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This is how it works. We're self-starters. Last week, our sponsor was going outside. This week, our sponsor is meditation. Sunlight.
No, sunlight. For the topic today, right? It's sunlight.
Oh, okay. That works too.
We'll probably get to why I said that later on.
Correct. Well, I just wanted to talk about how I've been meditating. That was really the.
Oh, well, tell me more about that, actually. I do want to hear about that.
Started a meditation course after listening to the David Lynch book on catching ideas. Now you'll probably notice I'm pretty enlightened. OK, pretty good.
Would you care to be put on the spot and define mindfulness to me?
No, I told you being put on the spot, I can't do anything.
This is not a mindfulness episode, but we should probably do one at one point.
Yeah, for sure. Agreed. All right. But no, today is on bipolar, and I want to talk about diagnosis and medications of bipolar.
Bipolar. Finally, an area where I can at least claim to be a claimed subject matter expert. I hope this will be a good one.
Bipolar expert Dr. Fu on the line.
On paper, technically.
On paper, it's similar to, I always think of that Office episode where Michael Scott, they say you have to declare bankruptcy. And he's like in the other room and it's like, I declare bankruptcy. That's how expertise applies in psychiatry.
It's true. And if you're early career or a resident and you don't know this, it's actually the case that if you declare your expert matter interests early on and make it known to people, it will effectively turn you into an expert. Because of course you have to do your study and practice accordingly. You know, you can't just say I'm an expert or I'm interested in X, Y, Z and never read or learn about it.
But if you do do that, people will know they'll start asking you things. You'll start looking things up. You'll start seeing those patients. And, uh, before you know it, you will actually be somewhat of an expert yourself.
Yeah, what I'm saying is you actually can declare yourself an expert and not know anything. That's the game.
There's no... Oh, you were being more cynical?
Yes and no. Yeah, I agree with what you're saying. But the truth is, it is like Michael Scott. You can just go, I am an expert in bipolar.
Yeah, that's true.
That's true. I mean, that's me.
But what I'm also saying is declare it early, declare it with good faith, and you will become a subject matter expert. But anyway, OK, that's enough of that. So bipolar disorder. So what do you want to start with?
We're not allowing any pedantic grants today because we got a lot to get through. We got the expert on the line. First things first, I'm curious, how do you make the diagnosis?
Well, it's very difficult. Here's the problem. And I'll try to make this short. The DSM entity of bipolar disorder is artificially separated from unipolar depression. Manic depressive illness, the original entity back in the very early history of psychiatry, Western psychiatry, was basically defined not based on the polarity of the mood. As in, are you sad or are you down? Are you up, elevated? Are you irritable? It was based on episodes.
Do you have episodes and are those episodes recurrent and distinct from other periods of function? So in that sense, what I consider a true or at least something that resembles genetically, biologically a bipolar disorder is not quite what the DSM is. strictly defines, it's more about, do you have a recurrent episodic primary mood disorder? And then you're going to be closer genetically and therefore in medication response to a bipolar type disorder.
Yeah, great point. It gets really confusing because you use the word bipolar, which obviously inherently suggests that there's two different poles that the person's experiencing. But what you're saying is that treatment expectations, it's easier to go off of recurrent mood disorder as the distinguisher from...
Yeah. It's going to help. Yeah. Simply because, um, let's, we will break it down a little bit more in the DSM bipolar disorder, despite the name is defined by the presence of one pole appearing, which is mania or hypomania, right? Now, of course, if you carefully read the DSM, they leave a lot of room. They leave room for things like mixed episodes, right, or psychothymia. But it's saying you must have this pull clearly and in a very easily demonstrated fashion for us to call it bipolar disorder.
And if you practice that way, well, maybe your patient... outcomes may be appropriate for a research study but in my opinion your clinical outcomes are not going to be so great you should be fundamentally asking does this person have a recurrent episodic mood disorder and how does the sleep get disrupted so that brings me to how we should probably be making the diagnosis the aspect of a bipolar disorder that is most memorable to patients when you interview them is their sleep patterns.
Now, some people won't even remember that with some accuracy. It should be noted that many people in manic hypomanic episodes or mixed states will lack memory once they are out of that episode of what was going on at that time. Very common. So you're working with imperfect history by the nature of the illness and you're trying to recall in the past. It's very difficult. So I just start with sleep.
Have you ever had at least three days in a row where you were not your normal self and you didn't sleep, didn't really need it, or you couldn't sleep even if you wanted to, yet you still had energy. And you got to be careful there because if you say energy, some people will automatically assume good energy and they'll say, oh, my energy was awful. Well, no, even the bad energy, you felt awful, you felt tired, yet you kept moving around, couldn't really sit still, you were doing a lot.
That's the increased activity and decreased need for sleep. I would, they're not, necessary or sufficient to make a diagnosis of a manic or hypomanic or mixed episode. But it's just the most frequently recalled aspect. So that's where I go first.
Yeah, that's great. And I commonly call sleep the vital sign of bipolar. And it tells you a lot of information. So which is everyone you kind of you kind of already said this, but would you say that the vast majority of people with bipolar have these sleep changes?
Yeah, I would say that most do. I've certainly run into some rare cases where we have really clear evidence of a manic or haphomanic or mixed episode from hospital records, from jail records, from any kind of records or collateral that's reliable. And no matter what, you don't have independent evidence that they have reduced sleep and they tell you they don't have reduced sleep. I mean, it's a handful of patients, but that's why it's not criterion A.
of the manic or hypomanic episodes in DSM system because it's not necessary or sufficient. And what is actually necessary or sufficient is a marked change in mood, irritable, elevated, overconfident, that's not the wording in the DSM, with increased or preserved activity. I don't think they used the word preserve, but I prefer to use that.
I have a tough question for you. And I do want to tell the listener, I am putting Dr. Fu on the spot. I don't, we don't prep questions beforehand. So, you know, we got to give him some grace. So it's gonna be a challenging, you know, if you had to ask, what would you say are the three most important questions that you ask to during an evaluation for someone has bipolar?
What are the three questions that could be the most information? It seems like you mentioned the sleep question to be one of the main ones. Yeah.
no this is excellent question um it's not so simple as certain questions what you kind of have to do is that you have to ask about certain subjects over time for the patient and so the first thing that you want to draw out is Substance use, substance use, extremely important because of how easily substances, including medication, especially the antidepressants, can cause similar or the same symptoms as mania and hypomania in some people, even if they would never have those episodes without the medication or substance.
So you need to first ask and get a very clear substance use history and medication use history, including and especially The SSRIs, you say, okay, when did you take this? How long were you off of these? Were there any changes on them? Once you have that, then that's the next question is to sleep. So substances and then sleep. You figure out your whole life. Has there ever been a time where you weren't not yourself, et cetera, et cetera.
Sleep disruption, decreased sleep with preserved or increased activity. And then I would say that for the third question, it actually stops being about what we normally think about, which is mania and hypomania. The third question I think is most important to ask about is the history of depression. Now, again, making things difficult, there are a handful of patients with true bipolar disorders who apparently have never had major depression.
OK, it can happen. And, you know, it's been written about in the literature, but most do. So I'm going to be clear here. I'm not talking about feeling depressed or feeling sad some of the time. I'm not talking about dysthymia. I'm talking about major depressive episodes where we clearly have changes. Neurovegetative sleep has changed. Energy has changed. Body feelings have changed. Appetite have changed. Everything's different. lasts at least two weeks.
I say, when was the first time you ever had that? Has that happened to you? And when was the first time? How long did it last? When it stopped, how long did it go away for? Did it come back? If it came back, how often did it come back? Draw a timeline for the patient, with the patient, about major depressive episodes. DSM defined major depressive episodes. And then if you start seeing that those started at an early age, and that they were recurrent, then your suspicion should be elevated that there may be something close to or entirely a bipolar disorder.
Now, can you clarify – you mentioned substances is one of the most important things. Can you clarify if you – why you think that's important? Are you saying that if someone uses substances then and every episode was in the setting of substances that you would think – how would you – I guess substances and bipolar is a complicated issue. Can you go into a little bit more detail?
Yeah, it is complicated. So the detail that I would emphasize here is yes – Apparent manic episodes, apparent hapomanic episodes, and apparent mixed episodes can occur as a result of several substances, including but not limited to stimulants, of course, methamphetamine, amphetamines, Ritalin, less so, but still possible. And also, less known, antidepressants. Simply taking Prozac, lexaprozol off for some people can result in agitation, sleep disruption, or even emergent hypomania.
And while those people can have those substance and medication-induced episodes, you take away those substances and you watch them, they may not have another one without those substances. And so you might say, well, okay, so anytime someone has these symptoms on these substances, that's not a bipolar disorder, not a primary one anyway, that's a substance-induced bipolar disorder. Well, not necessarily, because there are also people... who become more impulsive or their mood changes during episodes and they decide or they feel more, uh, They want to use substances more and they do.
So it's also possible to have the opposite progression where someone is actually getting into a mood episode and that's what causes or contributes to the substance use. And so it gets very murky and you won't know for sure. And so you will need to know patients and observe them over time. But at least on the first meeting, what I want to find out is if they've had these episodes related to a substance and also independent of a substance, including antidepressants.
Yeah, you bring up a great point. I wish I had learned this earlier in training where I – early in training, I felt pressure to make a diagnosis, you know, the first time I met them just because I had been trained or told that it takes – it's impossible to make the right diagnosis. But you can communicate that to the patient. You can say, this is what's on my differential.
This is why I think that. And time is the only thing that's going to tell us what the actual diagnosis is. Yeah. Now, I see so many patients, you know, more complicated cases where you see a patient with a lot of trauma, maybe... This is connected to kind of the substance conversation you're having. A lot of trauma, maybe some mild personality things you're picking up or it's, you know, not overt.
And their reports of mania aren't really that clear or, you know, everything feels so muddled. With those patients, how... How do you make the diagnosis versus when it's, you know, there's all these, there's always an explanation for why they were experiencing the hypomania. Yeah. Do you have any thoughts on that?
Yeah. I'm going to go to, you know, in terms of how you make the diagnosis, I'm going to go to another meme. That's the neat part you don't, right? For those patients, I often settle on to and even remain on long-term, an unspecified mood affective disorder diagnosis or other specified bipolar or other specified depressive. disorder diagnosis. And why? Well, we have to really draw back, I think, and think about what we know and what we don't know.
We don't know what's really driving the problems for these patients. Some people have very strong opinions. Some people, very personality focused, will say, oh, it's entirely personality. Some people, very biologically manic depressive focused, will say, oh, it's a manic depressive illness that's mild, that's being exacerbated by things like trauma and stressors. And the trauma-focused people will say, well, that's entirely a trauma disorder. I'm going to say I'm agnostic on it.
I can't say what's causing that when I don't have enough medical evidence to say one thing or another. So what am I going to do? Well, I'm just going to watch and I'm going to use the minimum amount of safest medications I can. And I'm going to try to address every issue that I do find with that patient that could get better. And fortunately, regulating the sleep tends to help everyone, regardless of the diagnosis.
So that's not too bad. And we just don't know enough to say more. You know, we have to consider that there are identifiable genes that are seem to result in some people needing less sleep. It's also possible that that gene, combined with certain traumas, certain stresses, in a temporary way, will induce a brief hypomanic episode.
We don't know.
We just don't know enough.
I think the bipolar spectrum disorder is a pretty helpful concept here. Nasir Gaby is kind of the big guy behind it. It's for those patients in that he defines it as at least one major depressive episode, no spontaneous hypomanic or manic episodes, and then either one of the following, a family history of bipolar and a first-degree relative or antidepressant-induced mania or hypomania, and then a few other criteria if those aren't met.
really helpful concepts for that helped me to understand why a patient who maybe doesn't have that overt history of hypomania or mania could benefit from mood stabilizers.
You know, it makes me think, by the way, as you mentioned that, that it's I've read that Europe is much more willing to give lithium as adjunct for the treatment of what seems to be a unipolar depression than we are, you know, and I think they may be onto something there. And I think that our practice here in the S. of giving a lot of second-generation antipsychotics for the treatment of supposedly unipolar depression as augmentation, we may be treating something more in this spectrum of manic depressive illness.
Yeah, I think it's going to be a good transition to talking about medications. First, I want to hear about your approach to medications. I can ask specific questions. Do you want me to ask specific questions?
I can just jump right in. It's funny because I was just talking about this with a trainee yesterday, so it's fresh in my mind. This is something that is probably, I would say, in the core competency of any outpatient mental health clinician. The first thing I want to say is that this is controversial to some extent. There's still debate about whether or not you can and should give antidepressants specifically and particularly SSRIs, SNRIs, and bupropion.
Can or should you give these to people with antidepressants? bipolar disorder. Okay. Lots of psychiatrists say, sure. As long as you have mood stabilization, it's fine. I am of the camp to say, I'm going to avoid them like the plague unless I can't get away without using them. So the first thing I'm going to say is that if someone is on a antidepressant and they're rock solid stable, then fine.
Okay. Uh, keep it on, but watch it, but don't be afraid to pull that thing off. Um, and don't start it unless you have no other option in bipolar disorder, uh, It's destabilizing, in my opinion. It's more likely to make people cycle. That's the number one thing. Number two is, of course, mood stabilization is king. Yes, it's much easier for patients to avoid the labs, for you to avoid the headache of the labs, and the side effects sound scarier on mood stabilizers and antipsychotics, but please do the mood stabilization first.
Use the mood stabilizers. Use the proven ones, and don't be afraid to use even two mood stabilizers.
Completely agree. You mentioned it's controversial, but I hear we're in the same camp. You know, and I think an important thing for approaching bipolar illness that's been helpful is, you know, with depression, there's really just two states, two major states, you know, either the person's doing well or they're depressed. Bipolar is not like that. And you really need to break it up into three separate things that you're treating.
You're treating bipolar maintenance. So how do you prevent mood episodes? And I think that's understated in a lot of people's approaches these days. You're treating acute mania and you're treating acute depression. And... I think that the focus really needs to be on the maintenance, whereas with people using antidepressants or second-gen antipsychotics, today you see more of the focus on kind of just throwing meds without really a consideration for those three different treatment approaches.
Yeah, absolutely. And a great point. And I don't blame anyone. It's easy to focus on the here and now because the here and now is what we're feeling and thinking about. And it's not fun to be in an acute mood state. It's disabling and it's unpleasant, right? But when you pick treatment and you plan treatment, you should think not just one month ahead, but five months ahead and five years ahead.
You should think in the long term. And so to that end, when I start treatment for anyone who's in mixed manic or hypomanic, I also need to give them an expectation of what's to come. So I say, look, for your condition, the best thing for you is we get you on a mood stabilizer. But this is what might happen as we get you on the mood stabilizer in the next few months.
First of all, I expect you're going to start sleeping better, but you have not been sleeping right for insert amount of time. Sometimes it's weeks, sometimes it's months, sometimes it's years. Okay. So you're going to start feeling tired. Okay. You need to catch up on your sleep. You have sleep debt. It is totally not possible for us to fix that sleep pattern of yours and for you to not feel tired until we get you settled in.
Second of all, you're going to start maybe even feeling depressed. And that's because The way these medications work, we're only preventing the aspect, which is your brain going too fast and not sleeping. And the brain going too slow, we're going to have to address that when it comes in a different way. So keep in contact with me. Expect it. Maybe it won't happen to you. And that's great.
But if it happens, we're going to work on it. And if you don't tell people that, then it's very normal for them to say, wow, I'm taking this mood stabilizer. I feel tired and depressed. I should stop it.
Yeah, that's a great point. I haven't actually explicitly said that for most of my starting lithiums. That's a helpful point that expectations are so important and focusing on... We're going to do an episode on the therapeutic relationship, but focusing on the long term here is really how you win the game. Setting expectations, letting patients know. I think to put another way of kind of what you're saying is...
Don't focus on the symptoms. Don't treat symptoms. Treat the disorder. And when you're doing treatment for maintenance, you're treating the disorder. And I think that's kind of the point you're emphasizing. So when it comes to maintenance, you mentioned starting a mood stabilizer. What medications are you reaching for?
Well, the popular ones are, of course, going to be the evidence-based ones. And what we have is Lamotrigine. which is the weakest, but also probably the best tolerated. We have lithium, which is the gold standard, the classic. And we have Depakote. Works great. There are some problems with it, especially with both male and female fertility. So I don't tend to use that one as much. And then finally, we have carbamazepine and oxcarbazepine.
Those are not liked by people. I don't like carbamazepine because of all the medication interactions it has, but I'm happy to use oxcarbazepine. So unfortunately, we don't have a ton of choices when it comes to mood stabilizers that have been proven for bipolar disorder. We can speculate about the possibility of other anti-epileptic drugs working because, for example, carbamazepine, oxcarbazepine, Depakote, these are all anti-epileptic drugs too, and they work, maintenance and acute phase of bipolar disorder.
But that's basically what we have. Gabapentin, the evidence is not there as a primary mood stabilization agent. Don't think about it that way. But I encourage you to think about it as an adjunctive treatment in bipolar disorders.
Yeah, and then I will say in terms of something you said there that is potentially controversial, oxcarbazepine typically isn't on people's top list for maintenance. It's typically considered not as effective. That's true.
Yeah, that's true. But there's at least some evidence for it. And yes, it's old mixed evidence and people say, oh, I don't like it. But the action is, you know, at least meaningfully close to the carbamazepine. I think it's fine to have trileptal on your top four.
Yeah, for me personally, I typically have lamictal, valproic acid and lithium. And then I have the other ones a little bit lower on my list. Same here. That's correct. Now, I kind of really want to jump into lithium. You mentioned lithium is the gold standard. One of the most probably underutilized medications, one of the best medications we have in psychiatry. I kind of want to get into the nitty gritty to help people prescribe it more often.
Probably the biggest hindrance to people prescribing it is monitoring. Can you talk a little bit about the monitoring? And then I'll guide you to some questions.
Well, you know, you're supposed to monitor. Why? Look, lithium is great. Helps up mood, seems to be neuroprotective, prevents dementia, maybe in people with bipolar disorders, uh, works great. Um, not too bad in terms of the side effect profile, but, um, dosed adequately it's a salt and it's processed by the kidneys. And therefore you probably are buying good brain in the longterm for some kidney function decrease in the longterm.
And so there's that and there's problems with thyroid potential effects as well. So that's why we monitor. The British are a little bit more, you know, responsible. They try to get, I believe, two sets of labs within the first three months. I try to get two sets of labs within the first six. And I try to get once a year after that. Some people do once every six months.
I think that's a little overkill. I just want to monitor for that. In terms of other things that you watch out for, well, you have to understand that lithium being a salt is going to produce some level of thirst and drinking and therefore urine production. So it's actually very common for people to notice increased urine production with lithium. And if you're not experienced with lithium, this can be a little bit concerning.
because you're going to also read about what used to be called diabetes insipidus that may occur from using lithium. Just keep in mind that that's a much higher volume of urine production than the normal polyuria of lithium administration. So you look out for thyroid, you look out for kidney, and you look at the level. Now, the level, historically, we try to target around 75. Personally, I would say that the level of lithium that we have in the literature is geared more towards control of severe bipolar disorders, bipolar 1 disorder, hospitalized bipolar disorders.
You can get away with lower levels. in outpatient. But monitor carefully and don't be afraid to increase the dose. Final pearl, the level of lithium being regulated by the kidneys means that it will be impacted by other medications and other behaviors. So since it's a salt, you eat too much salt, you're going to kick the lithium out. You eat too little salt, you're going to hold more lithium in.
You take any NSAID, it's going to hold the lithium in. It can even make it go toxic if you take a lot of it. and there are certain blood pressure medications that will also interfere. So these are all things that you have to discuss with the patient beforehand. They have to monitor and think of how much more hassle that is than just adding on some mobilifying. That's why people don't use it as much in the United States, but I really encourage you to do so.
That's interesting what you said about monitoring. So you said you try to get to, I guess, yeah, what's the most basic, walk me through your average patient for what labs you're collecting and when.
Yeah. Why too early on? Because we're just trying to rule out that someone has a rare reaction to the lithium for organ problems, for example. And we want to check the level because everyone processes it differently. Now, by the way, the studies of the lithium levels are usually based on the immediate release, dosed two times or three times a day. You always draw 12 hours after the dose, but before the next one.
But in outpatient, I only give most of the time once daily lithium in the evenings. There's a lot of writing on this online that tells you about all the details. I think it's easier to do and better tolerated. But that means that your lab result is going to look higher than what it should if you do once daily at night extended release. There's a lot of nuance about that.
I'm not going to get into it. But in the first, what I do is this. I start the lithium. We get it to kind of a reasonable dose that can be tolerated in outpatient, usually 450 to 600, as much as 900 to start. And then once that's on a steady dose, within the first month, I want them to get labs. And I want to check the lithium level.
I want to check the thyroid panel. I want to check the combined blood count. And I want to check the comprehensive metabolic panel. That's going to show you pretty much everything you need. Then if they're still on that lithium dose, or even if they've gone up within the six month mark, I'm going to get a second set of labs, usually at least one or two months apart from the first lab, just to see if there's any changes, no changes.
Everything looks good. We're going to stick with the same labs once a year.
And what about thyroid labs?
I mentioned that thyroid panel. That's every time I get it.
Every time you get the full panel.
Yeah, well, I get the full panel to start with. And for long term monitoring, I may just do the TSH with reflex, meaning that if the TSH is abnormal, they'll get the other levels.
And that was incredibly helpful. What formulation do you typically use of lithium?
only use lithobid or ER, the extended release format. Again, complex reasons why, but basically because it seems to be better tolerated and is probably better for your kidneys in the long term. Once nightly, easier to remember as well.
I was under the impression that the non-extended release is better for the kidneys dosed once daily at night.
Um, I think it's debated. So don't take what we're saying right now, uh, for that, I do the extended release. I think maybe there was some data showing immediate release is better. I remember weighing the data and looking at the long-term side effects, efficacy and tolerability. I do immediate, sorry, extended release once nightly.
Yeah, and I think that this conversation is actually helpful because I think how we went through it is actually the correct, like this back and forth. There's no, it's not entirely clear. I was like the, you know, what I learned was that without the extended release, your kidneys get a little bit of a break. You know, the extended release helps it so that the peak levels aren't so high.
Yeah. So it's like, do you give it the break or do you want to keep the peak level lower? There's just not a lot of data about it, but there's some data and you kind of have to just make your determination as a clinician.
Now, what about switching medications to lithium? Anything that you need to question? Yeah. I'm sorry. I know it's a huge question. It sounds like.
No, no, it's not a huge question. It's a very important question. You're remembering all the right stuff to go to and talk about it because you know the answers really. Uh, so yeah, when you switch to lithium, you got to remember that if someone is in an acute state, uh, It takes up to two weeks to really start kicking in, and it's really not going to kick in unless you get to an adequate dose.
And that's different than adding lithium to someone who is currently stable. So plan ahead. You may not be able to get to a good treatment effect. I usually don't take away the existing mood stabilization or treatment while I'm adding the lithium on. I want to make sure the lithium is well tolerated. and gets to the right level. Now, if someone starts getting side effects, too sedated, something like that, then I'll start peeling off to other medications.
But just expect that for lithium, it may take some time to get to onset and to steady stabilization.
Now, general, you know, big picture rule of thumbs for when you're picking Lamictal, when you're picking Depakote. Yeah. What would lead you in a direction of lithium versus Lamictal or a different food stabilizer?
Well, I don't use lamictal for acute states, and you shouldn't either. Most of the evidence shows that it's for prevention. Less effective for acute states doesn't mean you can never use it in an acute state. No, but I wouldn't use it as the only medication during an acute state. If I'm adding lamotrigine on during an acute phase, it's because I'm expecting it to function as a maintenance treatment while I'm treating the acute phase with another medication like a second-generation antipsychotic.
Lamotrigine, good for people who don't want to do the blood draws so much, want to get pregnant, for example, because you can take Lamotrigine during pregnancy, seems to be safe and fine. And also for prevention of depressive episodes, people that have more tendency for depressive episodes, Lamotrigine may be a little bit more helpful for that. Lithium is kind of anyone can benefit from lithium if they can tolerate it.
So it's the go-to beyond lamotrigine. Now, Depakote is historically, and in my opinion, better for irritability, aggression, and people with things like a little bit of TBI history and people that have migraine headaches because Depakote works as a preventative agent for migraine headaches. But I shy away from Depakote for anyone who can take the other mood stabilizers unless they love Depakote and they have no concerns about fertility.
And then we get to oxcarbazepine and carbamazepine. Those are indeed the agents I go to when I can't use the last three I just mentioned.
I think there was a funny thing in the UK. They issued like men need to use condoms if they use Depakote. I wonder how that all affects. Yeah. Yeah.
Because there's now some emerging evidence that impacts even male fertility. So, yes, I'm with the British with this. I'm not very keen on the Depakote personally.
Now, what about second gen antipsychotics for mood stabilization? Yeah.
Sometimes you just have to go to that. And I think this is a reflection in part of the... little how little we know about psychiatric conditions some people with bipolar disorders just seem to need a antipsychotic in order to give them the right mix of effects to do well and some that's just something that you have to go with now what are the second generation antipsychotics good for not all of them because these are all very different medications within the same class but generally speaking for bipolar disorders they work for maintenance for acute phase and they also work some of them, for bipolar depression.
That's why they're so popular. You know, why fuss with the labs and the mood stabilizers? We can just get one medication that treats everything. Well, why not? Because of tardive dyskinesia, right? Tardive dyskinesia, permanent involuntary movements of the face, mouth, or body that come from antipsychotic use. And it's higher risk in people with mood disorders. Interestingly, if you have a schizophrenia, whatever is going on with that seems to not be as vulnerable to tardive dyskinesia.
Keep in mind also that there's risk of emergent dyskinesia when you rapidly withdraw an antipsychotic. That can happen. Thankfully, often in those cases, it's not a permanent tardive dyskinesia, but who knows? It's a scary thing for me anyway as a clinician, so I warn people. please take this medication only as directed and let me know if you want to get off of it. We'll taper it off.
What are the best choices out of these? I would say it's the things that have evidence also for bipolar depression. Why? Because if I'm going to give you an antipsychotic, I want it to work for every phase of the bipolar disorder. So naturally, that's Latuda. Unfortunately, Latuda has The most akathisia risk, that's the restlessness of every antipsychotic, probably. Vralar is good, but Vralar takes six to eight weeks to get to level at a given dose, so it's slow acting, even slower than lithium.
And The other ones I don't use as much because of cost reasons, so I don't know them off the top of my head, but you can get away with, even without the FDA approval. I find some efficacy with low-dose Zypraxa, low-dose Risperdal. And remind me, Dr. Malzberg, is it Fanapt or is it the...
capylaida i think it's capylaida that has it's confusing it's it's not fan apt yeah and i i fan apt is illoperidone which doesn't uh yeah your uh vraylar cariprazine has some data and capylaida lumeteperone has good data okay so capylaida
lumeteperone uh vraylar which is cariprazine latuda which is trazodone, are probably going to be the top three picks for a second-generation antipsychotic for bipolar disorder. Beyond that, I am willing to consider Abilify, but keep in mind that they have tried it for acute bipolar depression, not great efficacy. Odd, because you can use it as an augmenting agent at low doses for unipolar depression. I am perfectly willing to use Risperdal and Zyprexa, but unfortunately, Those medications cause a lot of weight gain, appetite increase.
And then Seroquel is approved and effective. But again, with the side effect profile, I personally don't use it. But if someone doesn't gain weight from it and they're not overstated from Seroquel, it's a good choice then.
Now, the lithium monitoring seems so complicated. I think I'm just going to use antipsychotics for maintenance for bipolar from now on.
You know, and a lot of patients do choose that, even though I give my warnings and my recommendations. And that's fair, right? You get to choose how you want to live your life. And it is more convenient. And a lot of the times people do feel better and do better on just the antipsychotic. It's just one medication. But I say to people with bipolar disorder and to the clinicians, please give the mood stabilizers a fighting chance.
You may find that things go better for you body health wise, mind health wise in the long term.
And for the listener, I was making a joke. I don't, you know, I think mood stabilizers are underutilized. Now, Dr. Gamey has this whole thing that he says second gen antipsychotics are not mood stabilizers. Can you explain that a little bit? What does he mean by that?
I think he's referring to a class issue and an action issue. They just work differently. My understanding is that he does not consider them disease modifying. He does not consider them really helping to underlying conditions so much as masking or maintaining the issues underlying it. I will admit I'm not familiar enough with his core argument. You could probably enlighten this better.
Yeah. What you said is pretty much nails it. And then I'm probably butchering it. But there's some, you know, the studies are done by in ways that make it so that the antipsychotics are guaranteed to work or something odd that I don't quite understand.
Oh, right. Yeah. The evidence looks so much better for the second generation antipsychotics because you can argue they're being goosed. And I do think they're being goosed. It's because they're new. They make money for the companies. That's not necessarily a bad thing because we get innovation, but it weighs the evidence oddly so that older medications don't get recommended or considered because there's no money in pushing them forward.
And how can you goose this, you might ask? Well, in the FDA approval study, you more or less have to get clinically significant, statistically significant change in eight weeks. OK, that's pretty fast. So let's take the Abilify approvals. How did they manage to get that effect with Abilify in eight weeks? Well, first of all, they started at 15 milligrams, and then they easily went up to 30 milligrams pretty quickly.
And on top of that, they used benzodiazepine. I believe it was lorazepam as a PRN, and it was basically on board. So it was really dual treatment that they got the approval on. Doesn't mean it doesn't work, but keep in mind, if you're seeing people in acute phase and they just give them five or 10 of Abilify, you are not giving them the FDA approved treatment.
Yeah. My understanding is that they use enriched design studies, um, for clinical trials for antipsychotics, uh, which makes it more likely to show or artificially efficient, like, uh, inflates the response to these medications.
Can, can you say more about whether enriched design studies?
Not really. My understanding, I'm not a researcher, but my understanding is that the patient has to have already responded to the medication in the acute trial before they continue it. So it makes it look like they already know that the patient is going to have responded to the medication. That's what that means.
Okay. Yeah. I mean, there's other issues known about clinical trials. Well... In their credit, the placebo effect is not a placebo. The placebo is a holding environment, people checking in on you, almost a psychotherapy. So when you see low effect sizes in these studies, it's probably because the placebo is so good. Okay, it's not just a placebo. But then on the other hand, yes, most clinical trials can only be run.
They cost millions of dollars. You can only run them by getting professional patients. OK, you can't really spend all this money and have patients who you don't know whether or not they have the disorder or they might just drop out of your study randomly. You know, that's going to cost you a lot of money. So you more or less have to go with easier and confirmed and patients that just go from study to study.
There are patients who do this. You know, they pay. They give you a place to live. And so it's is it the same clinical population as what we work with out in the community? Probably not.
In the interest of time, I do want to move towards treatment for acute mania. What's your general treatment approach there?
Acute mania? Well, I usually do a combination treatment. I think of three main things. So the mood stabilizer, I want to solve that and I want to start it. Whatever one we can get on. But I also know that that one's going to take some time to work. So on top of the mood stabilizer, I want to give second generation antipsychotic. If you are in an acute phase, I give a second generation antipsychotic.
I discuss and, you know, my plan is that's going to be temporary. But I do give that and we discussed which ones we're going to use. And I really want to pay careful attention to sleep. It's possible based on the ones that you choose between the mood stabilizer and the second generation antipsychotic that that's not going to adequately address the sleep. So especially in more severe acute phase, I am not afraid to even add the benzodiazepine.
I'm not afraid to add extra sleep medication. You guys can check out our podcast episode on sleep in order to see the choices there so yeah let's say we're
talking about a more severe acute mania where you know a bubbling mania that has higher risk what antipsychotic are you reaching for and then what um benzodiazepine are you reaching for and are you starting well at the same time what's your general
Yeah, I'm starting them all at the same time. I'm not kidding. And what I reach for, I don't reach for. I offer all these options. And I tell people, what stands out to you? What are you willing to go for? You know, I try to go with whatever the patient feels more comfortable with. I don't see a lot of point in pushing something.
Dr. Fu, whatever. Dr. Fu, I trust you as my doctor. I trust you. Anything you say, I don't even want to hear.
So you're saying, what is the Dr. Fu cocktail? It's lithium. Okay. And... It's latuda, and then it's gabapentin. And why? Because I find latuda to be effective quickly and at low doses. Lithium is most effective long-term. And then why the gabapentin? Because the latuda tends to cause akathisia, and the gabapentin can help with that in the short term. I may also give benstrapine as needed if the akathisia is particularly bad.
But if the patient can take food every night with dinner, take a latuda, take a lithium and is responsible with taking PRNs as needed medications, taking gabapentin, then that's probably my first trifecta.
You do Lututa for acute mania as your first line?
Absolutely. Let me... Tell you another thing about that. Yes, they warn you about it. OK, and I was wary of that early on. But I also noticed that I don't think they even tried to get a indication on Latuda for mania or hypomania. I don't think they tried. And it does not make any sense that based on the drug action that Latuda would work on acute schizophrenia, but not acute mania.
Okay. I think they wanted to sell Latuda as the bipolar depression med. And so they only studied it on bipolar depression. I could not find even a failed trial on bipolar mania. And in my clinical experience, it works. Oh, and of course, if the gabapentin is not sufficient and they're still not sleeping temporarily, I tend to give either Klonopin or Valium for the benzodiazepine. Valium is probably a little better, easier to taper off of.
Klonopin can be a little hard to taper off of. I wish it came in smaller sizes.
So you start all these medications, the patient, mainly it breaks, they're euthymic. How long are you continuing the Latuda?
That one, I try to get off more. Well, first, I try to take them off any benzodiazepine if they're already off of that. But yes, next I say, let's try to get you off of this antipsychotic. I want to see them in euthymia for probably two or three months at minimum. And I just go off of patient comfort at that point. But sooner is usually better. And unfortunately, you can find that if you take it off, people will have relapse of depression.
or mania. It's a delicate balance. It's a delicate area. And unfortunately, polypharmacy is usually more the rule than the exception for the treatment, the proper treatment of manic depressive illness. You know, I'm going to prevent you from asking me the follow-up question because I do want to emphasize something. When we're talking about tiered treatment of bipolar disorders, as I mentioned, my first thing that I think of is no antidepressants.
The second thing I think of is mood stabilizers. But the third thing I think of is not antidepressants. antipsychotics the third thing I think of is can you guess another mood stabilizer no but that yes that's good oh no the third category major category in the treatment of any bipolar disorder is lifestyle changes okay i want people regulating tricky their sleep and life cycle okay this is even its own psychotherapy for bipolar disorder i believe it's uh social and interpersonal rhythm therapy uh i want people sleeping at a steady pace i want them active in the morning and getting sunlight and active during the day i really needing them off of any substances that could be destabilizing that and i want them engaging in some kind of life activity that keeps them active during the day and sleeping at night that's a huge part of the long-term treatment and can lower the need for medications most of the time people do need medications lifetime unfortunately but you can lower the amount that you need to use um
Yeah, I think it's interpersonal and social rhythm therapy, which I feel like the name itself, it's a cool name. Yeah, it's pretty good. Human beings love stability, keeping routine, normalizing your circadian rhythm. Yeah, it's huge for bipolar. Now, the other question I wanted to ask, which is similar to the previous one I'd asked. So how long... Now, I guess I'll just move to bipolar depression. How do you approach that?
Let's say you have a patient, they're on lithium and they start to experience a little bit more depression. What are you reaching for?
I'm reaching for psychotherapy personally, and I'm reaching for lifestyle changes. I'm going to be interviewing them about what they're doing in their lives and what they can do in terms of behavioral activation, more interpersonal contact, doing something different in their lives to help them treat that depression without medication. But... Sometimes I see someone, they're chunked into a major depressive episode. This absolutely happens. It's not any kind of stressor that I can identify or that they can identify.
It doesn't seem to be some kind of lifestyle change that they need to make. Then really, unfortunately, the best thing that you can do is go temporarily again to those second generation antipsychotics that have some kind of proven efficacy for bipolar depression. I like those the most for the use. I find that they get the best response most quickly. And again, I try to make them temporary.
And then if those aren't really working, unfortunately, then we start to get into the antidepressant realm. And again, I try to avoid that. What are the antidepressants that I find a little safer? Not Wellbutrin, not Bupropion. That's what kind of is out there in the community. Kind of myth, if you ask me. I don't think we have any data to demonstrate that. And then I think Trazodone, higher dose Trazodone, if tolerated, is fine.
TCAs can be okay. It's kind of mixed. I would be careful. Very, very careful. Don't go straight to that. That's a last resort. Mirtazapine, not a bad choice. Buspar, not a depression treatment that can be helpful as adjunct. Not a bad choice. Seems to be less agitating.
Yeah, and I think you had mentioned your list of antipsychotics that you typically reach for, and you put serifical a little bit lower on the list. I will say that a lot of guidelines, I think, rank serifical higher than your opinion. And I'm not saying that's good or bad.
And again, it's not about efficacy. It's very efficacious for me. I know it works. It does work well. It's about the side effect profile. That's why I don't rank it high. That's the only reason. Yeah, I mean, Seroquel, if you look at the studies as effective as lithium and maintenance in some studies. Oh, wanted to mention also for the depression component beyond that, TMS, I am seeing some pretty good effect while your mood stabilized seems to be helpful.
And you can consider esketamine for some patients, but you should really be familiar with how that medication works and why. before recommending that, in my opinion. And then finally, of course, there's electroconvulsive therapy, which nobody likes and everyone's afraid of, but it is an option.
yeah and hopefully uh we're gonna get dr owen muir to come on to the show we're currently in uh discussion for scheduling a thing so i'm really excited about that um that'll be good he's gonna be our our resident tms expert um now how long okay so you start the second gen antipsychotic person goes you meet a few months later doc i'm not depressed how long are you continuing that second gen antipsychotic for
in Again, up to them. I will say, hey, you know, you've been well for a bit here. I think it's worth trying off of it and see how you do. And that does depend on my non-scientific appraisal of their life status. How's their life going? How much stress are they having? How well have they carried through with things like behavioral activation and sleep regulation? I offer it.
Like I said, I'm Well, let me think about what I really do. I think if someone's generally in remission from depression, my practice is actually to go minimum six months of remission before I move the medications. But in bipolar disorder, I'm willing to go probably a little bit earlier. It's just because of the side effect profile of antipsychotics. So there's no science here. You just kind of have to go off of values and judgment.
And what would be like the earliest you would consider?
Well, it's not up to me. It's up to the patient. But the earliest I usually consider is about two or three months of remission. That's very early. I really don't usually do that. Probably six months.
Now, we've talked about a lot. Is there any major aspect or question you think that I think we should go into?
No, I think it's like an avalanche of information, especially if you haven't encountered it before. If you've encountered it before, I think it's a good review. But this is such an important topic. I think the diagnosis of bipolar disorder is super murky out in the community. I do think it's underdiagnosed. Many people think it's overdiagnosed. As a personality disorder enthusiast, I feel like I'm pretty decent at picking them apart.
but it just depends on the practitioner. But I have my usual message, you know, call it whatever you want, but just give the right treatment. And if your mood stabilizer is helping, maybe they do need a mood stabilizer. The other thing is, yeah, I really want to emphasize, and if you make some of those nice charts again, Dr. Malzberg, if you can do the one, two, three, one being...
be wary of antidepressants to being mood stabilization and three being lifestyle changes and sobriety. Those are the three hallmarks to me of bipolar disorder treatment.
Love that. And as you mentioned, this is an avalanche. I will say I am currently working on a bipolar course. Hopefully we'll be out in March, which will be the stuff we just said, but much slower. Um, there was actually, uh, yeah. And I love those three things that you bring up. Um, There was something I wanted to bring up. I put out a video on the mood spectrum, and there was a comment that I really liked.
No, I think this was a good one. I hope it was a good one. Yeah. Thanks for listening. Like and subscribe and all that. Tell your friends. Let us know how we did.
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Oh, that was a little non-optimistic. We are growing, but we'd like to grow faster and we appreciate your help.
I think it was more pathetic than non-optimistic. Just begging. Well, I didn't want to say pathetic.
All right. Well, I'll see you next time. Have a good one. Have a good one.
Thanks for listening.