the morning sedation. How long does it last? How groggy do you feel during the day? Try taking the medication earlier in the evening. For example, Zyprexa actually peaks at six to eight hours instead of the usual two to four range compared to other antipsychotics. That's a medication that often some patients should be taking earlier in the evening instead of one or two hours before bedtime.
I'm very happy you brought this up. It also brings us to another thing we're going to talk about, which is causes of non-adherence. One of the big causes of non-adherence is complicated medication regimens, and side effects are obviously a part of that. A big lesson from this podcast, move all your antipsychotic dosing to once a day at nighttime. It makes a huge difference. It improves side effects that you wouldn't even expect it improves.
I think they showed that like akathisia drops significantly, like a percentage that you like is mind boggling in regards to.
Doesn't really make sense either, but it does in many cases.
So, yeah, big lesson here. A lot of times patients get discharged. Risperdal 2 BID. Move that to nighttime. Yeah.
Yeah. I mean, you don't have to do it and you probably shouldn't do it too quickly, right? You want people to be able to adjust, but it's something that you should pay attention to and work with the patient to get to nighttime dosing or at least once daily. Um, even if they prefer it during the day, for some reason, some people are find it better during the day as simple as possible helps.
And minimum side effects is going to help no one is going to even the most dedicated person is not going to be able to withstand taking a medication that just makes
them feel bad all the time yeah um and i think one thing that's really important when you're prescribing medications for schizophrenia is don't sugarcoat things um and also like allow like empathize with patients for how annoying these medications can be. I think it's helpful. I think you have to stay hopeful but also stay realistic. I think by minimizing or not listening to their concerns about sedation or cognitive dulling is really problematic.
As someone who doesn't have schizophrenia, if I don't have my coffee in the morning, I'm basically unfunctional. I can't imagine having to take a medication that dulls my cognitive function every single day. I think it's important to empathize and put yourselves in those shoes. Imagine having every single day to take a medication that really dulls you and makes it so you're not as quick and you're a little sedated and you're not making connections as well as you can.
Non-adherence is a major problem in this diagnosis. And by ignoring these things, we can cause problems.
Yeah. And, you know, you shouldn't ignore this either in the adherent patients. I'm thinking of a few patients where, uh, and it's kind of natural because we expect negative symptoms with psychosis, uh, with psychosis, uh, schizophrenia, um, yet. It looks the same as neurolepsis when you're giving too much dopamine blockade. So I've had a few patients where I thought their baseline was their baseline, but once we tried bringing down the sedation a little bit, they almost changed their personality a bit.
One of them even got worried was getting manic, but no, she was just getting back to normal. after we got her less sedated. Obviously, there's risk of decompensation when you lower doses, and that's something that you want to monitor for, and then you might consider and discuss with the patient, but just make sure you're not neuroleptizing your patients unnecessarily.
Yeah, and to maybe put that in simpler language, because that neuroleptic, you know, it might be a confusing word for some. One thing that's confusing is that schizophrenia causes what we call negative symptoms, which is a motivation, a volition, essentially like, you know, they don't have a will and drive to do things. And on top of that, our medications can cause that. So it's confusing that the thing that's supposed to help can actually cause aspects.
We call it neurolepsis when the medication causes that a motivation or yeah. So it is a little bit confusing.
Yeah. And going back to what you mentioned in terms of counseling patients, it's, we have to emphasize how this is unfortunately, but necessarily a balancing act and a sort of trial and error process. And I tell patients that I'm saying, I want you to tell me how this medication treats you and we're going to work with it to find what works for you. Okay. And that's going to take some time and you're going to have to work with me on that.
But if you stick with me, we can try to find what works best for what you want out of your life. And, you know, in some cases, I will say that I've counseled a trainee on this before. Sometimes some people are OK with having more hallucinations. if they're less sedated. And it doesn't mean that they're going to get hospitalized. You have to assess the patient. But yes, if you want to accept more of this symptom for less of this symptom, that's a fair thing that is in outpatient where they're not conserved.
That is their choice. You have a right to be a psychotic is what I said when I staff that case.
Yeah, and recommending people go back and listen to our Therapeutic Alliance episode if you haven't heard it before. But it's a good point because when we think of schizophrenia, we're thinking of positive symptoms, negative symptoms, cognitive symptoms, and even mood and motor symptoms. But in terms of treatment, we're not just decreasing the positive symptoms, which is what a lot of people conceive of, like, oh, we're supposed to be getting rid of your voices and rid of your delusions.
What we have to keep in mind is that schizophrenia is this collection of symptoms, and they all funnel into the person's social and occupational functioning. And we need to be treating – that's what we should really be focusing on, maximizing the person's functioning. And if we need to sacrifice a little bit of positive symptoms that aren't distressing, that don't cause problems at work so that the patient can maintain some of the cognitive symptoms and some of that lack of sedation, that's okay.
Yeah.
Speaking of how I talk about medication choice at the outset and during treatment selection of patients, I also say we basically have two poles that we can choose in antipsychotics. On one hand, we have the weight gain and sedation effects, diabetes risk. But then on the other side of things, we have, unfortunately, the restlessness and EPS and Tremors, but most importantly, akathisia, and probably, unfortunately, tardive dyskinesia risk.
But I would say that since the risk of weight gain and diabetes and appetite increase and over-sedation is much higher, the chances you're going to get that are much higher than the chances of getting tardive dyskinesia, even though tardive dyskinesia is a very real risk. So that brings us to the other end of things. The medications I do favor that cause less weight gain do tend to be pretty bad for akathisia, and that is Latuda and Abilify.
Latuda is definitely number one and Abilify is up there in terms of akathisia risk. So for that, you got to really remember, you can plan in advance. And I do plan in advance. When patients have told me about history of akathisia, even from the less akathetic medications, or just if the patient is concerned about it, I will give some benztropine, for example, as a PRN. Take this if you become restless.
Don't make them wait weeks or have to take themselves to the emergency room because they're getting terrible akathisia with the medication. There's no need for that.
Now, I do want to poke you a little bit. That's not standard of care. Hold on. What do you mean not standard of care? Maybe I'm using the wrong language. I'm saying that's not. Yeah, I apologize. What I meant is that that's not standard. That's not the standard thing. Yeah.
A lot of people don't do that.
Now, and the reason why, there's a lot of psychiatrists who think that you should almost never prescribe cogettin or benztrapine. And the second thing is that for akathisia, there's a question mark of if benztrapine should be used.
Yeah, and here's the problem. Akathisia is unduly ignored by the field. You're not going to make any money off of researching akathisia, okay? You know, most of the time... People are the same doctors. I'm sorry, we're going to we're going to criticize this imaginary doctor. The same doctors who say never prescribe the Benzterpene are also the same ones who will not blink and give Zyprexa and Seroquel, which are themselves already anticholinergic.
We're avoiding the akathisia in those not because they're not we're not giving anticholinergic burden. but because it's built into the medication already. I'd rather not give the anticholinergic alongside the medication and make it a PRN. Now, so that's the distinction, right? There are also doctors who always prescribe benztropine or Benadryl alongside the antipsychotic as a scheduled medication. You may emphasize, and I even put in all caps of my medication instructions, this is only as needed.
If you get... The symptoms, try it, and if it helps, it helps. If you don't have the symptoms, you don't need it. And I will say clinically, and I would say even in the research, no, the anticholinergics totally work. They definitely work for akathisia, and they'll work fast. It's not your only choice. Long term, I do prefer to put people on propranolol. twice a day. You can get effect from as little as 10 milligrams twice a day for akathisia.
If the akathisia is more like a restless legs thing that's mild and only at night, gabapentin can be quite effective, nighttime gabapentin. Um, and there are some odder ways you can treat it too. For example, a vitamin B can help with akathisia. You can do that. I actually discovered that on accident when a patient of mine, we thought that he was having disorganized behavior, uh, started being given just a random B vitamins by his mother and it completely resolved the apparent disorganized behavior, which ended up being akathisia.
Um, You can give benzos too, or even Lyrica, but I prefer not to go to that unless it's an absolute must. I do have one patient where I was forced to give a scheduled benzodiazepine adenine.
And, you know, going back to the Cogentin, so you mentioned you give a PRN. How many would you give for a month the first time you prescribed it?
I like to start with a half milligram dose, and I say take one or up to two at a time. Call me if you need more than one milligram of the day and I give 30 or 60, whatever I kind of feel like. If I feel like there's someone that tends to overtake medications, I will give 30. If there's someone that is relatively neutral on that front, I'll give 60.
usually I'd probably give a supply of 60 and let them hold on to it because as we escalate the dose of medications like Latuda, the likelihood of developing at least some akathisia is pretty high. Now, you don't necessarily need to give the bensterpine and stick it on forever. okay um a lot of the akathisia is um kind of like what you see with the nausea and diarrhea with ssri it can come back with a dose increase and go away later on it takes a little more time to go away uh i i see an order of several weeks to maybe up to two months but if you treat the akathisia and then have a little trial without the anticholinergic sometimes they won't need additional medication at all in the long term
Yeah, and then I think to provide a counterpoint, I have seen a lot of patients come to me taking a standing Cogentin that... They've been on for a long time. I ask them more questions. Actually, I'll think of one particular case example. I'll change the details. But this patient was on clozapine, cogentin 5 BID, and higher dose imipramine for sexual side effects for clozapine. So I asked – this was in the previous documentation.
Well, it's not weird.
It's just that's a lot of medication. Yeah.
uh imipramine for sexual side effects for clozapine i almost had it i i mean that
makes people try all kinds of weird things i don't do that but it's not really i
that makes no sense to me imipramine causes sexual side effects well you know it's
a dirty drug at a low dose you don't know what's gonna happen blah blah blah um Anything can apparently cause or not cause sexual side effects because the underlying condition can cause sexual side effects too. But yeah, I don't do that. It's just people have tried weird things in the past and believed in it. Obviously, I only go for bupropion and buspurnon for sexual side effects. Anyway, that's an aside.
Let's go back to topic.
So, yeah, I asked the question more details. It seemed like he just had always been on it. He'd been on it for a really long time. No one wanted to make any changes. He was relatively open to making changes. We tapered off the imipramine. We tapered off the cogettin. With clozapine, you wouldn't expect EPS, so it didn't make a lot of sense for me why he would be on cogettin if he didn't overtly have some weird EPS.
He never noticed any difference, and I think I saved him some cognitive problems in the future.
Absolutely. But I mean, that's not a counterpoint. That's a point, right? Um, what I'm saying is that when you see that, um, you don't know what happened, it could have been a reflexive prescription to the Benstrapine, but in many cases, uh, it's because the akathisia is only on the dose escalation or the initial dose and it goes away over time. You don't need the Benstrapine forever. Also, uh, that could have been imipramine associated akathisia, right?
Other medications than antipsychotics can also cause akathisia. Maybe after you took that off, you didn't need the Benstrapine anymore.
Yeah, it's very possible. It's a messy area, though, admittedly. The point there is, you know, cogettin isn't a great med if it's... It's a very bad medication if it's not actually helping with anything. I've heard psychiatrists call it poison.
Oh, I mean, I think that's a little... All anticholinergics are potentially unhealthy. We give tons of anticholinergics without calling them poison. Benztropine is perfectly fine. You just shouldn't give a medication that people don't need. That's the underlying principle. Yes, I agree.
All right. So we've talked about, you know, in terms of the major problems and side effects that with antipsychotics that cause patients to discontinue. We've talked about weight gain, which is a huge one. We talked about sedation. We've talked about EPS slash akathisia. Anything else that pops into your head?
Well, I mean, there's tardive dyskinesia, and we have to consider that. It does seem to be possibly, we don't know, again, more likely to happen in the medications that tend to cause more EPS or akathisia. You can get abrupt withdrawal dyskinesias that can go away or they can persist. A little scary. and it's definitely more likely to happen in people with mood disorders and have schizophrenia so please use your antipsychotics sparingly and only as needed for the clinical picture for as long as they're needed but for the patients who need long-term medium or even high dose antipsychotics, all these, but tardive dyskinesia too, I think we have to emphasize that a lot of these medications are basically life-saving.
Even if they don't literally mitigate life and death, there's a level of a meaningful life that people can live with the medications that they can't live without the medications. Yes, the patient is alive still if he is shut into his room 24 hours a day, unable to concentrate on things because of hallucinations and unable to leave the house because of paranoia, spending all of his time researching his delusions.
That's not good living, though. He can live a much more normal life. um and think straight frankly uh with the medication so i say the patients you know i think this is a medically necessary medication for you something of this class okay and uh i don't just say oh it's gonna stop hallucinations a lot of people they don't perceive the hallucinations as something separate from themselves or as um something that's not real so it's not going to land if you just say this is for your schizophrenia this is for hallucinations no we know medically that these medications are going to help with things like fear stress level sleep and thinking process okay the thinking process will be more organized and less disrupted and therefore you'll be able to concentrate better and live your life better that is true if you have picked the right antipsychotic and that you're dosing it without too many side effects.
So I say, this is medically necessary. I think it's important for your thinking, your sleep, your stress, your mood. I'd like you to find a level that works for you and the medication that works for you.
Oh, yeah, bring up great points. The importance of knowing your patient and what it is that they consider important and the aspects that they feel like treatment is important to be directed towards. So often, especially with early clinicians, they focus on what they think of as problematic. They think of the hearing the voices. They think of the outward signs of talking to themselves. They think of the high cholesterol levels.
These are things that you have to know the patient, these things, they might not care about these things. And if you're explaining to them that they need to go up on their medication because, or decrease medication because, oh, your lipid levels are high, it might not land because they might not understand, like it might not be something that's important to them. So you really have to come to a shared agreement for what it is that you're targeting and the reasons that you're making these changes.
Yeah. You know, that reminds me of a side point I'd like to make as well. In a lot of cases, naturally, because this is such a debilitating illness, schizophrenia, you'll find that there's a lot of family involved if you're lucky, right? If there's a caretaker in the family, especially a parent that helps coordinate care and helps monitor the patient. But you need to make sure to establish from the outset and to maintain that the patient is the primary agent in the treatment, even if they're conserved, okay?
even if they're concerned, because ultimately we do want people to take medications voluntarily and knowingly and by mouth, ideally, in my opinion, uh, And if you focus on things, I've had many parents go like, oh, they're still talking to themselves. The patient is doing it too often. Well, I'm not actually that concerned about that. I want to know, is it distressing to the patient? And do I think that their illness level will actually improve meaningfully versus the side effects by increasing medication?
I'm not going to simply follow what outside observers are looking for, even if they're much more engaged in the treatment process. I want to at least get some buy-in and the personal opinion of the person who's experiencing. the illness and the medications.
great point i do want to reinforce family involvement is huge um the effect size will outperform most medic like it's such a huge part of treatment um it's having family involvement one thing that caught me as a little odd as you said um preferably by mouth for medications why did you say that well because we just don't
have that many choices when it comes to injections and most injections cause a lot of weight gain side effects blah blah blah that's the main reason if we had uh more long acting injectables of different choices so we can pick and choose. Um, and that if more of them were effective for depression alongside the psychosis, the psychosis treatment, I'd be happier injectables, but we just have limited options.
Also, uh, injectables are way more expensive and, um, require a lot more manpower from the healthcare system. So we shouldn't use them unless we really need to.
Now, see, I have a completely different opinion on that. I think that every patient that can be on LAIs and doesn't have a major objection to, I think should be on them. I think they're, well, you know, it's such, especially, I mean, for patients who are, you know, completely bought into treatment and, you know, have good insight. I think PO medication is perfectly acceptable, but LAI medication has been proven to decrease hospitalizations, decrease non-adherence.
I think the choice to take a shot once a month is infinitely easier than choosing to take your medications every day.
I'm going to say it totally depends on the patient. I agree for a subset of patients. There is a subset of patients who can't do that or won't do that. But there's also a large proportion of patients who will. And they can end up on the LAI, too, because of that philosophy. And they don't need to be. And also, the LAIs often cannot achieve the right dose.
Some patients do respond with higher effective serum levels than what is possible in the LAI. And you may be depriving them of that. So, I mean, I agree with you for patients who, again, are unable or unwilling to actually take formal medications as prescribed. But I also have patients who got better because they live with their parents anyway. The parents are perfectly willing to monitor and help with the medications.
And even if the patient's pretty ambivalent about taking oral medications, they don't mind if they're working with mom or dad. And they don't need me on injection anymore. They actually like that better. So it just depends. And yes, sometimes you have to start off an LAI, get somebody more stable, get them more used to the treatment, and then you can have a talk after a year or two and get them to oral.
Yeah, so I think, you know, the takeaway here is, you know, patient populations differ and the patient selection matters. I think I'm just more pro-LAI just because I've seen what a difference it makes. Yeah, it just depends on what you've seen, honestly.
I'm pro-LAI, don't get me wrong. It's just, you know, you don't always need it. And when you've been on it a long time, you can also switch. That's okay. That's kind of what I'm saying also with the Benstrapine too, right? You go by the situation that's in front of me.
Yeah, and I think with LAIs, I like that there's one month, two month, now six month options in Vega half year, which is the cheesiest medication name of all time.
Their names are ludicrous. I love it.
Yeah, and then I guess I'll tell just a little fun anecdote from residency. I'll tell an anecdote from both sides of the story. One of the things I loved about residency is I pulled so many patients off so many unnecessary medications. I lowered doses of antipsychotics to appropriate ranges. I took a ton of patients off unnecessary cogentin, took a lot of patients off, lowered them to appropriate doses or took them off unnecessary medications.
And, um, there I'm thinking, you know, long-term in regards to anticholinergic side effects in regards to unnecessary exposure to antipsychotics. And then, you know, I did have some failures, uh, two patients in particular, they were on LA eyes, um, uh, I guess I'll give a little bit of a formulation. They were bipolar with psychotic features, managed with an LAI. They were on the LAI for a really long time.
I said, you know what? I think lithium can cover you. I think it's worth a trial of trying to get you off the antipsychotic and seeing how you're doing. One patient in particular, I'll make up some of the details so you can't with all that, whatever. Took them off the LAI, had planned to switch them to lithium after they came off. So in the middle of the conversation, they then said they didn't want the lithium and then that they didn't want the LAI either.
They had a very prolonged discussion about the risks. They decided they wanted to come off all medications. And this all started because I wanted to tape them off the LAI. Like the opening conversation was... Yeah. And they decompensated really quickly. And I've seen them decompensate like three more times since then. And I wonder if I had never opened that conversation about coming off the LAI, if they had just continued to take it, would they have had these further conversations?
Yeah, I mean, it's a good object lesson, right? Every intervention has potential risks and benefits. I don't know if you can really second-guess yourself that much other than taking a lesson from it. We can't conduct a number needed to treat a number needed to harm analysis that is meaningful because we're single agents working with specific patients. But yes, be careful in your discussions. Yeah. People are going to make choices.
You don't know if you would have had that choice at some point anyway without making that discussion. You still have to target what seems to be the most appropriate for the long-term treatment plan.
Yeah, and I think it opened my eyes that you kind of pick how conservative of a practitioner you want to be. And if you're conservative, then you're going to have more patients on unnecessary medications, but more stable patients. And if you want to be more liberal and get patients and do more trials of how would you do office medications, you're going to have more decompensations, but more people that aren't exposed to unnecessary medication.
There's no right answer.
It's a pick-your-poison situation.
Yeah. All right. So we've talked about weight gain. We've talked about sedation. We've talked about EPS and akathisia. A little bit about LAIs. I was surprised by your take on that. I thought you'd be very pro-LAI. I am pro-LAI. I'm just not pro-unnecessary LAI. I'm curious, any other considerations in regards to schizophrenia you want to talk about? Yeah.
I don't know how they practice where you are, but where I am, dual antipsychotic is very common. Really? Oh, yeah. And I do dual antipsychotic pretty regularly as well. But that's probably because most of the patients come already on the dual antipsychotic. This is not something I think should happen to everybody. This is not something I think should happen with any regularity. But as a result of this, I have seen that there are patients who respond to dual antipsychotic who do not respond to single agent.
You can never predict it. There's little to no research on this. I think there might have been one large study which actually did show lower hospitalization rates for someone on dual antipsychotic versus single, but Don't do it unless you have to. If you're going to augment your antipsychotic treatment, I would first go back to the diagnosis and try to see if there are any what we might call mixed features or just additional psychopathological features and then psychosis.
Is there any hint of depression, mania, hypomania, mixed depression, sleep depression? agitation, anything that is still not being controlled or that was present in the history, you can find that instead of just ramping up the antipsychotic or even adding on a second antipsychotic or even switching to antipsychotic, that augmentation with, let's say, a mood stabilizer might help. In rarer cases, maybe some kind of antidepressant can help.
In many cases, some sleep stabilization can help. What do I look at for the most? It's probably the bipolar creatures. If there's any hint of bipolar depression or mania, hypomania, I do prefer to use the agents that are effective for bipolar depression, at least demonstrate it to be. But you got to keep in mind just because it's FDA approved, that doesn't mean it's going to work for your patient.
Ultimately, the response to any agent is very individualized. But just don't forget to consider things like lamotrigine, lithium to add on rather than choosing the second antipsychotic. If you have to choose the second antipsychotic, please pick one that actually is appreciably different than the one you're already using.
Yeah, I think I love that you bring this up. I think it's really important because I do see a lot of providers operate as if they're just adding medications to try to fix things. And I think you really need to start with the basics and consider what are the reasons for treatment failure. Yeah. I can think of five important ones. First is you have the wrong diagnosis.
There's so many times that I'm supervising someone and they say, what medication should I add? And I go, what's their diagnosis? And they're like, I'm not really sure. It's like, I need to think through it. I need to have a really strong formulation before I start adding on or switching meds. So wrong diagnosis, number one. Number two is incorrect dose. It could be too high or too low.
Number three is inadequate duration of treatment. Number four is poor adherence. And number five is non-response. So you really need to be thinking about the first four before you're moving to non-response. Yeah, definitely. I'm surprised that you hear dual antipsychotics is highly frowned upon. I almost never do it.
Well, this is the Wild West over here. genuinely i do think there is a tendency for east coast to be more you know not politically conservative though that's probably true too but just more risk averse
and out in the west people try things um yeah i i'm relatively i'm against dual anti-psychotics but i'm curious when when do you consider starting to switch
anti-psychotics starting to switch um I would say this is a hard thing to quantify. To be honest, I would probably describe it as when I don't think I'm seeing as much response to an adequate dose and duration of one antipsychotic as I normally see for the same kind of patient. So based on that patient's level of illness and my skill and experience, I essentially say this person isn't responding to this medication because most people with that condition do respond at this dose.
We should probably try something else because that can just happen. This is an area that we don't understand very well for reasons we don't know why. Simply switching the agent, people can see a response where they didn't on a different agent. I think that's even more true for antipsychotics than it is for, say, antidepressants. And there are a lot of different possible explanations. Yeah, if I don't see you in mostly remission, I'll definitely try to switch as long as you're willing.
And how do you go about making that switch?
That's another thing. Again, I'm shaped by all of my ample experience inheriting high-dose dual antipsychotic patients. So I'm much more comfortable having people on two antipsychotics at once for a fairly prolonged period of time. If you're not in full remission from the disorder and we're not seeing a ton of side effects, I will basically do a very slow taper. I will start the new agent first to test tolerability, sometimes not even changing the dose to the existing agent if it's not at maximum.
And then I will slowly go down by equivalent chlorpromazine doses, chlorpromazine equivalents. So, you know, you can kind of estimate what's an equivalent dose of one antipsychotic or another, even though they're all so different. That's basically all we have to work with. So I'll just step down a little one by one, month by month until we go entirely to the new one.
Awesome. Yeah. You know, some things that I think can be helpful is you look at whatever medication you're using. Chances are you're going to want to use a stronger medication. So let's say, you know, you have Ziprasidone, you're going to want to switch to, let's say, like a Risperdal, like what I would consider, you know, a stronger antipsychotic. um look at try to find the dose equivalent and you can just search dose equivalent for antipsychotics to develop a target dose and then from there there's different approaches so you can taper up the other one and then taper down or you can cross titrate uh one website that's pretty helpful is switch
com do you ever use that one by chance
No, I just go off my knowledge, sorry.
No, for people who don't have the knowledge, it's helpful. It's just a little website where you put in the medication that you're starting with, the one you want to switch to, and then it kind of walks you through what doses to use. I think it's helpful. I should start using it.
I definitely use those calculators for things like benzos that I use a lot less, but I just do it so much with antipsychotics, I know it. What's important is that you do know it, either by using a calculator or otherwise. I would not just ballpark it or do it by feel. We have at least some data on what level of an antipsychotic seems to be equivalent to another.
This gets really complicated when you use a dose-dependent effect medication like Serequil that kind of stops being antipsychotic at some dose. But, you know, that's beyond the scope of like a podcast. That gets really complicated.
Yeah, I feel like there's two things. Seroquel is the one that if you're switching from it, you should probably just leave it and titrate on the other medication and then pull off. And then another factor to consider is partial agonists have the highest binding affinity, so it binds tighter to the medications. So it's harder. If you switch from Abilify to another medication, you have to consider that Abilify is going to hang on longer.
Yeah. And on that note, by the way, very important. If you add low dose Abilify to another antipsychotic, you're actually not adding more antipsychotic. You're taking antipsychotic away because the Abilify will bind more tightly most of the time and at a low dose will not be acting as an antipsychotic. So just be careful, be pretty knowledgeable about the antipsychotics and move accordingly. I'm also going to pick on something you said a little bit earlier here.
I don't believe in stronger antipsychotics. There is only one stronger antipsychotic, and it's clozapine. And so if you can do clozapine, you should try clozapine. But most people can't because of the monitoring, and a lot of people don't like the side effects. But no, I think it's so individual, actually, the response to medications. And if you think one is not as effective as the others, it may be because of either sedation quality of the apparently more effective medication.
You can deal with that by giving sleep support separately. Or you may be using it wrong. For example, Abilify, dosing it below 15 for a serious mental illness, for example. Or Geodon needs a lot of food to be absorbed adequately. All kinds of reasons why you may be not doing enough art of treatment to help an antipsychotic work for a patient.
Yeah. I do want to go maybe say it in easier words, the thing with the Abilify. Abilify is a partial agonist. One thing that can be a little confusing is that... how we're using it, we're using it effectively as an antagonist. So yes, it has more activity than if the receptor was at baseline, but it decreases... Like when we're treating schizophrenia or we're treating the positive symptoms, we're treating the hyperactivity in the mesolimbic area of your brain.
So a bit like these partial agonists act effectively as antagonists. One thing that's a little confusing is... They have a higher binding affinity than the other antipsychotics, which is a separate thing from its partial agonism. So when I say binding affinity, that means it clings to the receptors more so than the other antipsychotics. So your point, as you were saying, if you add low-dose Abilify, it will take the spot of the receptors and kick off the other guys.
Yeah,
and even have some stimulation properties of the dopamine receptor, which is why it's great med to use in a low dose for augmentation of depression treatment. Yeah. Um, you know, we're kind of low on time and if it's okay, I'd like to just kind of rattle off some random pearls that I have about my favorite agents.
Okay. Hey, we gotta, we gotta ramp. We gotta talk up, be hype man for closet being too, but we'll, maybe we'll do that.
Oh, I mean, okay. Clozapine is great. It works great. It's a miracle drug. if you can actually get someone to take it and do the monitoring. But that might be because the kind of people who can take it and do all the monitoring are just fundamentally different people than people who can't, right? Either by virtue of their family structure or their underlying psychology. Now, for my little pearls, these are subject to change.
These are mostly based on clinical experience, and I might change my mind in a few years. So just take over.
Dr. Fu Pearls.
Yeah. Okay.
Abilify. We need this to be a classic section. Sorry. Sorry. What was that? We need this to be a section in every podcast. Oh, yeah. Maybe. Maybe. Give us the pearls.
So Abilify. Keep in mind that with Abilify, they did minimum 15 and all the way up to 30 to get the antipsychotic response in the original trials. And they gave it benzodiazepine as well. So watch for the akathisia and consider that you need to stabilize the sleep alongside the psychotic disorder. Abilify. Also, the main tena and the aristata, it maxes out at an effective serum dose of 20, so don't be afraid to add a little oral on top of it if patients are willing to at least occasionally take oral med on top of their LAI.
Latuda. Food, food, food. And dinnertime, dinnertime, dinnertime, okay? uh it's not going to absorb without that at least 350 calories and it seems to be based on the research and clinical experience uh better tolerate if you take it once at night that's why they're able to raise the maximum up to 160. um food food food but horrible horrible akathisia in many people still possible to power through or treat with additional medication and um It can be really helpful.
Pretty good, actually, for psychotic symptoms as well as mood. Don't be afraid to use Latuda. Raylar.
Oh, wait, wait. I'll just add another pearl. I'll just add another pearl. The ones you need to take with food tend to end with Doan. So Ziprasidone is another one you really need to take with food.
um let's see after that brailar okay brailar is a weird med but a good one uh first of all even though it's available at one and a half milligrams uh go look into the research most responders of mood or psychosis were probably happening at the higher doses but it's variable why is it variable because it has two count them two active metabolites And it takes anywhere from four to eight weeks to get to full steady state on a single dose of all three active molecules from Raylor.
So it can look like it's not working a lot of the time if you simply start it at too low of a dose. And if it's too early on, And especially if you're titrating from another antipsychotic of Raylar and you pull off the old antipsychotic. So be careful of Raylar. Be cognizant of all its weirdness. It's a pretty good med, but you only have a max of six.
And I'm starting to think that for more serious mental illnesses, bipolar and psychotic disorders, that the minimum dose should be three, not one and a half.
I like these pearls. Keep going. Just give us all the pearls. Oh, yeah. Haldol. Haldol.
We're all used to doing Haldol at high doses, I think, from training and from history. But keep in mind that that's from training and history. The chlorpromazine equivalent of Haldol in Risperdal is one to one, okay? We only dose Risperdal up to eight milligrams and we take Haldol up to very high heights because they used to do awful things like dose Haldol until people had Parkinson symptoms and then pull back the dose a bit.
They thought that was good care before. I mean, we just learn more over time. So don't be so gung-ho with Haldol. Keep in mind that Risperdal and Haldol act at about the same level of efficacy. You may not need such a high dose of Haldol is what I'm trying to say there.
More pearls.
More pearls. Well, Risperdal obviously causes prolactin problems. Don't be so gung-ho giving it to your female patients. You can get away with giving a low-dose Abilify to bring that down. But in most cases, I find that it's better just to switch to Asian if you can. But, I mean, it's a very effective medication. And not horrible for weight gain in a lot of people. And also an underrated severe psychotic depression drug.
adjunct and comes in very low doses for your elderly patients, like 25. I already mentioned Zyprexa and the timing, 6 to 8 m. in most cases because of the time to peak. Any other common ones I use? Not really. Not that I can think of.
Yeah, the prolactin with Invega or paliperidone and risperidone, you really want it. They're the ones that are most likely by far to cause a prolactin elevation. You'd expect the first generation antipsychotics to be the most likely. They're probably next after the risperidone and paliperidone. But yeah, definitely.
I think this last section could be like a YouTube short or something.
I don't think we do well with the shorts.
Why is that? Well, I think that's the time I have today. Sorry. Anything else that you wanted to talk about on this topic? It's a broad topic. We've scratched the surface.
No. Yeah. I expected us to spend most of the time talking about therapeutic alliance stuff. I didn't think we would have the whole time talk. So maybe we'll have that.
I suppressed my therapeutic alliance desire today because I thought it was going to be focused on medications.
no i know i know i thought it was gonna i thought we're gonna run out quickly so i think it's such an important topic in schizophrenia that uh yeah and especially
because it's used so much these days right you're marketed people feel comfortable to them primary care doctors give them antipsychotics are um like america's drug we use it in almost everything why it works but be careful they have side effects don't be afraid to give something grisa if you see tardive dyskinesia either
And then the only thing I want to touch on, so Dr. Fu called me this weekend in tears about how few people are leaving reviews for our podcast. Do you remember that?
I was bawling. Yeah, that was a rough time. Please like, subscribe, share, comment, et cetera, et cetera.
No, your generic comments, it's not working. Give me the passion that you gave me calling Friday night at 4 m.
I think it's not working because no one listens to the end of a 50-minute podcast. We should probably say this at the front. Ah, we blow it.
All right, let's end there.