Welcome to the Psychofarm podcast. This podcast is for education and entertainment. It certainly is not medical or psychiatric advice, diagnosis, or treatment. Listening does not create a doctor-patient relationship with me or Dr. Fu. If you're a patient, certainly don't change your treatment plan because of something you hear on the show. If you're a clinician, do not use this podcast as a clinical reference or substitute for your own training, judgment, thinking, and up-to-date sources.
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Good morning, Dr. Malesberg.
Good morning. How are we doing?
Well, it's been a little while, though I don't know if that reflects itself in the release schedule.
Yeah, I got some posts to read to you. There was a Reddit thread. So someone brought up our podcast and they said, I cannot stand the podcast. The banter between the two is like nails on a chalkboard to me. And then I thought it would just be a solo personality disordered person, of course. Turns out that it seems to be a relatively popular view. Agreed. He used to be good, but not anymore.
Yeah. And then listening to the first five minutes of an episode, I realized it was making me mad. Life's too short to listen to those two guys talk stupid to each other.
Wasn't that the first person? That wasn't the same guy as the first person? It was the
same guy. That was the same guy.
That's like two people. I thought we were going to not mention that. I thought it was a little petty. You're going to have people who don't like you, but I'm going to take the full blame for this. If people used to like you and don't like you anymore, that's obviously me. That's that, man. That's that.
Well, the thing, how I think about it is when I was making the videos, my personality didn't come across. Now that my personality comes across, people find us like nails on a chalkboard.
It's like two people. I do think that personality doesn't exist alone, right? Personality exists in combination with other people, at minimum a dyad, and even when alone, if we think about psychotic disorders, We almost invent other people. We have internalized them. We interact with them. So there's no such thing as a solo personality. Your personality pre-podcast, I think, would have been the you interfacing with sort of this invisible audience of learners, right?
And now there's a dialogue. So it's still me. It's basic. I'm taking all the credit or blame, however you want to put it.
Hearing you say that, I kind of understand why we're nails on a chalkboard.
I don't think it's that. I think it's like the bits that we start with, don't you think? No?
Yeah, that's what I'm saying, is hearing you talk about whatever the hell you were just saying.
Well, that's not a bit. Wow. Okay, well, you know, we should move forward.
Today we're talking about mood stabilizers.
That's right. Giving the red meat to the audience, what people really want to hear. You can really see the reflection in the topics that don't really have much to do with medication, though. Who can blame you, right? The channel name is Psychofarm, after all.
You are withholding, though. We could have made this a tier list. People want tier lists.
I can't do a tier list every single episode. I just can't. That's awful. And I got to say, some people, non-regular listeners, I expect, come out of the woodwork for those episodes, those comments. They do attract the general public in a way that, you know, I'll take any view. I'll take any attention, but it's a little worrying.
Well... You know, I think a tier list would be nice here, but we don't have to do it. We can go non-tierless mood stabilizers.
That's right. And, you know, I'm not ruling out some kind of a tier list for the treatment of bipolar disorder specifically, right? Because it's too limited to do mood stabilizers for that. Unfortunately, we don't have quite as many mood stabilizers as we might like.
Yeah, and also people have been asking for a lithium solo podcast, so I hope that this turns into a solo lithium podcast eventually.
Yeah, I don't think we can fill a whole episode with lithium. You say that, we could fill 10 episodes with lithium, but let's do... This is it, this is the lithium episode, that's what I'm saying.
Okay. All right, I'll let you start us off.
Okay. Well, I mean, that really gets us to the number one mood stabilizer. To me, well, even before we get to that,
we should talk, mood stabilizers as a category is pretty confusing. And I also think, you know, when we have like the category of like SSRIs, you know, it's very clear that all the medications are very similar. Mood stabilizers is a wonky category of medications that are fairly different than And it's a simplistic grouping of these medications.
Yeah, it's not a good name, is it? Just like antidepressant is a good name. I struggle to find a better name that's pithy. But maybe a better way to call this class of medications would be anti-brain hyperactivity medications. Right. Or just anti manic depressive meds.
Yeah.
And that's but mood stabilizer is not good.
That's how I define it. So it treats or prevents episodes of bipolar without flipping someone into the opposite pole. Because, yeah, and that's the best. Because I remember being confused, like in residency, Nasir Ghani would be like, antipsychotics are not mood stabilizers. And like, it's a confusing thing because it's a linguistic turn of phrase that he's using there. Yes.
Yeah. And it's something I didn't really understand either until I started earlier in my career to make a greater effort to add mood stabilizers to antipsychotic regimens, even dual Antipsychotic regimens that people have been on for a long time. If you do that when it's indicated, you are going to find significant improvements in some patients that you just can't achieve using the antipsychotic class. If we drill down, it's because they do seem to have different mechanisms of actions.
That being said, the mood stabilizers themselves are each kind of unique. I mean, thinking about the A lot of them are anti-epileptic drugs. Thinking about the anti-epileptic drugs, I'm not a neurologist, but my understanding is they have so many different ones that are indicated in different types of epilepsies, right? So it's a class that's been grouped together because we use it all for the same wide grouping of pathology, but they're just not similar.
So it does get complicated.
Yeah. I think it takes a little bit of experience or reading from experienced clinicians to understand that whenever you're talking to a bipolar specialist, they emphasize the importance of mood stabilizers. And you'll see as you treat more and more patients, you start to use antidepressants less and you focus the mainstay of treatment on mood stabilizers, mood stabilizers, mood stabilizers. As you mentioned, if the overarching category And then a bunch of anti-epileptic drugs.
Vaguely, the other ones block voltage-gated sodium channels. The ones that I include, I think you might actually include more mood stabilizers in this category. But I consider it's lithium, Depakote, Lamotrigine, carbamazepine, and oxcarbazepine. I feel like we've talked in the past... You've talked about Gabapentin, and I think you might have referenced it as a mood stabilizer, but there's reasons I don't consider it a mood stabilizer.
It's not a mood stabilizer. I just like to remember it when I'm thinking of the mood stabilizers. It just doesn't have the effect of mood stabilizers. They tried it out, but it's just a relatively safe choice, you know. Except for the small amount of withdrawal and tolerance possibility. Think of it as an adjunct in the same category, but certainly not a solo medication. It just doesn't really work.
Just a few other points that I'd like to make. The big part about treating bipolar and what changes you from a novice to experienced in treating bipolar is focusing on maintenance. So the wins in bipolar is by improving a patient's maintenance and decreasing the number of episodes rather than focusing on... I don't know. You might help me word this better.
I'm going to say it's unfortunately indicated. It's rare for me to find a serious bipolar disorder that needs only one or two medications. Polypharmacy seems to be more the rule than the exception. This doesn't mean you should jump to polypharmacy, okay? But you shouldn't necessarily be afraid of it in the service of getting somebody better. That being said, there are a few simple bipolar disorder patients where you can manage with a single mood stabilizer.
So, you know, don't be afraid to try that for the first step.
Yeah, and I worry – I'm 100% in agreement. And then the caveat I want to place is make sure you have the diagnosis correct because I do fear by saying polypharmacy is the rule, not the exception, that we're giving permission to over-medicate personality disorders or have someone on lithium and Depakote and Lamictal when someone really needs to reassess the diagnosis. Or – Stacking more and more medications on a patient who does have bipolar and comorbidities that aren't being addressed.
Yeah, exactly. So prescriber beware, I suppose, but just know it's a complicated area. Yeah. So that brings us, I think, to the first and the gold standard mood stabilizer. It's lithium. It's the lithium episode, right? You gotta love lithium. And, you know, I should have said earlier, but particularly with lithium, mood stabilizers are probably the most underrated class of psychiatric medications on the market today.
Agreed.
They're not used enough. People don't give it enough of a chance. People aren't using it enough as an add-on in certain conditions. But lithium in particular, I think, scares people. And as a result, the prescription rate has gone down. And I think a lot of people are going without a really great medication for their condition because of all the different reasons why people are loathe to prescribe lithium these days.
Yeah, and I get it. I think it is scary prescribing lithium. It is your first time. You're like, oh, my God. I'm going to have to talk about all these labs and all these side effects and all these problems, and this person's hypomanic right now, and they're not listening to a word I'm saying. How am I supposed to prescribe this? And I actually – I know some excellent nurse practitioners who – Yeah.
Um, I'm
now thinking before we even talk about lithium in more detail, should we talk about the indications for mood stabilizers beyond DSM defined bipolar one and two?
Yeah, sure.
Okay. We'll make it quick. Right. Um, What people have to realize is that the bipolar 1 and 2 categories in the DSM have been created to give an adequately reliable sample set and definition of a specific manic depressive type illness that can then be used for studies and research and to be defined. But the DSM itself doesn't even believe And I believe that these are the only two types of bipolar disorders.
Look under the other specified bipolar disorder category. So do not be afraid to consider and use mood stabilizers. And frankly, I'm going to say you should use them in people who have sub-threshold These are, at minimum, the categories where I think mood stabilizers can be trialed, carefully at least, to see if there's a response. On top of that, the adjunctive treatment of the schizophrenia, do not be afraid also to use mood stabilizers.
We don't understand these categories as much as we think. And I think the reality is that there's probably a lot of genetic and pathophysiological crossover between the bipolar disorders and the schizophrenia and sometimes OCD, ADHD, autism. Okay. In those categories, when you are out of your standard options and there is a clinical need, you may consider mood stabilization.
Now, what do you think? I do see a lot of patients with personality components, especially with something like Lamictal, patients who come in with depression and say, because you mentioned the episodic depression, the Kreplin defined manic depressive illness, which wasn't defined by polarity, but recurrence of episodes. So there, if you see Yes. A significant family history of depression or significant family history of mania. I pushed lithium much higher in terms of my...
Yes. Yeah. And not quite Lamictal. I actually have found that in that patient, Lamictal doesn't perform quite as well. Yeah.
Like for the recurrent depression? Yeah, not as a monotherapy. Yeah. But I use it frequently on top of the lithium, personally speaking.
Yeah.
You know, we should also quickly talk about the practice, I think you kind of referenced it, of using Lamotrigine or other mood stabilizers for apparent borderline personality disorders. I'm definitely against that, personally speaking. I know some people are believers in that, and there's this tiny little signal from that old UK study. But I don't really believe in that. I think you really need to have at least some evidence of like a, you know, neurobiological type depression where there's episodes or stark changes in total functioning rather than simple mood or reactivity between human beings, interpersonal issues.
But, you know. I don't know everything. Some people swore by it. I would just be really afraid of putting people on unnecessary medications. And, you know, maybe we should do an episode someday on the pharmacological, quote unquote, treatment of borderline personality.
I think you also find there's someone out there touting the perfect use of like or that like there's someone saying like amphetamines fix the personality disorders or someone saying lithium fix the like. You'll find someone who says that every single class of medications is the direction to go. All right. Yeah.
I mean, you can always get surprised. I remember I had a patient who I thought was just stark raving personality problem. Of course, presenting in the context of having been force tapered quite recently from a benzo by the last psychiatrist that had seen him and I had to take over and kind of manage that. And I saw it as really just a, you know, benzodiazepine dependence and personality issue.
But over time, after that period passed, there was still reports of hard to believe total insomnia. And started Lithium. And he was like a different person afterwards. So that one was a surprise. And then on the other hand, a young patient presenting with Sort of classical report of DSM defined bipolar 2, right? Seemed pretty reliable, corroborated by family, but put her on lithium and no change, no change.
And then beginning to present to the hospital in context of, you know, seeing an ex and having a kind of a crash out there. Maybe not bipolar, right? You do have to update your diagnoses and pay attention over time. You can't just hang your hat on your first impressions.
Yeah, and that first story you told, I have almost the exact same story. A patient with incredible developmental traumas, lots of interpersonal issues, also what seemed like episodic mood episodes. I did the psycho ad of providing like, you know, I'm not quite sure if this is, you know, I'm leaning more towards personality and trauma. But if you want to take the lithium route and we saw spectacular results, life changing results, got his life together, finally was able to develop Stability in his life.
Really turn things around. So yeah, I think we all have that. You need to be open to updating your formulation. And like I said, working with the patient and describing what you're seeing and then giving them the options within certain parameters. All right, let's get to it. Lithium.
Well, yeah, that's enough of that. Okay. Lithium. Lithium. Don't be afraid of lithium. Don't be afraid of lithium. A lot of the side effects and problems are emphasized with lithium are, in my opinion, from the older era of prescribing, which is based on inpatient. And that goes the same for the practice of starting at around 900 milligrams total daily dose. Too high. Too high for the outpatient population, in my opinion.
So the first thing that I would say about lithium is that you should try it at And around 450 milligrams nightly on an ER. We can go into all the ins and outs about why ER or not, once daily or not. Do you want to do that? What do you think? Will people be interested
in that? No, no. Let's keep this a little bit more practical. And then if we want to get more theoretical and go into the research later, let's keep this practical.
Now, you're free to give lithium twice a day. If they prefer it, if you prefer it, if it works for the patient, that's fine. But just know that you don't have to do the ER twice a day. You can dose it all once in the daytime. But you're going to have to time your lithium level draws accordingly, which can be a bit of a challenge.
Yeah, so talk to me about how you think about dosing and then also when you get labs relative to the dosing. So you mentioned like starting at 450 at night, do you then get a dose right after or do you wait till you get to a higher dose?
So I think because we do have that training on lithium about having a very narrow therapeutic window, so they claim, people start to try to treat the level instead of the patient.
Let's not get sued. There's a narrow therapeutic window.
There is not a narrow therapeutic window for lithium. There's a narrow therapeutic window for lithium if we're treating acute mania. Okay, that's the key. That's the key. So when it comes to treating lower acuity conditions or in the long term, you can see clinical improvement, even if it's not perfect, with lower doses of lithium. And this is important because not everyone can tolerate the therapeutic levels of lithium.
There seems to be a pretty variable amount of adverse effects to different doses of lithium depending on the person. We're going to get into that later. But to answer your question, what I do is that I will titrate Up to the range of around 750 or even 900 depending on the reported adverse effects even without the first lab draw. But this is because I'm in a low resource clinic where despite my efforts many people will refuse or be unable to get lab draws for one reason or another and they have enough symptoms that the risk is worth it.
Okay, so at least me personally, I'll go up to around the 750 range before I get the first lab if they're still having symptoms and if they're tolerating the medication well.
Yeah, and I think it's important to emphasize it does depend on your patient population. I think if, in general, if you have a patient that absolutely you know is never going to follow up for labs, lithium probably is not the medication, the correct medication. If you think they'll intermittent I think if you know you're never getting labs, I think the risks outweigh the benefits. If the disease process is so high, then you're willing to forego the typical monitoring schedule.
Yeah, personally, I'm probably, don't tell the patients this, I'm willing to give up to 450 or maybe even 600 of lithium without labs in the long run if the patient is competent, has the capacity to understand the risks that they're taking on. Because again, I do think the risks are overstated and generally associated with the classical dosing pattern of lithium, where it was very high doses, right?
Again, starting dose of 900. So I think we need to differentiate between what are the most serious and talked about and feared side effects of lithium, the risks, and what are actually the most common things that you run into. Yeah. So everyone knows the scary stuff, right? Lithium toxicity. So make sure you talk to your patient about hydration, right? Salt intake because taking in too much salt will lower the lithium level and not taking in enough salt will raise the lithium level.
Being dehydrated will raise the lithium level and over hydrating will wash out the lithium. I usually use this opportunity to emphasize how this is a natural salt. People tend to like that, right? They like to hear that it is natural and it is. It's literally the element of lithium that's absorbable. And of course, warn about the signs of lithium toxicity. No NSAIDs. Not everyone knows what NSAID is.
You might want to tell them or just remind them that they forget they should talk to a pharmacist. And when it comes to the blood pressure medications, the ones that interfere with lithium, there's actually quite a few. And what I just say is you need to make sure you tell your primary care doctor or whoever prescribes you a blood pressure medication that you're on lithium. Now that's not foolproof.
I've had patients do that and then the primary care doctor will immediately prescribe a interacting medication for blood pressure and not give them any advice or change the lithium until the next time I actually see them and find out about it. So that's a little reminder of the importance of updating the med list for your patients.
Now, when you were talking about the hydration levels, I'm going to make it as simple as possible. You kind of just counsel patients, try to keep your hydration levels stable. Don't let yourself get too dehydrated. Now, this is going to sound like I'm plugging our website, but that's not the intention. Plug away. Yeah. One thing that I made that I did actually very early on that made me infinitely more comfortable with prescribing lithium is I made a little page sheet that I share with the patient.
And what I would do the first few times I prescribed lithium, and I still do this with patients that I feel like need to hear it. I share my screen and I walk through the, it's a Google Doc. And I walk through the Google Doc with the patient. So this way, it's not like I need to memorize all the things that you're saying. We kind of go through it.
And then I share it with the patient. And it also has their labs. So I say, like, I want you to take this and update the sheet with me and we'll keep it updated together. And then this way we work together towards updating. Keeping the blood levels all the same. It has all the information with regards to the major interactions. It has all the discussions in regards to the kidney risk, the thyroid risk, the parahypothyroid risk.
It makes it so that I'm not nervous during the appointment to remember all these things and we walk through it together.
Yeah, that is a good way starting out when, or even later, if you like, when you don't have it all down pat. You do it enough, you don't need the sheet anymore. But you're not going to not need the sheet until you use the sheet. And also, I made the lithium.
Lithium is the only guide that I made free because I think this is so important. So I made the little Google Doc that you can share with patients totally free on the website if you go to farm.
So along with the rare adverse effects that we're afraid of, then we get onto why we check labs. And I kind of hate that there are labs for this, okay? Because the fact is there are so many adverse effects with antipsychotics that there are no labs for, so we don't check labs. And then patients feel good about it. But when you tell some patients, oh, you need labs for this, they suddenly feel like you're using this super dangerous medication.
Well, it's really not it at all. It's that we actually can check the labs for this particular medication, so we have the privilege of doing so, but because of that, that kind of limits. It's lithium's use, even though it's a much better medication for numerous reasons.
Yeah, and I literally say that to patients.
But what are you looking out for?
Oh, no, I literally say to the patients, like the way I think about it is we don't do labs because this medication is unsafe. It's because we're doing this labs, this medication is extra safe. It's a small little flip that kind of makes it.
Very good. That's a really good way to put it.
Yeah.
So what do we look out for? We're looking for kidney function, right? We're looking for thyroid function, and we're looking for calcium levels. That's the simplistic way of saying it. Those are the main ones that we're going to see being impacted on labs. Now, you can also see demargination of the white blood cells and a little higher white blood cell count on lithium. That is fine. Don't worry about that.
It's non-pathological.
Yeah, and the truth is, as you say, the way I talk with the patients is we know that lithium kind of degrades the – over time can cause problems with the kidneys and the thyroid. So what we essentially do is we keep monitoring it. We check it all the time, and we make sure to see that those levels aren't going down. If those levels are going down, that's okay.
We can plan then what exactly we're going to do about it. The one thing that's super helpful, I forget the exact statistic, but it's like the 20-year actual risk for renal dysfunction when you're not using it at the manic doses is much, much tinier than everyone is aware of.
Yes. And even if you have guaranteed decline in renal function, that is not the same as renal failure, okay? And if you told me that over the next 20 years, I had the choice between 30% worse kidney function and 30% less brain function, I'll tell you this. I'm going to take the better brain function every single time, and I'll pay for it with my kidneys, personally speaking, okay?
And I tell patients that, and it's true. But everyone's a little different, and some people don't want to accept it. So if they don't want to accept it, you don't push the lithium. You move on to the next choice.
Correct. And what you do see is for patients who lithium works, it's not a question of how bad the... Patients with true bipolar, when they're stable and lithium works, there's no question of whether the... They're willing to do... Yeah, it's so
worth it. It's completely worth it. Okay, those are the rare things. What do we actually see? What are the two major adverse effects in my experience with lithium? It is thirst combined with increased urination. Not the same as diabetes insipidus. That can happen. It's more rare. And then acne. Okay. Those are the two major ones. Weight gain is possible, but to be frank, I don't see a whole lot of it.
Maybe because I don't dose a lot. I think if lithium is one of those where I do think there could be flattening on too high doses and slowing. Kind of like the antipsychotics, even if they work differently. But if you're dosing it appropriately and at the minimum effective, then you're not going to see much weight gain. But acne, unfortunately, if it happens, there's not really much you can do about it.
That's based on my consultation with dermatology. They can give all kinds of topicals and medications, but it seems to be its own mechanism. Some people are fine with it and they can live with it. Some people, it's not going to work and you're going to have to switch. And the thirst issue does seem to be dose dependent. Sometimes people tolerate it better with nighttime dosing. Some people tolerate it better with daytime dosing.
But one wrench in the works here is that it does cause thirst. You're taking in assault. So sometimes it's because people are taking in more liquid, okay? Sometimes with all this talk about hydration, when you first prescribe the lithium, people take it upon themselves to actively change their amount of water intake. I think I want to be clear to patients and say, you don't need to change what you're doing, but talk about any changes you notice at the next visit.
I do want to comment on what you said with regards to the acne. So you mentioned that there's no option. There are options that do work. The issue is that they have very serious interactions with lithium, but they're not completely contraindicated, but for patients that it severely impacts And they understand the risks and they're a compliant patient. The two options I'm thinking of is spironolactone, which we know increases lithium levels.
So it is an option if you have a very compliant patient that you can check labs, check labs before the dose, the start of the spironolactone, check labs after the start of the spironolactone dose. The other option is now I'm seeing more derms. I've had more patients that they're now prescribing Accutate more and more. Obviously, that's very scary because there's black box warning with regards to, I forget specifically what it is, but it can cause mood instability and suicidality.
Suicidal ideation. But that said, it's not 1000% contraindicated. And if the patient fully understands the risks, they're well monitored, they've got good family support, you've got a close eye on them, it's not completely contraindicated.
Yeah, I guess it's a thing that just doesn't really come up for my population. If they care enough about the acne, they're not going to take those risks and try these outside Accutane a game changer. The drastic difference. Is that really the lithium being treated or is that just an underlying acne problem being treated? I'm not sure. I'm not a dermatologist. Speaking of unusual things you can do to treat side effects of lithium, there is ameloride.
Technically, that has been written about and has some small case studies about where you add that with lithium and it reduces the amount of damage that lithium can do to the kidneys and also reduces the polyuria. So that is, again, something I don't do and I wouldn't be comfortable doing unless there's more evidence-based, but it's not unheard.
Yeah, and also a good option for the blood pressure medications. It is a decent option there.
Yeah, something that I would definitely discuss in conjunction with a cardiologist or at least an internal medicine doctor if we're going to do. And then finally, the diabetes insipidus issue. The way you're actually supposed to tell if this is really happening or if it's just simple polyuria from lithium, which is, by the way, the most common adverse effect of lithium, is that you're actually supposed to do a 24-hour urine collection study.
I have no idea how to order that at a psychiatric clinic. I don't even know if people are doing it all that often in an internal medicine clinic. Personally, if I'm hearing about so much urine output change, you will get increased urination. It's not going to be anything crazy. But if you're getting liters of increased urination consistently after lithium prescription, I would just... Maybe start considering changing it, especially if you haven't tried alternatives.
It's a good call. One thing I want to mention. Anything else? Yeah. Ordering labs is not as big a deal. It's not as time intensive as I once imagined. It's not like you need to go on a website and fax things and all these things. You can make a lab requisition form and give it to the patient. It's very simple. It's not time intensive. Don't be scared of ordering labs for patients.
It's very simple.
Oh yeah, lab levels. You know, again, for lithium levels, treat the patient, not the level. So go off of your actual long-term clinical stability or lack of stability. Look at the sleep patterns carefully. That being said, I would consider for the... Adjunctive treatment with lithium or for mild bipolar, anything in the 4 to 7 range is actually fine. You don't have to do the old manic dosing.
But yes, there are people with more severe bipolar 1 where you're going to definitely want that Yeah, why don't
I give the standard teachings and then we can give the clinical experience teachings. So it's usually maintenance is considered the 6 to 8 range. 8 to 2 is considered acute mania. Now that doesn't mean that you're protecting mania. That means the patient is actively manic. That's when you push up to 8 to 2. Actively manic patient. The mania breaks. They're doing better. Bring down the dose. The patient should not be stuck unless you have clinical reasons to do this.
Patient shouldn't be on 1 as a maintenance dose. You should then bring them down to 6 to 8. For treating depression, you can get away with even lower, the less than 6, 4, 6 technically. But as you said, the most important thing is treating the patient in front of you, not following these labs perfectly.
Be very careful when you lower lithium though. Among the mood stabilizers, abrupt lowering of lithium or stopping the lithium may be more likely to even induce mania rather than simply unmask it. That's one thing to keep in mind. Also, like the rest of the mood stabilizers, Stabilizers, the onset of effect of lithium takes at least two weeks most of the time. So that's the problem with the mood stabilizers.
I think that's why a lot of people don't use them today, because they want instant gratification as a clinician and a patient. You have to set expectations. This is a benefit that comes over the course of months. And yes, even after those first four to six weeks, I do see continued improvement in the mood overall. Stability, ability to enjoy things, treatment of both depressive, manic And
I think you nailed the big thing that when you're talking with patients, the psycho edge you provide is so important. The mood stabilizers decrease the number of episodes. Yes, it helps with depression but it's very slow. Yes, it helps with mania but it's pretty slow. The reason why I find treating bipolar so fun is because you say we're playing the long game. We're trying to decrease the number of episodes.
We're trying to make it so that you live a fulfilling, happy life. We're not treating the symptom of the day. To me, it's so important to have strong relationships with your bipolar, with all patients, but the relationship and the psycho-ed is the most important in something like bipolar.
Yeah. And, you know, another, speaking of long-term benefits, don't be afraid to maybe sprinkle in the suggestion of the anti-dementia effect of lithium. Obviously, this is not subtle science, but I do think there's enough evidence so far to at least mention that this seems to be something that is a positive effect of lithium in preventing dementia. Especially in bipolar disorders. And I do also think that preventing both depressive hypomanic and manic episodes seems to be beneficial for changing the disease course of people with bipolar disorder.
Otherwise, you kind of get an acquired ADHD if you don't treat those mood episodes early enough. Their cognitive functioning seems to decline. Yeah.
Why is this not a full lithium episode? Let's go on to the next medication. We have, I have so much more to talk about, but we're 40 minutes in.
Yeah. Well, luckily there's not that many mood stabilizers. Let's do Depakote next. It's the big boy. Everyone loved Depakote in the 90s. Personally, I think that, I'm sorry, we should say valproic acid. I think that valproic acid is a little overrated. I agree. I don't like Depakote as much. I think a lot of people like it because the
The, um, the blood draws, you don't have to do as many and it's much simpler. Um, so it's a lot easier. I feel like to, and for some reason there's just less of this, like, oh, there's the kidneys and all these things. It's like, oh liver, but it's fine. It's not that big a deal.
Um, Yeah, I mean, let's face it, high levels of lithium guarantee you decline of kidney function. High levels of Depakote do not guarantee any end-organ dysfunction necessarily. You've got to monitor for it, but it's not a guarantee. You're pretty much looking out for a low platelet issue. Hyperammonemia, the liver producing too much ammonia. And that's most of it that you look out for on Depakote. I mean, there are some rarer things like changes in your blood counts overall.
But yeah, Depakote is a little simpler. But I don't like it. Why? Well, it doesn't... Substack, Substack, Substack. Also, with all the reports on the effects on fertility, now male fertility, and as we know, on fetal development, I don't love Depakote personally, but it's easy to use.
I think the fertility thing, I had an attending who would use it for all patients, and it bothered the heck out of me. A lot of the patients, when they're first presenting, they're in the 20 to 35, the 20 to 40 range where they could be considering having a child. Exactly. Why would you start a patient on a medication that in the next five years, next 10 years, you know that you're going to have to taper them off?
The valproate, the The teratogenicity makes it so that women absolutely should not be using it, period. And if you have a woman who's on the medication, you pretty much have to taper it off if they're talking about pregnancy planning. Now, I think it's in Europe. They have a warning for men as well. So why would you start a patient on a medication that you know is going to have to be extremely disruptive during the time when you want the most stability right before you're in, you know, parent plan, like long-term family planning?
You don't want to be tapering off a mood stabilizer just as a prerequisite to considering having a child. That's crazy. Yeah.
Yeah. Now, if they are child-free in philosophy and they're on birth control as well, then I'm much more comfortable with it. Okay. Who else do I consider Depakote for? There are some special cases where I feel like it's a little bit more indicated. Significant irritability and aggression. There is some clinical wisdom that helps, and I do believe there is some effect there. People with a legitimate migraine condition, Depakote can help prevent the frequency and severity of migraine headaches.
So that's a good one. As an aside, we might actually want to avoid lithium in people with genuine migraines. Not just headaches, migraines. Because it does seem to likely worsen the migraines in a lot of people. So you might want to consider screening. Finally, people with history of TBI-induced neurocognitive or mood changes may benefit from lower levels of Depakote even without the bipolarity. So when you have the comorbidity, I don't mind giving the Depakote there.
I guess even talking about the patient that's going to historically respond the best to lithium is the idealistic bipolar patient, the patient with euphoric mania and then with intermittent episodes of depression. That is considered the idealistic lithium patient. Depakote has some evidence with rapid cycling. It has some evidence with mixed episodes. And as you mentioned, like the irritable dysphoric mania.
Yeah, personally, I acknowledge the evidence-based that suggests those subtypes and those matching medications. We feel the same. I don't really subscribe to it. I feel like it's selection bias, yeah. But then when there's added-on effects and indications like migraines that we can prove, then I'm like, yeah, let's go for
it. Should we move on?
I think we should move on. I don't love Depak.
All right, so we're going to Lamotrigine.
Lamotrigine. Boy, I love lamotrigine. Unfortunately, its anti-manic efficacy is not fantastic, but its relatively robust antidepressant effect for bipolar depression, pretty great. I know the studies show that it's not effective for treating acute depression. I'm going to say my clinical experience contradicts that. Okay, that might be because I often use lamotrigine in combination of lithium. I don't know. And also a bunch of other things I'm doing from session to session.
But just don't be afraid to use lamotrigine. The biggest side effect and problem is, of course, Stephen Johnson syndrome.
Ian, the thing that's great about lamotrigine is the side effect profile. And I think it's really important to think about what can a patient tolerate? If a patient is on a medication that isn't causing major side effects, isn't causing major problems, they're more or So, Lamotrigine is a great option to help with added stability. It mixes well with lithium. Patients tend to like it. So, as you mentioned, no anti-manic So it does help prevent the episodes of mania.
But if a patient's manic or hypomanic, it's not going to work. So the best way to think of it, all these medications typically is you're preventing episodes more so than stopping them. But I agree with your point and with regards to the depressions.
Yeah, it is, as you say, it's the most well-tolerated mood stabilizer by a long shot. And frankly, I like to phrase the SJS risk because of its rarity as an allergic reaction. I know that's not scientific, but from a phenomenological perspective, it's about as rare as a just fundamental allergic reaction to some new medication, right? And that does mean that if you're not seeing the SJS upon the initial protocol challenge, it's pretty dang unlikely that you're going to get it in the future.
But you should follow the rules. You should absolutely follow the rules. Do not titrate. You'll see a slower titration schedule depending on whether you're dosing the same time as an inhibitor of its metabolism, like Depakote, for example, or with other considerations. But follow that protocol and warn, warn, warn. What I usually say is, are you prone to rashes? If so, what kind of rashes do you usually get?
Okay, this person has eczema or this person has psoriasis. We're talking about a rash that is new and that you haven't had before and that's different. If you get any new rash while we're starting this medication, I want you to stop the medication and go to the ER. That's how I do it. Do you have any personal approach to the SJS talk?
Yeah, I'm going to talk about it. So... With the rash, this is psycho at a point that you absolutely cannot miss. Now, being in New York City, it's hard because a small rash going to the emergency room as a clinician, it's scary because there's a decent chance they're going to spend a ton of money and they're going to get stuck there for 12 hours and then they're going to get told the rash isn't a big deal.
Unfortunately, we can't fix our broken healthcare system. Even if we want to protect patients from terrible emergency room visits, you know, things that take a lot of money, that doesn't mean that we don't recommend the correct thing. And so I think that's important in that, like, don't be like, you know, the rash isn't that big a deal. Like, why don't you, like, you have to still give the proper responses, even if the system behind you is not built to appropriately respond to it.
Now that you're talking about it, if I had a higher SES population, I might add something to that and I might say, if you can get a same-day appointment of a dermatologist, you can do that too. Because to be frank, they're actually going to know a lot better than any emergency room doctor about whether or not it's SJS. So that's actually the better option if you can do it, especially these days with telehealth.
And frankly, if you've got cash paid dermatology, they might be able to squeeze you in. But for everyone else, unfortunately, it's ER. Would you accept urgent care? It doesn't happen very much. Yeah, yeah. I'd accept urgent care with the caveat that the urgent care has to know what they're doing. So you might want to warn the patient that, you know, your experience may vary. But fundamentally, the frequency of any rash, let alone SJS, happening on Lamotrigine is so low that most of the people you started on are not going to run into this problem.
But just keep in mind, East Asians and I think maybe Indians? People from India. There are ethnic groups that will have a higher risk of SJS, Steven Johnson syndrome, to lamotrigine, oxcarbazepine, carbamazepine, those kinds of things. Okay. And there is testing available to see if they have the gene that puts them at particularly high risk. The name escapes me right now because, again, for my clinic, they don't have access to that testing.
HLA-B15? It's HLA-B something. That's my guess.
Is it? 15.
Okay, maybe 12. It's HLIB something, one of the numbers. If you Google it, it's in the FDA package insert. It's actually recommended to test before, I think, carbamazepine. That's correct.
If you have an Asian patient, FDA recommends testing for the HLIB 15 for carbamazepine.
Yeah. Two more points about Lamotrigine. Don't linger on lower doses, in my opinion. If you're going to use it, get it to 200. It's so well tolerated, okay, and you get benefit. But also, don't be afraid to go above 200 either. You can technically go to 400. I don't do that with any regularity. I rarely, rarely, rarely go above 200, but it is possible because people do metabolize.
Stabilize it differently. Keep in mind also, pregnancy will reduce the serum levels of lamotrigine by about half. I believe it's estrogen that does this. So anyone taking a oral contraceptive as well will notice technically increasing levels of the lamotrigine in the system during the placebo week if they have a placebo week on the particular format of contraceptive pill that you're taking. But that's usually not clinically relevant.
But you've got to know about the various... You know, metabolism interactions.
Other big interaction with lamotrigine. So valproic acid jacks up the levels of lamotrigine. So the way I remember it is when you combine those two medications, it's the dangerous interaction. So increasing lamotrigine is what we're scared of because of SJS. So whenever you're interacting using those medications, you should half the lamotrigine. Look up in your prescriber guides what to actually specifically to do.
If you're ever trying to do both of those at the same time, I don't recommend it because it's a huge pain. Be careful and review the protocol carefully.
Almost exactly opposite what I said at the start of this. Lamotrigine is a great mood stabilizer, but if a patient is super anti-side effects, that doesn't mean that we don't recommend the proper stuff and we just keep them only on Lamotrigine. There are a lot of patients that, you know, the heavier So, yeah, sometimes I worry that medications without side effects like lamotrigine and bupropion, people will keep patients on and then not offer what the correct treatment is.
And patients are fine with it because it's like, oh, no side effects, great. But, you know, when we're talking about serious disease burden, we're really measuring the scale of risks and benefits. And for a lot of patients, the The benefits of the other medications outweigh the risks.
Yeah. And touching back on what we mentioned before about polypharmacy, this is, again, a situation where polypharmacy can actually help. A lot of people can get away with having a lower daily dose of lithium if they're on their 200 of lamotrigine. And then it'll be much more tolerable than trying to do just the lithium, for example. My answer to bipolar disorder is mood stabilizer. My answer to bipolar disorder not responding to one mood stabilizer is not antipsychotic.
It's two mood stabilizers. So do not neglect the mood stabilizers.
Yeah, the wonderful Dr. Phelps, who... Probably at this point will be the episode before or after. He emphasizes how great it is to use the motor gene, which doesn't cause a lot of side effects, and then use lithium at lower doses that are typically used to avoid side effects. Of course, it depends on the patient, but minimizing side effects is going to increase tolerability. Should we move on to our next food stabilizer?
Yeah, we should talk about carbamazepine, which I never use. I literally never use carbamazepine, so I'm not going to be able to say much about it. Why don't I use it? Well, it's got too many drug-drug interactions, interacts with like a billion different other medications, and it interacts with itself. It's got a personality disorder. I hate it. So it takes forever to get to level. I don't care if it has a bigger evidence base.
It just sucks. So it's not that efficacious in the first place. I don't use it personally. Problems in self and
problems with others. Yeah, exactly. Yeah, as you said, like, so it causes SIP3A4 induction, and then it causes auto induction. So it's just, it's really problematic with regards to drug-drug interactions. There's very few patients that you can't justify a different medication rather than using carbamazepine.
Yeah. And so you'll have to turn to a fan of carbamazepine for more information about it, personally speaking. That leads us to oxcarbazepine, trileptol. Now, every time I write about this medication online, there's like a cavalcade of people criticizing and saying there's no evidence for it, it doesn't work, blah, blah, blah. I think they are saying that because they're not using it enough. OK, you have to actually try to use it.
And if you treat enough bipolar disorders, you're going to know that some people don't respond to one mood stabilizer and respond to another. I've had people not respond to lithium. OK, that happens. So there's no guarantee that just because it's a mood stabilizer, it's going to work on your particular patient. And oxcarbazepine is no different. Is it probably less efficacious than Depakote, Lamotrigine, and Lithium? Probably. But I also think that at higher doses, it may actually be more efficacious than Lamotrigine.
If it's the right patient, it's actually not that bad. In terms of adverse effects and tolerability, the only real downside is that you do have to give it at least twice a day, in my opinion.
Yeah, not that I feel like it's easy to pretend like I know biochemistry more than I actually do and make pretend that I understand how that actually impacts patients. It is so chemically similar to carbamazepine. It literally is just like one little oxygen. It's like the only difference. And listen, any psychiatrist who pretends without a PhD in biochemistry, like we know what we're talking about, we don't.
But the fact that it's so dang similar makes me feel like it's the evidence in regards to how it works is probably pretty similar to carbamazepine. And we know that studies, there's a lot of like randomness. It depends on the patient population that's studied. There's so many different like little caveats that if they didn't want to pursue it for a particular indication, they're not going to run tests on it.
So to me, it intuitively will have the same similar evidence base to carbamazepine.
Yeah, I mean, there's probably a bunch of other anti-epileptic drugs, anti-seizure medications that work for bipolar, but we're just never going to know because they have no motivation to test these kinds of things and we have no motivation to use it. It reminds me of a patient I once had, you know, she had clear evidence for hospitalizable bipolar disorder in her early 20s, you know, the typical onset.
And then, starting around the age of 30-something, just stayed out of the mental health system for about 20 or 30 years. And then I was seeing her as the first psychiatrist that had seen her for 20 or 30 years for some new trauma. And I was like, what happened with that bipolar disorder? And she's like, I don't know. Okay, well, let's talk about the medical history. Any problems?
Oh, yeah, I developed seizure disorder in my 30s, and they put me on Keppra. And I've been on Keppra ever since. And I was like, well, that's odd. That's the only thing that I can think of that would explain why you stopped having mania and hypomania. I was just like, I don't know. And then I looked into it, and there's at least some case studies. Even though Keppra is well known for causing irritability in some patients and worsening anger outbursts, apparently it may have some anti-manic effect.
At least there's some evidence for it in some patients. So my point here is that there's a lot we don't know. And I think to just blanket say Trileptol, sorry, Oxcarbazepine doesn't work for Armenia is ludicrous.
Yeah. And, you know, in terms of like the mechanism of actions, these medications, it's comical how little we know about it. Like I. I'll say sodium channel blockade, but the truth is I have no idea. And to me, it's just intuitive that anything that's going to decrease the risk of seizures is going to decrease the excitability in the brain, which is going to have likely impacts on something like bipolar disorder.
So to me, it's almost intuitive that something like... Theoretically, if you wanted to be a... Oppositional, we could say that maybe she had temporal lobe epilepsy that was being treated by the Keppra. Yeah, exactly. The truth is, anything that's going to decrease the excitability of the brain, to me, intuitively, it makes sense. It's going to have some impact on bipolar.
Yeah. And speaking of which, maybe just a quick appendix before we finish on not Mood stabilizers, but can be kind of thought of in very specific scenarios. wait, did we talk about
just check for hyponatremia? I feel like that's the only thing.
SJS, same SJS risk. You can't tell if it's higher or not because they don't use oxcarbazepine as much as lamotrigine. Lamotrigine is used so much more that is then associated with a lot of SJS cases. But because they are not used at the same rate, we can't tell Which one's higher risk or not? And so the same risks apply. Just warn about it. You don't need to get levels on oxcarbazepine, but you can.
Some people do that. I don't find that very helpful clinically. And yes, like most of these anti-epileptic drugs, look out for changes like sodium or
What were you saying about the non-conventional mood stabilizers, quote unquote?
Oh yeah, the appendix. Well, we talked about Gabapentin. They tried it in the 90s as a direct bipolar treatment as adjunct. They couldn't really get evidence for it. And yeah, I used it. I have been using it very enthusiastically as an adjunct for several years. Relatively low risk in my environment where people have access to much harder drugs on the street. But is it really efficacious for true bipolarity?
Not really, but I think it's a nice option as a sleep support medication and anxiety support medication in the context of trying to truly treat with a mood stabilizer. What else? Benzodiazepines. As a method of last resort, there is no doubt that scheduled benzodiazepines work on mania and bipolarity. Let's keep benzodiazepines out of here.
Let's stick with the mood stabilizers.
Well, no, no. I do think they are basically a mood stabilizer. They function to reduce the excitability of the brain. It's just that they're a full shutdown medication, and it's not good for those reasons. But when you see catatonia, you should probably be using it. Okay. I'll add lithium, too, because catatonia is more frequently seen in mood conditions. But, you know, you may need some kind of a scheduled benzo.
Tope. One final adjunct that probably shouldn't have been mentioned then with the, you know, a lot of woo-woo stuff going around these days, people are going to be angry I even mention it, but there is the theory of ketogenic diet.
Oh yeah, absolutely. I think we should stick with medications because if we're going to bring ketogenic diet into it, we need to bring light and all these other things.
That's true. That's true. Yeah. Well, then we won't get into that. Okay. I don't know if this answers most of the introductory questions. Information or questions or wonder about mood stabilizers. I wonder if there's anything that people wanted to hear about that we didn't talk about today.
Yeah, and then my, again, the plug is for pharm. If you're scared about psycho-ed with regards to these medications and risks, you pull up the patient guide, you share your screen, and you walk through the side effects and the risks and the monitoring with the patient. It is helpful.
All right. Well, I guess that's it for today. Until next time. We should have done a full lithium episode. Have a good one.