(Almost) Everything You Could Want To Know About Lithium

Preston: [00:00:00] It's the reason why I'm doing this whole episode. I love lithium. I think it's a good truck. 

Margaret: I think the thing that comes up when we can't do lithium is use of it in an illness where being able to like go get troughs and like get lab levels and keep someone in the persnickety window of lithium, like depending on how sick someone is.

I think that part can be a limiting factor in how good it is as an agent.

Preston: And welcome back to how to be patient. Or we have another pressed in episode in store for you. So strap in or lock it down, whatever you do to stay in your seat, including you, Margaret, because we've got a wild lithium ride ahead of us. 

Margaret: I'm looking forward to it. I listeners, let us know if you like these differently like LED episodes because we like them.

Preston: Do they? I know. I know they like them. They don't have an option. 

Margaret: Spoken like a 

Preston: psychiatrist. 

Margaret: I'm sorry to [00:01:00] redact.

Ugh. 

Preston: Yeah. Coming off, like, we spent the whole last episode talking about how evil psychiatrists were. Yeah, yeah. Guys, if you, we like them, so if, if you enjoy 'em, we're gonna keep doing them. And if you don't like them, we do it for us anyways. You know, that's, that's why we do the podcast in the first place that's called, it was always for us, that's 

Margaret: called service, customer service.

Preston: I, I just had this realization the other day, um, and I made a, a post about it that even if I was like, making enough off of like TikTok or this podcast to like, leave my, my main job, I don't think I would want to, like, I would hate just being dependent on content. Mm-hmm. Having your full-time job gives you the freedom to say what you want to say and create in the way that you want to.

Like you, you have permission to make bad art because you don't need to depend on it for your livelihood. 

Margaret: Yeah. I mean, I, I think, like, I wonder [00:02:00] how I would, if I was in a career where I like, truly hated the career, I maybe would feel differently. But yeah. I think it's so much pressure on your creativity or on, especially 'cause so many people start making content for fun, that it's like, unless you hate your job or you get so famous or so successful that it's like impossible.

Some, for some reason to do both. 

Preston: Like Brittany Broski that happened to her, right? 

Margaret: Yeah. But she also, I don't think loved her job. She like, she worked maybe in finance, like at a bank. Mm-hmm. Brittany Broski, if you hear our podcast. 

Preston: Yeah. Trailblazer. Trailblazer, 

Margaret: Dr. Kombucha. Girl, if you wanna talk to some mental health professionals, let us know.

Preston: Yeah. That, that, I understand that. Like I'm also in a privileged position, like in medicine, you know, really stable job most of the time it's rewarding rather than like corporate America. Yeah. Which, which may be more soul sucking than the content grind. I, I think my ultimate point is just if you wanna get someone to hate their artwork, pay, pay them for it, [00:03:00] you know?

Margaret: Yeah. Yeah. I think that like, I, but I, I also feel like sometimes people who make content, like they don't actually, like the thing they're making are talking about. And like, I think I made a video about this last, this week also of just like, why am I trying to make vi like prior I've been trying to make content, but I'm like, sometimes I like watching it, but like, I hate filming myself, like 

Preston: mm-hmm.

Margaret: Doing a routine or something. And I legitimately, I like creators like that, but I hate it. Like I actually hate it. I'm like, this is so, and it's not an insecurity, it's just like, this is intrusive to me. Like, I just wanna wear whatever pajamas I'm wearing. I don't wanna feel myself waking up. 

Preston: Yeah. I, 

Margaret: yeah.

Preston: So much to film those routines. Like I, I try to make these like coffee videos and honestly like it's a calming ritual to make my coffee and it's totally disrupted when I like try to film every part of it. I'm like, oh, like I feel like I'm chopping up my life [00:04:00] and trying to sell it to someone or yes.

Where I'd rather just, I think experience my life. 

Margaret: Yeah, it does feel like that. I also realized that like, I like those videos, but none of them ever stick with me. Whereas like people talking to camera who like have interesting things to say or like a totally different job background are like my favorite videos that I like go back to and I find myself thinking about like two weeks later.

So I was like, why am I, what am I doing? Like why am I trying to make humans 

Preston: like human stories? Who would've thought plain found in the sky? 

Margaret: Crazy. It's crazy. And I was like, what am gonna talk about? It's like I have 10 years of education. I could talk about how about the fact that no one can see a child psychiatrist regardless.

So I could talk about that. 

Preston: Yeah. We've got lots to talk about. Well, today's a preceded episode and I. Did not make an icebreaker. I just tried to like ease it in there by, by sharing at the beginning. 

Margaret: Yeah. Which was, you know, bold as We've never actually had a conversation off camera listeners. 

Preston: Yeah, no, this is the first time.

Um, how would you 

Margaret: rate it? 

Preston: Pretty [00:05:00] good, you know, nailed it. I like it so far, but if there's anything that I'd wanna stabilize my mood, it would probably be some lithium salts if I just had to guess, which is the topic of today's podcast. Everything you would ever possibly need to know about Lithium, which that's a pretty, that's a pretty lofty goal.

I don't think we're gonna get to all that, but I really tried and I, and I had a lot of fun, deep diving into everything I could find about lithium and, and telling its story. 

Margaret: Amazing. 

Preston: So, are you ready to begin? 

Margaret: I'm, I'm ready. Play the like. Welcome to the Charlie Chocolate Factory Music Editor. Here we go.

And we'll get copyrighted. Don't do that. 

Preston: So long ago in a galaxy far, far away, there was a big bang. That's where we're starting. 

Margaret: They're starting there. 

Preston: The universe began. Yeah. 

Margaret: Great. 

Preston: So some, there was actually theorized, some lithium that was first created in [00:06:00] the Big Bang, but a majority of lithium comes from stars.

So I want to tell you about how we make elements. Don't laugh. This is important. We're we're talking about the genesis. I didn't even audibly 

Margaret: laugh. The listeners who are only listening won't even know your 

Preston: audio. She's smirking at me right now.

Margaret: I'm so serious. I'm ready for seriousness. 

Preston: So when you think about the chemistry of the universe, there are basically protons, electrons, and neutrons. So the most simple thing you could have is just one proton and one electron sitting, floating around. Just basically the one, it's like, it's like the single Lego piece building block, that's hydrogen, right?

So we have a ton of hydrogen hanging out and hydrogen has gravity and we have billions of years from them to slowly coalesce. And then when you get enough, hydrogen is big gas cloud together. You get so much weight that the hydrogen on the inside starts to push into itself and then [00:07:00] it makes a two. So you get two Lego pieces to combine, and that's nuclear fusion.

So let's say you make helium, right? Because helium has two lithium S3. So are we gonna get there? That's kind of tough. It turns out that that's not that simple. That ball is 

Margaret: a choice. 

Preston: So as these gas balls compress and they, they cause this nuclear fusion reaction in the beginning, that that creates a huge explosion.

It's like a nuclear bomb inside of it. So you have gravity pushing in, you have, you have nuclear fusion pushing. It's a ton of heat, and that's functionally what a star is. You have, um, nuclear fusion hydrogen to helium inside most stars. So that's kind of going over time. But then as the force keeps compounding, you start to run outta hydrogen a combine.

You turn the helium like two plus two, you make a four, and then you make it eight. Then you make it 12. So as you get carbon and other of these like various compounds until you get up to iron and then iron no longer undergoes nuclear effusion. [00:08:00] So it just kind of becomes this like dead cold rock inside of the star.

And that that iron rock kind of keeps expanding and all of a sudden we have, um, an unequal distribution of forces. So that nuclear explosion is happening in the middle. It's, it's getting a lot weaker, but the gravity on the outside because the mass, this whole thing isn't changed. The gravity outside's pushing in just as hard as it was before.

And eventually the scale tips, the gravity pushes all the way in and the whole star collapses on itself. And then, and then you expand everything. So you start with a black hole that turns into a supernova basically. And in that reaction, that's when we make all the other elements or a lot of them. So that's actually where lithium can be made in these like supernova, black hole explosions.

Margaret: Got it. 

Preston: There are other times where there'll be like some galaxies where you have like two stars circling each other and as they like, [00:09:00] almost like do this dance, you get these runaway reactions on the surface. And that creates a lot of lithium too. 'cause you have these kind of like incomplete, like one plus two, two plus one, and those make those three proton compounds, which is lithium.

Margaret: Gotcha. 

Preston: So then all this lithium dust is in the air, explodes after these supernovas. And then the dust, just like the hydrogen has gravity, it collects into balls which become planets. That's Circle Suns. And then fast forward 6 billion years, we now have Earth with a ton of these weird different minerals inside of it.

And there's a lot of lithium that's deposited in earth. So where do you think we find lithium on the planet?

Margaret: Like what country? Or like what landscape? 

Preston: Either or. 

Margaret: Um, I don't know. Country, lithium. I assume it's in some rock somewhere. Yeah. Hell 

Preston: yeah. It's in a rock. It's non trees. 

Margaret: We're [00:10:00] listeners, we're again, outside of my interest. 

Preston: Yeah. 

Margaret: Preston's. Like we're gonna do a ge 

Preston: I'm, I'm speed running the physics 'cause Marcus just like staring blankly at me.

Margaret: I'm trying not to.

Okay. Is it? Yeah. So we, we have these cas. SAG mites are tight. 

Preston: Yep. Mites, lag tights. This is like, 

Margaret: when I was on a surgery rotation, they asked me what the, like suture was made of, and I said, wool, 

Preston: like kinda, 

Margaret: they're like, no. And they, they all laugh, but anyway. 

Preston: Yeah. That's good. Okay. 

Margaret: Where's the lithium? 

Preston: So yeah, it's, it's in these, they're called pigite deposits and it's in these like sedimentary rock in a lot of wells actually.

So, 

Margaret: so well water all these, a lot 

Preston: of natural hot springs will contain lithium and this Hmm. This becomes important later. 

Margaret: Yeah. Yeah. 

Preston: So the primary countries that, that do produce lithium and mine it from their, like sedimentary rock or these pigment [00:11:00] deposits are Argentina, Canada, China, United States, and Brazil.

So it's, it's kind of all over the place. There's no like ring of fire or like colliding tectonic plates that they find all the lithium in. 

Margaret: Okay. So. 

Preston: All, all that being said, lithium does have some interesting chemistry that will also breeze through. 'cause I know Margaret doesn't care about this, but I care about it.

I 

Margaret: do not care about it. I just like, I don't know what you want me to say during it. You're like, here it's, and I'm like, I, yes. It feels like I'm reading a textbook chapter, so I'm like, I agree. I'm nothing to add. I 

Preston: concur. So, um, lithium has, it has three electrons and you remember like those orbitals where it's like electrons like to be Paris one s two two 

Margaret: S two.

Preston: Yeah, exactly. Yeah, I remember that. Ones two, two s one. And there's nothing, electrons hate more than being alone. So it's, so it's super unstable with that two s one. Mm-hmm. So all it wants to do is get rid of its electron. Mm-hmm. And it does, it's so violent when it does that, that if you throw lithium into water where it can [00:12:00] discharge an electron, it will immediately burst into flames.

Hmm. Just like, it, like doesn't have time to start, like slowly burning or anything. It just like explodes. 

Margaret: And how is it in springs? 

Preston: So that's lithium after it's expensive. 

Margaret: I'm gonna, I'm gonna get dunked in on, on this episode. Yeah. I disturb myself. I was like, did did you take organic account? I literally did orgo research.

So it's just on from my brain, literally. 

Preston: Well, where the energy comes from is like the difference in stability between like the pre and post donating electron, so mm-hmm. Pre donating it's super unstable, but then once you form li plus when it's just one S two, it's really fucking stable. Oh, because lithium salt.

Yeah, right. Exactly. So it's in salt form. Mm-hmm. So like lithium citrate or lithium carbonate or things like that, the bicarbonate or whatever those with it stole its electron makes it super stable. So it, it ironically, or I guess [00:13:00] unintuitive, how dangerous it is before it undergoes this reaction is that is a commentary on how stable it is afterwards.

Margaret: You love that, you love that metaphor right now for 

Preston: mm-hmm. 

Margaret: For where we're going with what we, 

Preston: I love actually, it's super stable actually. You're like, we, we love that electron property of it for batteries. So you've probably heard a lithium ion batteries. I have, yeah. So because it's, it's only got three protons, it's super small compared to all the other elements.

Mm-hmm. Like there's only two elements smaller than it. Right? Yeah. So it can pack really tightly and it's also really good at giving away electrons, like you mentioned. Mm-hmm. So that means it's great for charging and discharging. So like my electric car that I drive has lithium ion what, what brand is that?

It's a Tesla. I'm not proud of that part of it, but I'm proud of the lithium that 

Margaret: brought around, bought in December, 2024, right? Yeah. 

Preston: No, he didn't listen. Him got [00:14:00] 24. It was about six months before the got

Margaret: anyway, continue. So got lithium in there. You've got, yeah. So parts, so the grapes, batteries. But we're, we're not gonna worry about dead 

Preston: star in your car. We're not gonna worry about the batteries today. Yeah. They're stardust in my car and I'm, I'm pretty pumped about it. Now we're gonna get into how lithium affects the human body, which is the primary, uh, thing that psychiatrists care about, even though we use lithium for like a million other things.

So, um, humans have been gravitating towards any part of the earth that has lithium for a long time. But I wanna start how in Texas, actually it's like, like three hours to where I'm at, which is really funny for me to stumble upon this. So, in the mid 19th century, there were people that started making statements that their ailments had been cured when they would drink water from these wells just west of Dallas.

Hmm. And they became known as the crazy water, the crazy water wells. And this, this town of mineral wells, it's like [00:15:00] about an hour drive west of like the Dallas Fort Worth area. Um, became like a really famous attraction for this. They even had this thing called the Crazy Water Hotel, where people would go to drink the crazy to, to drink the crazy water and it would make their depression go away, or would make their psychosis go away.

They swore by it. And actually in the early night, that was me at the 

Margaret: Panera, 

Preston: you with the charge lemonade, you're like, this is my crazy waters. But it, it was like a big deal. A apparently in the early 19 hundreds of magazine named it the Nation's Greatest health resort was this Mineral Well Springs in Texas.

And when you actually look at the compounds that are in the, in those springs, they contain potassium, calcium, magnesium, and most abundantly lithium. Interestingly. 

Margaret: So they're like the, like you know, all the marketing lately that has been the like calming, magnesium citrate or magnesium glycinate. Mm-hmm.

And they're like that and lithium, it's like, 

Preston: yeah, no, it's like, it's like we got [00:16:00] potassium, calcium mag and lithium. Apparently people like taste the difference with the lithium. Like it has a distinct flavor to it. So that's how they could like tell. So I was like, I actually got really curious about this.

So I started like looking into the math being like, okay, people actually like curing their, their illnesses with this. And it was kind of interesting. So when you look at the concentrations in any of the groundwater in that area of Texas, it's about 30 micrograms per liter. And then it can be up to like 800 micrograms per liter or even 1300 in some of the most concentrated wells in the area.

So for reference, 'cause I know that probably means nothing in space. 

[music]: Yeah. 

Preston: Our one milli equivalent. Serum concentration of lithium is, um, about 6,900 micrograms per liter. Oh, so basically your therapeutic level of lithium, it's, it's about six times more concentrated than the highest concentration of these water, these wells.

Yeah. So [00:17:00] if you assume that in a highly concentrated, well, there's about 1000 micrograms per liter, about one milligram per liter. You'd have to drink two liters from the well a day to get about two milligrams of lithium per day as a dose. 

Margaret: And they were only drinking the water. They weren't like bathing in it.

No, they were just, 

Preston: they were doing everything. They were just like living in it. They came, breathing it in. Yeah. So, but I look at that on the outset. I'm like, okay, two liters a day. That could be a lot. But also you're there for weeks, you know? Yeah. Starts to build up. It's, it's well beyond a homeopathic dose, but it's not at our standard, like 300 milligrams twice a day dose that most people would start out on.

So it's almost like it's about a, it's off by about a factor of 10 of what we would give someone from the pharmacy. So, I mean, at first I was kinda like, I was a little bit dubious, but I'm like, honestly, they might be getting therapeutic levels of this stuff. 

Margaret: Well, especially when you think of the dosing we use for like the, like anti [00:18:00] suicidality mm-hmm.

Can be lower. Like, I've definitely had patients who have responded on lower that weren't really, like, maybe they were bipolar, like three, four, or like cycl imia, but they could almost reach the like a couple hundred a day. 

Preston: Yeah. Yeah. They probably could. And especially if it's in the groundwater too.

Margaret: Mm-hmm. So it's like 

Preston: anywhere they're getting water and that, that groundwater is probably also being used to process food and other things. So it's like they're probably getting trace amounts of lithium and just like about everything they're eating that's like sourced from that area. 

Margaret: Right. 

Preston: So if it's, it's coming at you from all angles, like you might be, might be getting a, a good dose of it.

So, so that's just in Texas though. I expanded my search and said, okay, what other hot springs in the world have this? And, and a ton came up. Hmm. So you might've heard of like, Glenwood Hot Springs in Colorado is a pretty famous one. Halcyon Hot Springs in Canada. There's the Iron Mountain Hot Springs also in Colorado.

Deep Creek in California. The, there's specific Lithia Hot Springs in Oregon. Uh, Arizona. And [00:19:00] then there's also some geothermal springs in Tibet, Germany, and Indonesia. 

Margaret: Podcast trip to Tibet to go 

Preston: sit in the Lithium 

Margaret: Patreon episode 

Preston: that would actually, so hype do a retreat. I wanna know what's limbs. I, I didn't find any this in my research, but I had attendings tell me that there are old stories in Indonesia and like India, where people would go to these hot springs, uh, as like spiritual retreats because it would, it would help them calm down or calm their mind.

And they, they're really highly concentrated with lithium. 

Margaret: Well, yeah, I mean like in like Catholicism alone, there's like a bunch of stories of places that like, probably not all of them had lithium in it, but like healing waters. That's like this is a pool that 

Preston: mm-hmm. 

Margaret: All of these people suddenly got better at.

You do wonder like what was in those that they, we just didn't know. Similar to the, 

Preston: yeah. And the thing 

Margaret: is that, and then also a bubble bath is a nice experience. It truly is. Estimate 

Preston: [00:20:00] combinate, combine both of them. People are good at doing stuff that makes them feel better. Mm-hmm. You know, like little 

Margaret: rats 

Preston: and cage people gravitate towards the stuff that works.

Yeah. And, and the earth is your cage and people gravitate towards these hot springs. It's for a reason. So what what's fascinating is like people would go to these springs for their mood benefits and their health benefits and other things, but the first time that we used started proposing lithium and medicine was not for our mental health.

Do you wanna guess what it was for? 

Margaret: Was it for thyroid stuff? Also, no, that's just what we found 

Preston: out. 

Margaret: No, what was it? 

Preston: Mm-hmm. It's for gout. 

Margaret: Oh, why, what was the me? I mean it does, what was the mechanism? Super 

Preston: interesting. Okay, so, um, this guy in 1847 in London, Alfred Barger, he was, he was studying, he sounds like he has like rheumatology.

Yeah. And he was looking at all these gout patients and he was like, Hmm, when I look in their blood I find these like uric acid crystals. So he was like, maybe lithium could help break [00:21:00] up the gout. Was his thought 

Margaret: like also of its, and he also prop like the chemical properties of it that 

Preston: like interact.

Exactly. They won't 

Margaret: form the crystals. 

Preston: So, um, a little bit on how lithium interacts with a gout crystal. So gout is formed by uric acid, which is sodium mono urate. Right. Or monosodium urate, sorry. Sodium is one step below lithium on the IC table. So that sodium, a monosodium urate, it can precipitate in like.

Precipitate. I mean, like, it, it forms a solid and a liquid solution, but when lithium reacts to it, it forms lithium urate, which is much more smaller. Soluble. 

Margaret: Yep. And soluble. And well, yeah. Okay. 

Preston: Mm-hmm. So lithium, um, is basically gonna shove sodium out of the way because it cares more about getting rid with electron, simplifying a lot here, but essentially it, it'll react with it displace the sodium, be like, get outta the way sodium, I'll handle it from here.

And then it starts dissolving the [00:22:00] uric acid. So like lithium will literally dissolve uric acid, which is, it's a pretty cool, um, feature of it. The other thing, so did work. Yeah, it did work. Oh, and this is a common theme we find that like lithium is effective for this stuff, but the reason that it's not used and was stopped being used is because everyone would keep getting lithium toxicity.

Margaret: Yeah. 

Preston: So we'd be like, oh, let, let blast them with lithium for their gout. Oh fuck, they're getting lithium toxicity. Oh, this is 

Margaret: worse. Actually, I'll take the gout, I'll take. 

Preston: So the, the other thing is like when they would get kidney stones or like uric uric acid kidney stones. So not only does it bind to and destroy the gout, destroy or dissolve the gout, but it also pulls a lot more water into your, um, collecting ducts or your nephrons, right?

Because it's, you can't, you don't excrete lithium once you, um, filter it out. So it, it's osmotically pulls in water into your urine so you have more dilute urine and that also helps with the treatment of stones. So it's kind bit[00:23:00] 

know. It's not a bug, it's a feature, I guess so to speak. But then with the lithium poisoning, most people would end up just having a lot of polyuria, polydipsia, dehydration, because they're just pissing out so much water because the lithium is just carrying it through. So that part helps with the stones, but being dehydrated doesn't, so we, we've been using it for gout for like 40, 50 years or so, and then it starts to get mainstream and the, um, like soda and, and supplement companies start to get wind of it in the early 19 hundreds, 

Margaret: they already had cocaine in there.

Add in a little bit of the lithium. 

Preston: Yeah, exactly. Remember at, at this time in the early 19 hundreds in the mineral springs, there's this huge craze about like health and these crazy waters, and they find out there's lithium in them. And so they're like, what if we just package this lithium and start selling it?

So like Lithia salt started hitting the shelves. So like in like the old German pharmacy, there's this, um, Lysol Bauer that they would prescribe. [00:24:00] They would also sell it in, um, sodas. So there's a Lithia Coke where they mix a Coca-Cola syrup with a Lithia Spring water. Bring that 

[music]: back. 

Preston: Yeah. And then, and then there was um, bib label lithium, or sorry, bib label Lith lemon soda, which was later named seven up.

Margaret: I knew there was a real, I love seven up growing up. Literally every time I was sick, my mom gave us seven up and I was like, healing water. 

Preston: No, but it is healing water. So seven up, I think. Seven up. If you 

Margaret: wanna sponsor this podcast. 

Preston: Seven up for treatment resistant depression. Mark. Question mark. New protocol.

Margaret: I think patient protocol. 

Preston: It had seven ingredients and one of them was lithium. And if you look at the early bottles of seven F, it would say lith ated soda on it. That was like one of the selling points. Yeah. But I would love to have 

Margaret: one of those bottles in my office. Something. 

Preston: How sick would that be?

Yeah. Wouldn't that be awesome? [00:25:00] Ated soda. I wanna get one of those like light all Bauer things too. I was, I was looking, I was looking at pictures of all this stuff. It was, it was really fun. So, but you know, you have all these like housewives that are just like pounding this stuff, trying to feel better.

Right. And we get the same problem we got with the gout patients with this. A ton of lithium poisoning. 

Margaret: What, seven up? Seven up poisoning. Mama. Slow down. 

Preston: Seven up every day is just, it's, we're getting cooked guys. 

Margaret: You greedy. You're greedy. Disgusting. So, so, so toxicity for the housewives. 

Preston: Yeah. And, and what I was reading, like a lot of it wasn't like acute lithium poisoning.

Like we think about it where you get like the GI upset and these like neurologic dysfunction. A lot of it was these like chronic diuresis effects. So people get dehydrates or passing out, getting tired. The other. Really common, um, sequelae of chronic lithium poisoning is endocrine dysfunction, which is what you mentioned with the thyroid stuff earlier.

Margaret: Yeah. 

Preston: So a little bit about that. [00:26:00] Your thyroid is dependent on iodine or iodide for its metabolism. Anytime we have a cat enzyme, someone your body lithium's like time to go ate 

Margaret: like me in the th the thyroid. 

Preston: It's like, yeah, I catch, I'll catch you in the neck later. Like it's on site. On site. 

Margaret: I'll be taking your, 

Preston: but actually like lithium directly inhibits the thyroid's ability to like take in iodine.

Mm-hmm. And then also it will bind to the places where iodine binds in thyroid globulin and cause misfolding of it. So it's harder for us to produce thyroid hormone. It actually inhibits T three, converting to T four peripherally. Mm-hmm. And you can't take in iodine, so you're just kinda like, shit. So a lot of people will develop, um, hypothyroidism mm-hmm.

With their chronic lithium toxicity. So now it's having like the opposite effect. You're drinking way too much lith seven up, you drinking hypothyroidism that you're more tired, they have cold intolerance, you have more 

Margaret: [00:27:00] seven up. Would this happen? And you're fucking 

Preston: dehydrated too because you're pissing everything out.

Margaret: What if you like people when they drink it when they were pregnant, would they, I guess would it have just the same side effect? You? This is too deep. This is too deep in the, in the, but I'm wondering if kids did that. Like if you had like a 4-year-old drinking seven up, like I'm thinking like developmentally isn't, am I thinking about the wrong thing?

Preston: The No. So, so pregnant women, if they were drinking too much of it that you can get something called Epstein's anomaly. Right. Those are the only birth defects that I'm aware of. And, and interestingly like, it doesn't actually increase the risk that much. Um, if I recall like. Epstein's anomaly. It's, it's near like, like a one in 3000.

One in 4,000 risk. Yeah. It's, it's not, and it goes to like two in 4,000. So it's 100% increase, but the absolute risk increase is not a lot. 

Margaret: What I was thinking of was, um, I don't think we call it this anymore, so I'm trying to look for the name of, if infants [00:28:00] and kids don't get iodine and they get hypothyroidism, it's the, like, they don't grow correctly.

It used to be called Cism, but it's called something else now. But I can't find the name.

I'm sorry. 

Preston: I know what you're talking about. I'm, I thought I've always been, I still saw Con Cism in my cards syndrome 

Margaret: is now. 

Preston: Oh, that's lot 

Margaret: better. I know it's a recently changed that they're like, maybe we shouldn't name it that way. Um, 

Preston: but anyway, I'm being called a little cretin by my mom. 

Margaret: Your getting canceled.

Then your mouth was gonna get canceled from this 

Preston: podcast episode. Actually, that was the only way I knew what Creon was. I thought it was just like a misbehaving kid. And then I'm like in med school and they're like, this is cre. I, mom was like, mom, what the heck?

Margaret: Like I didn't know. I didn't know. Anyway, 

Preston: okay, so moving on. 

Margaret: Sorry. But I, it's chronic [00:29:00] like iodine insufficiency syndrome is what the actual name of it is. Okay. I just looked it up. 

Preston: Good to know. Um, seven up 

Margaret: syndrome. 

Preston: So, and if you actually have the opposite of hypothyroidism, so you have thyroid storm, you can actually use lithium to treat that weirdly enough, because everything that we described, it's like inhibition of um, th globulin in the T three to T four conversion.

Mm-hmm. That's like the mechanism of methimazole or propofol uracil. Mm-hmm. Which is what we use to treat thyroid storm. 

Margaret: It's also interesting to think about the connection that is still being elucidated between like bipolar disorder and like thyroid concerns that we always check it, but even there's thought that even controlled like looks normal thyroid.

Mm-hmm. And like use of thyroid hormone in different parts of cycling and bipolar can be of use. Yeah. So it's interesting to think of like, is lithium also doing something? Is part of its action [00:30:00] also there in terms of inhibition? If there, and I don't know. Mm-hmm. 

Preston: Like is it, is it stabilizing like hyperactive thyroid function, which could be contributing to psychosis in some way?

Yeah, because. If you get thyroid storm, you can go into mania or psychosis. And, and funnily enough, the medication we use is like a derivative of ur urate. It's uracil, right? So, so even gout is still, still back in the mix. They called a lot of it like gouty mania too. They're like, this will help with your gout, but also might help with how weird you act on your gout.

You on gout. Gout mania. That was a true quote I saw in there of like several times. So, and then I just wanna touch on this. I, this is so nerdy, but these, um, endocrinologists in 2015 published using high dose lithium to treat, um, thyroid storm in a patient they tried to treat it with, with her, with methol and she had full minute hepatitis and adverse reactions to like first line treatments.

Mm-hmm. So they [00:31:00] just said, fuck it, we'll try lithium. Given this like historical thing and it worked. Wow. Which is so wild. Can you, can you imagine how hyped these nerdy endocrinologists would be in your hospital if they treated someone with thyroid stone with lithium in real time? 

Margaret: I like, I want an edit of those three.

I got Gucci. I got the same damn time came amount of high fives in the parking lot. This is out of those three endocrinologists. 

Preston: Well, well boys were about to go. No one's gone before, but theoretically Lithium could treat this thyroid storm and they're like, oh dammit, Johnson, let's do it. Her hepatitis is two full minute.

We can't use the methol. 

Margaret: Have you ever seen the movie The Fugitive? 

Preston: No. 

Margaret: Um, it's like one of my favorite scenes, like basically the movie is like the guy who's played by, I believe Harrison Ford. A cardiologist, Dr. Richard Kimball, and his wife gets murdered and he gets accused of doing [00:32:00] it and mm-hmm.

Spoilers the end of the movie is at a cardiology conference. And like the whole coverup for his wife, like the why his wife got murdered was partially because of, um, like they were lying on the research to get this big cardio drug approved. And he like comes into like a Marriott at the conference and like hits this guy with a chair and it, and it's just like that.

I want that level of cinema to depict these endocrinologists. 

Preston: I know. It's kind of like them. They're like, I'm giving him the lithium dammit. They're like mining it themselves. It's like Lokey kind of what happens. We get to it later. I love it. So, so kind of back to the store where we're in the 1940s, we have these, these lithium sodas that we've been taking for wellness, but they also also cause all these toxicity problems 'cause we're, we're really overshooting the runway and then.

Thorazine hasn't been invented yet. Right. Thine comes in the fifties and people are still in institutions that doesn't, they don't get released until 1962 with the Community Mental Health Act. So this is kind of know from the state of the psychological right now episode. Yeah, [00:33:00] exactly. Yeah. Call back. Now I want to introduce John Cade and Australian psychiatrist who was the first person to try lithium for psychiatric illness.

And he thought it was for gouty mania too. 

Margaret: Whatever. You know what, if they like it, we love it. What got us here? 

Preston: Yeah. So John Jennings of the FDA described him as the first man to eat an oyster, his prescribing O Lithium. He's, he's, we'll kind of come back to more of this interesting avant-garde story when we have this break.

Margaret: It is September and September is Sepsis Awareness Month, and it's more important than ever to talk about a podcast that we think every clinician should know about, which is the sepsis spectrum hosted by critical care educator. Nicole Kubick. 

Preston: One thing I really like about the podcast is that the goal isn't to be droning on through CME, but it really takes stories from ICU [00:34:00] teams, prevention specialists, and sepsis survivors.

It makes things conversation and easy to access. 

Margaret: You can listen to the sepsis spectrum wherever you get your podcast, or you can watch it on Sepsis Alliance's YouTube channel to learn how you can also earn free nursing CE credits just by listening. Visit sepsis podcast.org.

Preston: And we're back with the story of John Cade and the rest of the, the Australian psychiatrists from down under 

Margaret: you do the accent for the next five minutes telling this. 

Preston: So John, John was good old con from Melbourne, and he was thinking that these patients was, was going manic because they, they gout. He said, I'll, sorry I didn't stop.

But basically he, he thought that similar to doctors before him, that gout was causing these manic episodes. Mm-hmm. So he was [00:35:00] actually trying to target gout in their brain by giving them trials of lithium. So he, he put 10 patients on lithium citrate and 10 on lithium carbonate. And much to everyone's surprise, there was a huge improvement.

Some of these patients that, um, yeah. And some of the patients. That had been like manic psychotic for years. And in this, these custodial cares became so normal that they could return to society. 

Margaret: Wow. 

Preston: And they were like, people were like amazed by this. And this is in 1949. So this, he like publishes this, this humble paper in Australia.

And then at the same time, this is, is like the worst timing. They did another study on congestive heart failure with lithium, where the researchers were like, what if we replace sodium chloride with lithium chloride? You cannot make this stuff up for heart failure treatment. [00:36:00] Okay. I don't know what they were thinking as to why it would work.

I didn't read too much into the paper, but basically they all got work. Lithium toxicity did not. Yeah, it did not work. So God damnit guys. So, and then it was really bad in this paper. Um, two of the patients died from lithium toxicity. Because they have congestive heart failure. So like on top of all this stuff, they're not moving fluid through their body.

So lithium's is gonna accumulate like crazy, right? So then right around the time that John Cade publishes this paper about it being helpful for mania, it's getting all this bad press in the states and everywhere else. 'cause people are like, you know, lithium bad has killed all these patients. So now his kind of, his paper falls to the wayside and kind of, it's like an echo that no one really picks up on till a couple years later when another, um, Melbourne psychiatrist got curious about us, we were still in Australia and they tried again with a hundred patients said of the original 20.[00:37:00] 

And they found it to be particularly effective for the treatment of mania. Though they were like not having any like robust trials yet. They're just seeing that like, people are getting better. They were manic psychotic. Mm-hmm. Now all of a sudden they seem to be like functioning normally again in, in a way that we've not seen before.

'cause we have like, Thorazine doesn't come out for another five years. We, we don't even have any drugs. We don't have any working. We just have 

Margaret: the malaria seizures that we're inducing and that's it. 

Preston: Yeah. And, and, and lobotomies I guess. And the lobotomies. Yeah. That's, that's, and that's the competition right now.

Margaret: And the purposely crashing blood sugars, comas, we have those options. 

Preston: Yeah. And then, yeah, and then in, in other specialties, the Tuskegee trials are still going on, so interesting time for science. Um, so, but moving forward, the, the Danish actually were the first to try a real trial with it. So they were paying attention to the, what the Australians were doing.

[00:38:00] This guy Morgan Chao, made the first controlled trial for lithium where they actually like flipped the coin to randomized patients. Hmm. And there were, um, I'm seeing 18 total manic patients, but I think I saw earlier there, there was, um, about 35 in the study. Uh, anyways. They, he did shifts with medications in this one.

So he started people on placebo and then switched them to lithium and then started them on lithium and switched them to placebo. And then he also thought that it was the carbonate that might be doing something. So they gave, they gave one group just carbonate because of the lithium carbonate? Yeah. Yeah.

Right. And what they found was that there was a huge difference in two groups. The group that was switched from placebo to mania, they saw like 40 more observations of decreased mania, and in the group that was switched from lithium to placebo, they saw people having more mania. So we had a bidirectional relationship.

Now you switch some to lithium, their mania goes away. You switch someone off, lithium, their mania comes back. That was a really [00:39:00] powerful study at the time, because now it's more than just, oh, we're giving someone this drug and we're seeing that they like actually get better. It's not like getting better concomitantly.

It's like mm-hmm. We're seeing the effect on both sides. So momentum begins, people are starting to prescribe it a little bit more. In Europe, we run into the same problem. Round three, everyone gets lilium toxicity, you're like, 

Margaret: too much. Fuck. 

Preston: So, um, what was great actually is in, uh, 1958, they came up with a new ome that was able to accurately detect, um, like chronometry where you use, like, I, I don't know much about.

Okay. That's okay. I 

Margaret: was just, I've never heard that word. Basically it's a 

Preston: lab instrument that you use to detect metals in solutions. Okay. And so it helped them give more accurate readings of lithium. That's all you need to know, so, so. We started getting, I'm 

Margaret: sorry, I'm Turing you being like someone coming into your like, private practice someday and it's like you [00:40:00] have like a real microscope and like ome and like just hanging out in your psychiatry office.

I'm sorry. Continue. Yeah. 

Preston: We're, we're a one stop shop here. This is this beating the, don't worry. Just didn't go 

Margaret: to med school allegations every day. 

Preston: So, um, this is, we're now in to like the late fifties, um, early sixties and in 1960 was the first time the US did anything with Lithium and of all places. It was Michigan.

Margaret: Michigan, 

Preston: university of Michigan. Yeah. So this guy Han, he uh, was reading all of the, the trials and successful Lithium and with some help from the National Institute of Mental Health, he, he got funding from them. He was like, I'm gonna try treating these patients. With lithium, but they, well, we don't have any, like lithium being prescribed into pharmacies.

It's, it's not like medicinal grade in any way here in the us Not really elsewhere either. [00:41:00] I guess he could go find seven up, but instead he goes to these chemical supplies stores and just buys lithium.

Margaret: I feel like we're gonna get o lithium toxicity again. And, 

Preston: and then he goes to the pharmacy and is like, can you put this in a capsule? And they're like, okay.

So literally just like, okay. And then I, and then I go to the hardware store and then I carry my fucking of lithium back over to the pharmacy and they break it up and put it into the capsules. And then, then they were giving to patients. But, but it was working like, like they were seeing like pretty effective responses.

And, um, Gershon, he, he, he later moves to St. Louis and then to New York Medical College. Yeah. Where he became, uh, one of the prominent researchers in, in Lithium after that. And then a year later in 19 61, 62, wash U starts running a similar operation. 

Margaret: Gang. Gang. 

Preston: Yeah. [00:42:00] Yeah. 

Margaret: Gang, gang. 

Preston: So, uh, at, did you ever, did you rotate at Barnes Hospital?

Margaret: Girl? Did I rotate at Barnes Hospital? Yes. There's a comment in one of our Instagram posts for, shout out our podcast as an Instagram where one of my prior, like the resident I had when I was a med student, it was the video where we were talking about like crying or something in the hospital. And she, she commented like, glad to know other people also cry in Barnes Jewish.

And I go, I know those, the best spots for crying. So yes, I have, 

Preston: okay, you cry. Damn, you cried in Barnes Hospital. Well, maybe I could have used 

Margaret: Lithium during that. 

Preston: Probably could have. So they, they were doing kind of a similar thing where they were just like buying this lithium, I don't know if they're going to the chemical supply store, but they were having the pharmacy on site, basically packaged them into capsules.

Mm-hmm. And they had this patient. Who had failed Thorazine in 18 trials of ECT because Thine been on the market for like five years or so now, but he got better with Lithium and everyone in Barnes was like hot dog. So, so after like that kind [00:43:00] of, um, crazy case report, um, lithium became like one of the mainstays of mm-hmm.

Treatment at Barnes, and they were kind of one of the leaders in the area for a while, um, in adopting Lithium. And, and it's kind of important to note that because there's almost like a gap between Europe and the US as far as their attitudes go towards lithium. The US in general is kind of like the last to adopt lithium, and they're kind of the most suspicious consistently, which, which has been kind, kind of strange for me.

Hmm. So over the, over the next decade or so, now, this is the sixties, they run four more randomized controlled trials in, um, like Sussex, the N-I-N-I-M-H does one, um, New York Hospital of Cornell does one. Mm-hmm. They overall report a response rate of about 78% for mania with lithium, which is wild. Like we don't, we don't see numbers like that in psychiatry.

No. For response rate. Like ever. 

Margaret: Not now. Not even now. [00:44:00] 

Preston: Yeah. This is like being taken up by all the psychiatry, um, uh, hospitals are across Europe, so France, Germany, Italy, uk they all start manufacturing medical grade lithium salts. The only difference is some people are like, oh, we'll try lithium citrate, we'll try lithium carbonate, you know, try, um, you know, dye, lithium something, and the US is like, no.

Yeah, the FDA like refuses to approve it. 

Margaret: So, but like entirely, 

Preston: it just, just, so this time in the sixties, they hadn't, okay. They hadn caught on yet every one 

Margaret: lithium. So it was like, no girl. 

Preston: Mm-hmm. So they were kind of thinking, they were, they were accepting of these like. Investigational new drug applications for some people to try to like, get permission to use lithium.

But a lot of people ended up just kind of doing what they did in Michigan and at Wash U and this like underground lithium [00:45:00] culture starting in psychiatry where people would just kind of be like, I know Lithium works, so I'm just gonna fucking use it. 

Margaret: Yeah. 

Preston: And, and actually we kind of bullied the FDA into approving it.

So in 1969, um, I, I didn't write down his name, but a psychiatrist came out on TV and basically said, I'm gonna use lithium, whether or not the FDA approves it because it's just like bad. Good. And, and then in 1970, the US finally becomes the 50th country to approve the use of lithium for bipolar disorder.

Huh. Which is not, you know, we're a little bit behind 

Margaret: Yeah. 

Preston: On that one. 

Margaret: That's interesting. I like, was it, was it just thought maybe though like. We were so scared by that one study or that was it the like anti sort of anti Europe. Europe doesn't know what we're doing. American centralizing, that's like we can't trust their science.

Or 

Preston: maybe I, I, and I'm really not sure actually. So I, I guess I, I was perusing through [00:46:00] most of this and the kind of seeing, and we can, I can only guess it's like the differences right now, but I think there's kind of a lot of differences in the way that like Europe and the US practice psychiatry and even outside of like lithium and some of these other like, medicines that we use, like, like aga Melaine I think we've mentioned earlier is like a melatonin, um, agonist and an SSRI combined, right.

But similarly, like there was like some toxicity that we saw in one of our trials and we just pulled it from our markets. But Europe uses it like pretty much without, um, consequence. 

Margaret: Mm-hmm. 

Preston: So yeah. I think we, we could do another episode on like where we do a deep dive on like differences in like the culture groups between, there's someone 

Margaret: actually from Australia.

Preston: Yeah. Actually that'd be really, that'd be really interesting. And I think a lot of the culture and how you prescribe medicines or how you do surgery, it's, it's almost like apprenticeship. It's like passed down. Yes. So the person before you wasn't excited about lithium, so [00:47:00] you're not gonna be excited about lithium, so you're gonna teach your med students to not be excited about lithium and Right.

It just kind of continues like that. I think there might be like an aspect of that in, in both of these Sure. Different cultures. So, um, kind of after it was approved in, in 1970, we started having some of these lithium clinics pop up. Mm-hmm. And there's one in set up in the West Park in Epsom that started following all of their patients, um, that they were prescribing lithium for.

And their, um, main outcome they were interested in was suicide. So they found that, um. The, the standard rate of, or the median rate of suicide for the patients that were coming through their clinic was about seven in a thousand. Mm-hmm. But in this group that was treated with lithium, it dropped down to one per thousand.

Oh. So they, they were seeing significant decreases in suicidality across the board. And it's interesting because now in the seventies they started looking at lithium for its [00:48:00] prophylactic benefits. Yeah. 'cause before everyone's worried about treating mania, but we had other ways of treating mania. ECT was really effective for treating mania.

And we'd also just basically blast people with barbiturates until their mania would go away. And both of those were kind of effective. But what we really sucked at was keeping the mania from coming back. Yeah. And that's where lithium made its money. That's where it was. It's worth its weight gold or it lithium, I.

Um, a, a meta-analysis, kind of like looking at all these now, prophylactic measures in the nineties found that the relapse rate for depression was 74% for patients on placebo or didn't receive any treatment uhhuh, and it it dropped to 29% on lithium. Wow. So it's almost a 60% reduction in relapse of depression.

So not only does it prevent me from coming back, but also prevents depression, like it's, 

Margaret: yeah. 

Preston: In every sense of the word, a true mood stabilizer. 

Margaret: And was that in non patients who'd never had mania before? 

Preston: Um, or just 

Margaret: in bipolar? 

Preston: That was in, [00:49:00] um, I guess described as manic depressive patients back 

Margaret: then. Okay.

Preston: Mm-hmm. So it was in bipolar depression. And then, um, so a lot of this information has come from, from an article on the, the history of mania. And I actually wanna read, um. An excerpt from it right here, which I, I found poignant. In retrospect, the miracle of lithium was not in its treatment of acute mania.

As Dennis Char at Yale University put in a 1995 meeting in the Psychopharmacologic Drug Advisory Committee, neuroleptics or even high-dose benzodiazepines are quite effective as treat of acute mania. The issue was always prevention of relapse. The paper continues with the exception of ECT. Lithium is the single most effective treatment in psychiatry.

Its side effects are easily managed and many patients stay on low dose lithium for decades. Its benefits in terms of relief of mania and prophylaxis of depression are incalculable. So it, it's a really powerful medication. But I've also found, and this now I'm talking like from personal anecdote, a lot of [00:50:00] people are hesitant to prescribe lithium.

Yeah. And I've, I found that when someone comes in and they're, they're acutely manic most of the time. Either like my colleagues or my, um, like supervisors will recommend starting with Depakote. 

Margaret: Hmm. That's interesting. And because like my, and that also could 

Preston: be like an institution. Institution's been like, 

Margaret: no, my institution's like lithium.

Preston: Yeah. And, and I have some attendings that are very like lithium forward I guess. But there is some interesting commentary on that I read in the paper too, where some people were really trying to vilify and like play up the side effects and toxicity parts of it, while also pushing the use of Depakote or other like anti-epileptic medications as mood stabilizers.

So kind of the, the paper and the history of mania con concludes actually by saying, by talking about these almost like political campaigns that people have had mm-hmm. About trying to use Depakote [00:51:00] instead of lithium for the treatment of mania. Even though every way that we can measure, um, the two drugs competing side by side for lithium, both the treatment of acute mania and prophylaxis, lithium outperforms Depakote.

Margaret: Yeah. Yeah. That's interesting because I, again, anecdotally, my experience has been more lithium forward. Like we very rarely an outpatient prescribe lithium, I mean, prescribed Depakote. We very rarely prescribe Depakote. We would, we kind of only use Depakote once like, and an inpatient even. It's like we would use it in patients where like other things weren't working and there was like persistent, aggressive and violent behaviors.

But like my institution's pretty avoid not, you know, avoidant of, uh. Depakote side effects. Yeah. 

Preston: Yeah. Personally, I don't, I don't like Depakote that much. I think it, it kind of stupors people. It makes you dopey, it causes weight gain, like worse than lithium [00:52:00] would. I, I don't know. I'm, I, I, that's the reason why I'm doing this whole episode.

I love lithium. I think it's a good drug. 

Margaret: I think the thing that comes up comes up when we can't do lithium, or like, one of the things that comes up is the use of it in an illness where being able to like go get troughs and like, get lab levels and keep someone in the persnickety window of lithium.

Mm-hmm. Depending on how sick someone is. I think that part can be a limiting factor in how good it is as an agent. Because it is quite an active process compared to like anti-psychotics, even compared to Depakote. 

Preston: Yeah, absolutely. And like in, I think personally for me, like where I, I'll also. Choose Depacote or Lamictal or something over lithium as if someone has kidney problems.

Mm-hmm. Or they, they have, like actually in San Antonio, if you're unhoused because it get so hot out, people get like dehydrated. Yes. Like the on lithium wouldn't be like, helpful for them. They, they could [00:53:00] actually get in serious trouble. Um, but yeah, it's like you said, if they're so medically sick that they, we can't keep them safely at normal.

No. I mean if 

Margaret: they're, I mean if they're psychiatrically sick. 

Preston: Oh, okay. Yeah. I think, and I think, I mean it's all types of sick. 

Margaret: I, um, this may be, I wonder how you'll feel a year from now and you've done more outpatient. Because the, to me, the thing is like if you have someone who knows, shows 50% of their outpatient appointments, after that happens a few times, it becomes way less clear whether.

Lithium would be the right agent for them. Not as like a punitive thing, but because it's like if we're ne how comfortable are you prescribing if someone may never get labs and will not show for eight months at a time? 

Preston: Yeah, 

Margaret: and I it, I don't necessarily go towards Depakote then it's usually more like second gen or like Lamotrigine or something.

But like, yeah, sure. I feel like lithium in the hospital setting versus lithium in [00:54:00] outpatient is kind of a different ball game. 

Preston: Yeah, totally. 

Margaret: Okay. Would agree. It's still great. It's still like, like a, I want people to be on lithium rather than Depakote, but it's like, will this stuff actually happen for 

Preston: mm-hmm.

Keeping lithium safe, what do they say in peds? The best medicine is the one the patient can take. Yeah. So as we kind of wrap up the history part of it, I wanna segue us into a little about the mechanism of lithium. And this part will be short because to be honest, we don't understand a lot about how it works.

And I think part of this comes from, we also don't understand a ton about how mania works either. So we, we have like a clearer pathway in something like schizophrenia or psychosis, where we understand that like increased disinhibited dopamine and some of these pathways can cause psychosis, mania and depression happen across a lot of functional and anatomical networks and structures in the brain that are really hard to [00:55:00] pin down.

But we do know that lithium does a couple things. So we know it releases brain derived neurotropic factor, which can help with preserving and actually sometimes increasing brain volume in the amygdala, prefrontal cortex and hippocampus. Um, these are all regions that regulate memory and emotion. It also decreases the release of glutamate and dopamine, which are related to psychosis and also excited toxicity.

It increases the release of gaba, it reduces oxidative stress, and it lowers apoptotic processes or the destruction of cells. As far as like how this helps with mania, how s psychosis, there's not a clear link, but we know that it's probably interrelated to all of these functions. So, in summary, long, long ago, we had a couple black holes in supernovas, a couple stars dancing around each other that, um, combined to make these weird lithium salts circled and formed our planets.

They deposited in our [00:56:00] hot springs that we've been going to for centuries to help with our mood. And we figured out that we can take it out, it up to distill and assault and actually use it to treat our mental illness. There's all these wonderful magical things. So every time that you're prescribing lithium, just remember you're prescribing stardust that was formed in a black hole, which is pretty fun 

Margaret: and loves the thyroid.

Um, yeah. Do we wanna talk all about prescribing it? 

Preston: Yeah, we can that, that, that actually kind of comes the end of everything I had to talk about. So if you wanna move on to prescribing it. 

Margaret: Oh, okay. Um, we'll just talk about a little bit if you guys wanna hear more about like, formulations and prescribing it.

I don't think there's a ton of it. I mean, I guess the first question is what actually is lithium toxicity? Like, what do you look for if someone comes back to you mm-hmm. And says, Hey doc, the lithium's been working great. Um, I had some knee pain for a couple months, so I started taking ibuprofen and the knee pain feels better.

But then suddenly I started shitting with this is like, just like actually what happens. Yeah. [00:57:00] So what do you look for And lithium toxicity. 

Preston: So initially, like you mentioned, you look for GI upset. 

Margaret: Mm-hmm. 

Preston: You can look and then, like we already mentioned, signs of like dehydration, so like fatigue, um, cold intolerance, uh, and then numbness and tingling can happen too.

Mm-hmm. So basically GI symptoms. Mild neurologic symptoms and then, um, total volume status disruption. 

Margaret: Yeah, and I think one of the things you mentioned in some of the history is there's also like a difference between someone suddenly having a lot more like lithium in their body and that being like acute toxicity versus like mm-hmm.

Chronic effects on the body from being in lithium. Um, and so I think one of the things to think about is the chronic impact in terms of thyroid can be a big deal mm-hmm. For a lot of people, right? Because they can end up needing supplementation. Um, the GI stuff long term is not as much as [00:58:00] saying it's the short term kind of acute change in dose that we worry about.

Um, but then the long term chronic impacts can be from like a CNS perspective, like a tremor. Like ataxia, as you mentioned, short term, but also can be long term. Mm-hmm. Um, there can be more rare things than like, what I won't mention right now, but then the big thing is chronic kidney issues from lithium long-term, which can happen even without, you know, being in the toxicity ne necessarily.

Right. So I think that's like the concern also for lithium for people is it's worth it and you can monitor things and you can treat these other parts, but, um, renal function can be a big kind of limiting thing, especially depending on like how healthy are their kidneys from other stuff. As we move into like geriatrics, like 

Preston: mm-hmm.

How 

Margaret: is their renal function, how is their vascular and metabolic function impacting renal clearance? [00:59:00] Um, the interesting thing with that is like, people who are on dialysis, it's actually much easier to do dosing of lithium by working with like the renal team, but. People who are like somewhere in the chronic kidney disease spectrum, it is harder, um, to, to figure out, because it's like once you reach the point of dialysis, like you can, like you can work with them to kind of, everything's 

Preston: regular, 

Margaret: right?

Like you can figure it out. But when you're in the spectrum of like failing kidneys, how do you dose it? How quickly are those things changing? Can be a great time to talk to nephrology, uh, and work together as a team. Um, other things, I guess I would say, just in terms of prescribing, you mentioned that we start, I feel like I usually start outpatient with like when they're, when someone's not like necessarily acutely manic or danger, starting with like 300 or 600 at night and then going to BID dosing.

So twice a day dosing. Usually ending up somewhere between like 900 and 1200 milligrams total per [01:00:00] day and eventually trying to get all of the dose at night because it's. Renal protective if people take it at night while you're sleeping. So technically some worked at night, I don't think this would be true, but before you sleep, there's like a change in how much it's hitting, uh, like the kidneys and like being filtered in different way by some being lying down versus like being up and around, which is odd.

Mm-hmm. But is a thing. So you eventually, if you can, for some people, if it's tolerable to take the dose just at night, um, and they sleep at night, so they're not a healthcare nighttime worker, it is important for the renal protective part of it. Um, I think that's. The other thing that, again, always talk to people about is anything that can impact their kidney function or then their volume status.

So you mentioned a little bit about like, um, like heart failure, but a big time we think about it is in pregnancy, so it's contraindicated in the first trimester or when people are trying to conceive. But after that, people can talk with their psychiatrist and [01:01:00] consider going back on it once the heart has formed in terms of the Epstein anomaly.

And so lithium, but also in terms of dosing, some people stay on it even throughout because the risk of a manic episode or a significant depressive episode during pregnancy is more dangerous than the one in whatever thousand risk of Epstein is. Um, the volume status changes, and so the lithium dose has to change in accordance with the mother's volume status.

Yeah. And then also you ask them about dehydration, like you're saying. So changes in heat, but also any pain where they start taking. You'll be surprised how many people are just like knocking back ibuprofen every day. Every single day. 

Preston: And if you're a med student listening, that's like a very classic either shell or board question that you'll get where some patient will come in, they'll kind of try to mask it.

They'll be like, he had a manic episode and they started him on a medication. And they'll be kind of like cagey about it in [01:02:00] the question stem. But then they'll start taking ibuprofen or they'll get like a UTI or something or an A KI and then immediately start shitting their pants. 

Margaret: Yeah. Attacks. They're like, what's going on?

And then the range that we look at. So just in terms of very basics, although again, if people want this episode, we can go more into this. After you start lithium, five days after you start it, like you get a trough level, usually once they're more in the like above 600 total daily dose range, and you have them take it 12 hours after taking it, if they're.

12 hours after taking it at night before they would take the morning dose at their BID and you want 'em to be generally within the like 0.8 to 1.2 range. But, um, some people will have an effect at like lower than that and some people will need to be higher on the scale. Yeah. 

Preston: Interestingly, um, all the kind of studies that I was talking about in the [01:03:00] fifties and sixties, they were shooting for about 0.8 for all those patients.

Mm-hmm. So they were, they were on like the lower end of what we consider the therapeutic range now. 

Margaret: Yeah. Yeah. Um, I'm trying to think of anything else. 

Preston: Yeah. And with a lot of things it's, it's like you treat for effect, I guess when you're treating mania more so, but with prophylaxis, I think you'd still wanna get to the, the therapeutic window.

Margaret: Yeah. 

Preston: Because I'll say, 

Margaret: what's your experience been with like actually using lithium acutely for mania? Because I feel like we usually now use like. You like in the emergency and inpatient setting, we use the atypical or we use antipsychotics and then start them on lithium. Mm-hmm. And monitor. 

Preston: Um, if somebody is acutely manic and agitated, we often will do antipsychotics.

So, we'll, we'll, I'll usually do like Olanzapine 10 or something with an I am backup. And then, we'll actually, we'll schedule benzos [01:04:00] sometimes, like what they do, like what they were talking about. And then I'll, I'll usually start them on lithium either a day or the next day. Yeah. 

Margaret: Yeah. Because I don't use it.

'cause you know how there's like, there's like some chart from like boards prep that's like acute mania versus, you know, like long ongoing on and off, or like, is it hypomania? What is it? Mm-hmm. And having very different choices. But I feel like in the ed, I, I think also, like if someone's in the emergency department with mania, it's usually pretty significant.

Like disruptive mania to them and they've gotten brought in by someone else. 

Preston: So like I've had some patients that like they do end up in the emergency department and they're like, they're really hyperactive, but they're pleasant, you know? Yeah. And then it was really just be they became at the behest of a family member and they're agreeable and it's just because they've noticed it's like change in their status.

Those might not be patients that will like, start with atypical antipsychotics. You may just offer them lithium mm-hmm. From the beginning. Mm-hmm. And they, they'll be okay with it. But the patients that are getting [01:05:00] agitated and like having these like behavioral codes, will, will lean more on the atypicals.

Margaret: Yes. Um, as with many of our meds, lithium can also impact the heart, uh, can long-term cause myocarditis and then also though can needs an EKG if they're gonna be on it. Um, or QTC stuff and just other arrhythmias, which I don't know how much of that is similar to other. QT prolonging, like in the antipsychotics as much as it may be related as well to these changes in renal function and therefore like electrolyte balance.

Mm-hmm. So that's, that's clinical lithium in a nutshell. In a nutshell. That's me vomiting that at you guys. Sorry, but I figured you might wanna 

Preston: Thank you for tying that up in a bow at the end. I think this will be really helpful for anyone who's like clinical, who's like, I was hoping to get a lithium tip at some point through this, and I'm just like, no, we're talking about the drama.

So you're like, you have this, 

Margaret: hey, now they have a, they have. Part [01:06:00] one of as much as they could one about lithium. Mm-hmm. But, 

Preston: but this was fun for me. I think I, I kind of wanna do other elements now. I wish we, I wish we used more. Maybe I should be asshole episode. Use more elements to treat psych illness.

Margaret: Just go outside and be like, what do we got going on? What can I 

Preston: just throw a dart at the periodic table? I was like, oh. Like when I was reading about like, the cathodes and anodes and lithium, I was like, I miss chemistry. I was a chem major. I'm like, this was fun. I liked learning about this. 

Margaret: We are falling into our, uh, archetypes again.

Preston: Yeah. 

Margaret: We, like, I was a chem major and I was like, I was theology. Well, it, it's a perfect place for us to meet the brain. What the brains choose. Mm-hmm. Yep. Good job. Yeah. I know more about this. I'm, I'll try out your stardust line. See, in the emergency department, 

Preston: I, I actually use that with people where I'll, I'll say like, you know.

People used to go to Lithium Springs back in the day, help 'em with their mood. It's, it's a technically a natural compound. [01:07:00] Like anything else, like, oh yeah, I guess, you know, you gotta, you gotta appeal to the inner granola in all of us. 

Margaret: It's totally natural. 

Preston: It, it's, you can't create or destroy it. 

Margaret: I feel like mania is like one of the things that, like, you, like one of the things in psychiatry training in particular where you're in the emergency department enough that you do eventually see real mania and the first time you see it, I feel like sometimes you're immediately, you know, it's mania, but sometimes it's like, as an intern, I feel like that I would, I saw it for the first time and I was like, what's going on?

Like, are they intoxicated? Like, what's happening? Mm-hmm. And had done a lot of psych rotations and they were like, that is the truest case of mania I've ever seen. I was like, oh. So, mm-hmm. We take for granted, I think, you know, having Thorazine and having lithium in modern psychiatry, but yeah, there was only sedation before.

Preston: [01:08:00] Yeah. And, and there was a time where probably a lot more manic people were running around. Yeah. 

Margaret: I mean, I think the therapy side of bipolar is super interesting. Like in terms of when you're managing someone, like how do you make sense of if you feel happy that that's almost a dangerous trigger for you.

Like that it's like, am I about to be manic there? We could have the whole discussion on bipolar and people who are creative and the history of the artists there that like the bipolar mania feels like and may actually be the time they're more creative, even though it's like not sustainable. 

Preston: Yeah. It's like they, they put themselves into overdrive and then cut an album and it's crazy.

Margaret: It's 

Preston: graduation. It's really good. 

Margaret: Allegedly. And like, you can't, I mean, I think that it, it's like a true grief, like to have mm-hmm. Like in that, like, I don't think there's, like, I think sometimes people will go to psychiatrists and they'll be like, [01:09:00] well, you just need to not, it's like, I get the, like, question for your life.

Like, if you're someone who feels like the only good times, like you feel like you're in depression or you're that, like, it's hard to be judgmental. 

Preston: Mm-hmm. 

Margaret: When someone's in this illness and you haven't been in this illness and like 

Preston: Yeah. Would you, 

Margaret: what would you choose? Like, I don't know. I can't, I honestly do not know what I would choose if I had to make that choice for my own self.

Preston: I mean, I, I feel weird saying this as a psychiatrist, but like from the outside looking in, being manic seems awesome. Like you feel on top of the world, like you can accomplish and like who wouldn't wanna feel that way, you know? 

Margaret: Yeah. Well, especially if you're in between periods of depression. 

Preston: Yeah. And like it's destructive to you and you recognize that like ultimately it's a negative on your life or has this negative impact on your life.

But it's a great feeling in the moment like, so I just, I think we 

Margaret: need to do another bipolar episode where we talk about like diagnosis and like also like yeah. Is the thyroid involved? Like mixed states? What are those? [01:10:00] Is there such a thing as bipolar three and bipolar four? Why do some people take an SSRI and it makes them become hypomanic.

Yeah. We got a lot to say about bipolar structure. You're 

Preston: right. We really kind of started at lithium and then came in, was like we started with stars, started touch on bipolar. Yeah. But next time we can start with bipolar and I would have a lot of fun going into the history of bipolar too. I think there's a lot of fun characters.

Time have bipolar and I have lot into the 

Margaret: modern clinical practice. Preston's like what if we did a story of like, okay, I'm not gonna forgive you guys information on prescribing it, you primary care doctors, but. Let me have fun. I'm letting you have fun. I do let you have fun. I like learning from your story.

I'm gonna dunk on this episode. 

Preston: Well, all that being said, if you're a listener here, thank you so much for listening. Thank you for bringing us along for your, your car rides and your dog walks, and if you're in a coffee shop right now. Close your laptop for your, for your gout attacks. Yeah. [01:11:00] Let us know how the show is.

If you like these Preston led episodes where we talk about, um, a single mo, single Adam, and I'm not implying that you don't like them. I'm just, just asking them 

Margaret: just like, I mean nice to me and not a Zoom. 

Preston: Come chat with us. And our fun Human Content podcast family on Instagram and TikTok at Human Content Pods, or at our How to Be Patient Instagram page.

We have 2,399 Instagram followers now, so you have the rare opportunity to, to be the 2400th 

Margaret: early investor. You can visit grounds, you can get on our wait list for visiting those wells with in them.

Preston: You can always see more from me and Margaret. On our respective Instagram pages, so I'm at it's prerow Margaret at Badar every day. You can also find full versions of this podcast on my YouTube at it's prerow, and then you can find us audio or video on Spotify and then also on Apple and anywhere else you get your [01:12:00] podcasts most likely.

Guess okay. I always say everywhere you get to podcast, but I don't know where people get podcasts. Like they might get 'em from weird places, but. Thanks again for listening. We're your host, Preston Roche and Margaret Duncan. Our executive producers are Preston Roche, Margaret Duncan, Wolf Flannery, Kristin Flannery, Aaron Corny, Rob Goldman, and Shahnti Brooke.

Our editor and engineer is Jason Bizzo. Our music is Bio Benz V, so learn more about our program, disclaimer and ethics, policy submission, verifications and licensing terms, and our HIPAA release terms. Go to How to be patient pod.com. Reach out to us at how to be patient@humancontent.com with any questions or concerns.

How to be patient is a human content production.

Thank you for watching. If you wanna see more of [01:13:00] us or if you wanna see, this is lilac. She's my cat. She's gonna be waving her hand at one of the floating boxes, which will lead to more episodes. Lilac Point to the other episodes. Lilac doesn't know what the internet is, but I swear they're there. They, they probably exist for real.

But in the meantime, I'm just gonna pet lilac and then I'm gonna go dance in the background.