Welcome to Stuff You Should Know, a production of iHeartRadio.
Hey, and welcome to the podcast. I'm Josh, and there's Chuck and Jerry's here too. Well. Actually, that's not true, isn't it. It's a dirty, dirty lie.
You're talking about.
It's just me and Chuck. We're producing our own jam today. I guess you could say, and this is stuff you should know.
That's right, and the listener will never hear where we edit out when Jerry burst into the room in two minutes. We'll just cut that out nice and clean.
We should just leave it in once, just a really kind shure.
Yeah, guys.
Uh, she's got like a little bit of miso in the corner of her mouth.
Oh, always a little crusty miso.
So Chuck. Today, we are doing something in grand Stuff you should Know Fashion. We're doing a tangential episode where we haven't done like the core episode that it relates to.
Have We never done one on depression.
Actually, I could not believe. I looked on the stat sheet maintained by Jill Hurley, which is infallible. I looked all over the internet. I sat there and had a conversation with myself. Nothing. It's not there.
Yeah. I mean that's so like us to hit stuff like bipolar first.
Yeah. Yeah, we did do bipolar, we've done PTSD, we've done ADHD obviously all that, but we'll definitely do depression at some point.
Okay, I think it makes sense maybe to cover this first. So how about that?
Sure? Think it to me?
Yeah, put that in your paulm and wash it down with some water. How's that for a segue?
Oh that was a good one. That was great man. So yeah, we're talking about antidepressants. That was a great one.
Thanks.
And to talk about antidepressants, we really do have to kind of give at least the briefest overview of what depression is.
Like.
It's kind of everywhere. I saw something like sixty million adults in America and I think they define that over age eighteen these days for this kind of stuff have some sort of diagnosed depression. I think twenty million of those have major depressive disorder, which also is called clinical depression or unipolar depression, as opposed to say, like bipolar where you have ups and downs, mania and depression unipolars
like just depression. And it apparently is picking up so much that the World Health Organization is saying like, hey, guys, by twenty thirty, that will be the leading disease essentially in the entire world. Depression will be just the way that things are going and everyone in the world. I was like, yeah, you know, and it just kind of is going from there.
Yeah, I mean, that's a good overview, you know, without getting into the weeds as far as numbers go. Symptoms as you might imagine are they're sad, disrupted sleep, feeling like you're worthless. Sometimes it affects your concentration. Sometimes it affects your ability to even experience pleasure at all. Even you know, when you're you know, doing something that might ordinarily be fun for you, it's not fun. It's not being sad in a moment or being blue for a
little while. It is a persistent thing where it disrupts your life. It interferes with your life. It can interfere with your relationships and interfere with your relationship with yourself in a big, big way.
Yeah, and for a lot of people, I think for most people, statistically speaking, it's chronic or recurring. You don't just have one episode. It can keep coming back and back, and it's nothing new like depression is not new, although it does it has really kind of picked up as far as diagnoses and prescriptions go. But I mean, we used to call it melancholy and they associated it with black bile all the way back to Hippocrates. And depending on what culture you were from, they would either say
tell you that you needed positive rewards. It's say you lived in Persia in the ninth century, or if you were in medieval Europe, they might burn you at the stake or something like that. Luckily, we've come a long way with treating depression. That's the that's I think we should say here at the outset. That's the message we're trying to say, like it is highly treatable. Like if you have depression and you're you're not treating it, there's
definitely hope, So please don't feel like there's not. There's plenty any of hope that if anything, hopefully. That's what we get across this in this episode. But there used to be they used to give people edemas, they used to give people baths, positive thinking, diet, exercise, And what's interesting, Chuck is some of those are still prescribed today. Depending on the severity of your.
Depression, yeah, for sure, and those things very much help. And I'm glad you said that what you said just a second ago, because when I said, I sounded very very down when I said that the symptoms are and I pause and just said sad. There is a lot of hope. But you know, I have everybody you know has if they don't suffer from the depression. You have people in your life and your family and your friends that do it. And it makes me very sad because these are, you know, great people who have a hill
they need to consistently hike up. And I imagine it is something that drains your life force. And we're here to talk talk about some of the ways that you can change that.
Yeah, just as an aside, every time I think of depression being like really accurately portrayed, I think of Kirsten Dunst in Melancholia, the large von Trier movie. Yeah, Lars von Trier, of all people, seems to have most accurately portrayed clinical depression in that movie. It is a great movie, but she just does an amazing job. Like there's a part where she's just in physical pain, such physical pain from being so depressed that like she can barely crawl into a bath.
Yeah, it's really so.
It's hard to watch.
That was a one timer for me. Yeah, not the kind of movie you watch over and over. But Lars Lars von Trier can make a great, great plack and I love Kirstend She's great for sure.
So we should say that you rarely will get an enema when you present yourself to a physician and are diagnosed with clinical DEPRESSI major depressive disorder. Instead, they will prescribe you pills antidepressants. And the reason that they will prescribe you any depressant is because, ever since the seventies, people have kind of basically treated depression based on what's
called the biological model. And the biological model says that you're depressed because there's an imbalance of neurotransmitters chemicals in your brain, and usually they zero in on serotonin. They say you are depressed because you have low levels of serotonin. And that's been the dominant view for decades now. That's how we treat depression as based on that presumption.
Yeah, and it's accepted, and it's not like it's accepted with, you know, through gritted teeth. I think most people agree That's what most people agree on, is they don't really understand what might be the underlying issue or the mechanism behind that is. We do know like a lot of the things that may lead to depression. If you're a woman, you're more likely to get would you call it MDD?
Yeah, major depressive disorder.
Yeah, major depressive disorder if you have suffered a loss or unresolved grief, and these are things that can compound. It's not like, again, that's different than being sad about you know, losing a loved one or something like that, but it can help contribute to MDD. Same as if you suffer through a stress early in your life, that can all contribute. So we know some of those things, but we don't know that underlying mechanism that actually causes it.
And because that, we don't exactly know how antidepressants work. We know that they do work, and we know what they do, but if you really don't know the underlying cause, you can't just say like, yeah, we have antidepressants completely figured out because we know they work and we know how they function.
Yeah. So much so we have so little of a grasp on how people become depressed, especially like depressed. That studies show that people with MDD don't have aren't likely or to have lower levels of serotonin than other people, and that just throws out basically the whole premise of the biological model. And yet we know that antidepressants work,
They work better than placebo. They're definitely doing something, and we know that by design what they're doing is going in and messing with the concentration of neurotransmitters in your brain. We know they're doing that. We just don't know how that mechanism is treating the depression. We just know it works. And I guess over the years psychologists or psychiatrists and doctors have been like, let's just not ask questions.
Well, thankfully we know that's not one hundred percent true because they are still studying and trying to figure this out. There was a study that I guess you dug this one up from last year from the University of Colorado, Go Buffalo's that hypothesize that increasing well, increasing serotonin, we know that alleviate symptoms, but it's not like it's just rebalancing your brain and picking up a level that you
had that was low. They are saying from the study that maybe it's helping to repair the neuroplasticity in the brain and just sort of like their brain circuits that become just sort of stuck and lodged in that depressed state, and it helps to unstick those.
Yeah, that's a newish from what I can tell. Rival theory to the biological model. Even though it's biological itself. It's very very confusing stuff. But the idea remember you said earlier that like you differentiate you know, MDD or even just non major depression, but you know diagnosable depression from just a passing feeling of the blues right for like a day or so.
Yeah, or mood swings you might call it whatever.
Sure, So this theory basically says that thing that people normally come out of people get stuck and it just seems to get worse and worse and worse the longer you're stuck in it, or the harder you're stuck in it. So that's a I love that theory, and there's actually support for it because some of the newer, more far out treatments psychedelics in particularly like ketamine and psilocybin, they have been basically irrefutably shown to treat major depressive disorder
really well. And we know that psilocybin, for example, goes in and basically rewires your brain. So that would support the idea that it's a change in neuroplasticity that you need a pressance create that helps treat depression.
Yeah, for sure. And we also know you know you mentioned serotonin and nora epernephrine and and you know, messing or balancing out the brain chemistry. What's what's literally going on and what they're designed to do. Antidepressants that is, and we're going to talk about I guess all of them probably right by god, we are, Uh. They interfere what's what's called the synaptic transmission of these things of serotonin and norepinephrine, dopamine.
Uh.
And that transmission is is the movement of neurotransmitters from one neuron to another. They're they're they're leaping from one to another, they're talking to each other, they're getting to know one another. And it's that transmission that we know is what antidepressants affect.
Right, That's where the money is. They go to the horse's mouth, that's another word for the synapse. That's that's what we're all just call it the horse's mouth.
That's right, with the ultimate goal for all of these to increase levels of of those things usually I mean some neuro epineph and as you'll see as we talk about, but more along the lines of serotonin.
Right. Here's the twist to all that. Though neurotransmitters do all sorts of other things besides say, like regulate your mood. I think serotonin does all sorts of crazy stuff like it helps regulate sleep, digestion, nausea, blood clotting, bone growth, It does everything right, So if you start messing with the serotonin in your brain, it can also start to mess with the other functions that serotonin does. Hence side effects, and so those are something that we are still figuring
out too. But luckily that's another thing we're getting a handle on, is the side effects.
That feels like a good break point. That's a big old table setting.
Yeah, yeah, yeah. We've got a dessert knife and a butter knife.
I don't know which is, witch pal, can you help me out.
The dessert knife is a little smaller, fancy er. It's got a kind of a sharp point and that you could easily drive through the hand of the person sitting next to you at the.
Table, Well, I no, I mean when I reach for the wrong one, just give my hand a little smack.
I'll drive my dessert knife through your hand.
Have perfect? All right, Well, we'll be right back and start off with the star of the show, the SSRI. All right, so we promised to start off with SSRIs, and we're starting off with that. We're kind of gonna jump around, starting with the most frequently prescribed sort of modern version of antidepressants, and then we'll jump back in time and talk about drugs that you know, maybe your parents took, who knows, but these came around in the
mid nineteen eighties. I think the very first one to become to become available was fluoxetine in nineteen eighty eight. And we're gonna, I guess we'll say both their regular name and their trade name or trademark name, just so everyone knows kind of what we're talking about.
Yeah, so the people who take them can like be like, yeah.
Yes, fluoxetine is prozac, paroxetine is paxel, sertraline is zoloft, fluvoxamine is lubox. These are the challenge for me, I appreciate Ititalopram is selexa and why don't you take that lex lexapro for me? What is that escalopram escatala pram Oh Okay, I just had a little yes at the beginning of that.
You did fantastic. My favorite on all of them is flu voxamine.
Yeah, that's a good word.
I like all those letters together like that. It's great. Yeah, and I'm not saying the drug itself, just the GG.
Yeah. So these are the SSRIs that are going to block. They're called re uptake inhibitors, and what that means is they're going to block that that bus trip that serotonin takes back to that original cell, the pre synaptic cell, the one who sent that transmission, huh, and it leaves it floating around in that space in between. I believe that's probably you that said that's where all the action happens. Yes,
but that's in the what's called the synaptic cleft. So it sends that that serotonin out and when it comes back, instead of uptaking it or re uptaking it, it blocks that from happening. So that just means there's more of it where you need it.
They're just hanging out there like, where's my uber?
Yeah?
Exactly, So that was lame. I'm sorry, everybody.
Pretty good, it's an uber share.
There is so many other things I could have said, and I just I don't know. I couldn't come up with anything better.
You're trying to wedge ind jokes in an unfunny episode.
Okay, thank you for that.
That's what we try and do, wedgend jokes where they're not appropriate.
So that's what that's specifically what you just said. Ssriyes too, And they live up to their name essentially.
Yeah. I don't think I even read out what it stands for. Selective serotonin reuptake inhibitor or I may have, but there is I.
Think you did. But yes, So they specifically focus on serotonin and they prevent its reuptake from the synapse that senate or the neuron that scent it out right. So the great thing about SSRIs is that they work really, really, really well on most people with the fewest side effect and it's in part because they selectively target serotonin. And despite the fact that there's fewer side effects and fewer people than other types of antidepressants, some people do not
respond particularly well to it. It depends on the brand. Not necessarily the brand, but the type of drug. I mean, all of the SSRIs aren't exactly the same. So if one's not working for you, you can try another one, and another one, another one, and if that doesn't work, then you might move on to another class of antidepressants. But from what I can tell, SSRIs are essentially still today like basically the the flagship antidepressant, if there is such a thing.
Yeah, I think you're right, And I think that when it comes to getting that if you're on more than one, either that cocktail right or that single ssri correct, that is where your doctor comes into play. But that even though I've never been through this, I've been a plenty of people who have, I believe it's safe to say that's also where you come into play though as advocating for yourself in concert with your doctor.
Right for sure?
Is that a good way to say that?
It is? And patient education is a really important part of treating depression. Like it's not one of those things where you just turn up and say what you know here, treat me like you're going to be armed with a lot of stuff on how to help yourself too. And I guarantee you they're going to say, exercise every day for twenty thirty minutes a day will be one of the things that they say because it works so well,
it's crazy what it does. Yeah, And that's part of also treating things with any depressants is if you are suffering from major depressive disorder, you probably can't get yourself up in exercise, right, So on ndepressants increases the chances that you can exercise, and then that just makes it even more effective.
Yeah. I if you suffer from depression and you feel a little lost and you are a fan of comedy, I can highly highly recommend the great comedian Gary Golman. He's a comedian who has he's been around a long long time and it's not like that's his act, but he did have one tour in one sort of set where he really really dug into this and one special and then lately he wrote about it in his book, which is great. I read the book. This is all
about his childhood growing up. But lately on Instagram he has been posting just daily things he's kind of written down on a paper that helped him when he was at his darkest. And you take a walk things like that, but drilled down and got more specific and advice on if you're a friend of someone like what you can do, Like, it's really really, really helpful. So Gary Goleman's awesome, and I encourage you to check out that Instagram. As silly as that sounds, it can really help.
It doesn't sound silly at all.
Well, anytime you're like, oh, go to a social media thing and look at what this comedian said, but you know what I mean.
No, I still don't think it was Kelly. I think it was a great shout out for sure.
Good.
So a couple more things real quick on SSRIs before we move on. They have fluoxetine in particular, Prozac has a long half life. Yeah, so you can get away with just one dose, which you're like, who cares one a day? Yeah, but that actually decreases your chances of
missing a dose. So that's a good thing. And then one of the other things too is when you go to the doctor, especially if you're a kid, they start treating you with any depressants, they're going to start out really really low dose and just kind of slowly move it up and as you get adjusted to it, it cuts down on the chances of side effects, but there can be side effects with SSRIs, from anxiety to sexual dysfunction to vertigo. So I mean you need to go
into it understanding what you're facing. But a good psychiatrist or doctor will be like, Okay, let's just do this a little at a time to get you on your feet as gently as possible.
Yeah, for sure. All right, So that's a quick overview of the SSRIs and how they work. Now we're gonna move on to we're gonna jump back in time, getting the way back machine. That's fun.
Okay, let's do it.
To the nineteen fifties and sixties when tricyclic antidepressants made their debut.
Yes, those were some of the first, but not the first strangely, but these were really kind of early pioneering antidepressants that they worked on serotonin. That was kind of their goal. They were a reuptake inhibitor as well. The problem with these things are is that they weren't selective.
That's why SSRIs are just so desirable. Tricyclic antidepressants are just like, come me here a neurotransmitter and they kind of dry homp the neurotransmitter, no matter what kind of neurotransmitter it is, and prevent it from being taken back up again.
All right, there's one way to put it. All right, We're gonna name these and these again might be things you saw if you're a gen xer, you might have seen them in your in your grandparents medicine cabinet.
Even Yeah, you probably associate these names with the smell of moth balls.
That's right, exactly. Let me see here. Here's the first one. Nor nor try, nor tripetilen nor trip to Lene.
These are no SSRIs.
Jeez, I even practice these, nor trip to Lene. Why am I getting all these? That's pamelaura. How about you take the next one?
I I can't.
Yeah, sure you can.
Protelene that's the brand names even worse, ludio mil Yeah, does a prey mean? That's nord Promean is the brand name? Am a trip to lean a little bit job? Yeah, clametpramine that does not roll off the tongue. That's anapernil, and then emipremine, which is trophonil. I've never heard of any of these, but they apparently work fairly well. It's
just the side effects that are really problematic. I mean, strangely, they treat it just as well as Ssriyes, but again they treat everything, all the neurotransmitters, and because as we've seen, neurotransmitters perform more than one function in the body, they have a whole host of side effects that you just don't want it.
Yeah, I mean, yeah, we could go through them, but it sounds like one of those commercials, but you're way more likely to experience those with those than the ssries. It's also they were the tricyclic were easier to overdose on. Yeah, and you're just not going to see them a lot for depression these days. They're still around. I think orpathic
pain is something they found use for. Yeah, and if you you know, if you don't tolerate SSRIs, they might say, you know, they might pitch you a drug from the nineteen fifties.
Right that has I saw a black box warning that the FDA slapped on it that's how we can cause suicide And I was like, how how does that stuff happen? And the way that I saw it explained is that if you have like if you are if you're suicidal, and you have depression, you're thinking of suicide, you may be too immobilized to actually carry it out. A tricyclic may lift the depression just enough for you to act. And apparently there's a warning on the box that says that. So, yeah,
tricyclics don't sound particularly desirable. Yeah, but they probably saved to quite a few people. Yeah, in the fifties and sixties when they came out.
Yeah for sure. I mean that was a long time ago. So this is early sort of you know, medicine at work. Yes, we have snur eyes serotonin not just serotonin, but serotonin and nor epinephrine re uptake inhibitors. They came around in the mid nineties, so after the SSRI is a little bit after and they do exactly what you would think. They've blocked the reptake of both of those in the same way.
Yeah. And what's weird is snur eyes. You think it's better, right, Yeah, despite selectively targeting two neurotransmitters, it's basically just as good as the Ssriyes, yeah, I think they have about the same number of side effects too.
Yeah, and those are there's only a couple of those effectsor and simbalta, and in Symbalta's case, that's dueloxatine an effectsor is vin lavaccine not.
The best name ever?
Vin laugh fixine Affle scene, What just happened?
That's great man, Ben Affleck scene is duncan.
Yeah, you're right.
There's another related class called nor adrenergic and specific serratonergic. I'll bet the psychiatrists are just laughing, laughing or else they turned this off a long time ago. Yeah, but those type of antidipressants na SSA's lowercase A first, So I'm pretty sure there's no other I guess you could say not ssays. Surely people don't.
Say that NASAs.
Sure, that's even better. It's better than ben Laughic scene.
Yeah. Yeah, they came around in the what mid eighties?
Yeah, they the nassas have. They do the same thing, but they have different side effects. It's just so bizarre. Yeah, like you can experience weight gain insedation rather than say, sexual dysfunction like on a SNRI. But they're all doing the same thing. But again, none of them seem to be any better than SSRIs and SSRs have the fewest side effects. This episode is brought to you by SSRIs By.
The next thing we're going to talk about are MAOIs or monoamine. Is that right, monoamines, monoamine, oxidase inhibitors. You got all fancy and yeah, I don't think we've mentioned yet that that's what that group is called. Serotonin, norepernephrin, and dopamine are all monoamines because of the molecular structure of those things.
Yes, so I've heard ma aoi is like basically my whole life, haven't you. Uh Now, Okay, So they're this like very like widespread class of drugs, but they have a weird twist to them in that they prevent you from breaking down something called tyramine, which is an amino acid. And tyramine is great because it regulates blood pressure, but you don't want too much tyramine. It gets out of
whack and your blood pressure gets out of whack. And tyramine is present in a lot of different foods from like soy sauce to fish to sausage, age, cheese, the best cheese, and as a matter of fact, it's called the cheese reaction where people get hypertensive from taking MAOIs and accidentally eating the wrong food. So what the monoamines get broken down by is monoamine oxidase MO, and an ma AOI is a monoamine oxidase inhibitor, so it prevents
this thing from breaking down the monoamines. And that's why you can't eat age cheese.
Do you think anyone ever goes in and they're like, can I just do the SSRIs because everyone kind of knows those, right, should we name check those?
I've never heard of any of them, but sure if you want.
No, I don't feel they need to.
Well. I think what's also interesting is that it was discovered by accident.
Oh yeh, that's right. This is one where I think it was in the early nineteen fifties. They were testing drugs for TB for tuberculosis, and it was one of those deals where they said, Hey, these people over here taking this thing, they're sleeping pretty good, they have a good appetite, they're they're bouncing around the room, they seem pretty happy, and so that's that's how it was born.
They found that I think that when they gave it to patients with depression, that seventy percent of them showed an improvement. So they said, I guess we've got a new thing here.
Yeah, so I think they started in nineteen fifty eight with marsalid, the first ever m AOI antidepressant. But again, because you can't eat age cheese, people don't usually prescribed as an antidepressant anymore.
I had that cheese duck.
Sure, I mean yeah, that don't make anybody depress not being able to eat age. Jeez.
I guess now we can jump over to or should we take a break or should we cover nutraceuticals?
I think it's I think it's break time.
All right, we'll take a break and then we'll come back and talk about something that you can just get over the counter. It's called a nutriceutical.
Right after this, okay, chuck, So we started to talking about nutraceuticals, and that's just a fancy name for a supplement that you could conceivably used to treat a malady. And in this case, people have long been seeking supplements to treat depression with whether it's clinical or you know, diagnosable or passing depression. Who knows. People don't necessarily want
to take pharmaceuticals, and it's tough to blame them. So they'll follow studies and they will read about new discoveries with people poking around trying to figure out what causes depression, and very often they'll turn up some specific amino acid or something like that that they show that there's low levels of that in the brain of people with depression, and so they'll go off and test this amino acid and they'll show like, yep, actually it improves symptoms, and
then people go out and buy tons of that supplement. But the problem is in the United States, if it's a supplement, it's essentially totally unregulated, so there's no one checking out, like to make sure that the dose is the same pill to pill, that they actually have what they say they have in them, that they don't have old newspapers ground up with it. Like it's just the wild West when it comes to supplements, which makes it
really a tricky thing to treat your depression with. Even though I totally understand how somebody would not want to take pharmaceuticals if they don't.
Have to, yeah, for sure. And you know, this is a real shame because a lot of these studies on these have come back with some results that are that look pretty good. Some of them show you know, can kind of be over the all over the place. Again, maybe because it's not regulated is the reason. Because some studies show that results can can treat MDD pretty effectively.
Others show it's not any better than at placebo. They can also have side effects, so it's not like, oh, it's just a supplement, so I don't you know, I don't hear the commercial listing, you know, a laundry list of things that could go wrong then and I can buy it just over the counter, then there can be any side effects, right, But that's not true at all.
There are side effects to supplements as well, and it can you know, there have been plenty of situations where there's a supplement that becomes kind of the the all the rage, yeah, and people just start like Saint John's work used to be when people were just like, hey, Saint John's Work's the best, we just should take tons of it. And that can result in its own set of issues.
I remember that that was our parents taking Saint John's wart. Wasn't that Uh?
Yeah? I remember my parents even at one point signed up for one of the uh supplement you know, pyramid schemes. I guess no, really sort of like the Avon Lady. But it's supplements that I remember a short time. I mean, they were always trying to hustle some side gig because they were teachers. But I specifically remember when I was a kid that we just had like a house full
of this stuff for a while. And I can't remember which system or brand this was, but if someone wrote in and told me, I would be like, oh, yep, that's the one.
Yeah. I can't bring it to mind either, but I'll bet I know what you're talking about. Yeah. So, yeah, Saint John's Ward. It was all the rage in the eighties, and I think one of the other things that lent it a lot of credibility is people have been using Saint John's Wart to improve mood for probably thousands and thousands of years, if not longer.
Yeah.
The problem is is all that time through history, people weren't also taking like birth control pills or pharmaceutical antidepressants, both of which Saint John's Wart reduces the effectiveness of. You don't really want to reduce the effectiveness of your birth control pills if you're trying not to get pregnant at that time. It also breaks down It also prevents
the breakdown of antihistamines. It does all sorts of unwanted stuff, And that's just such a great stellar lesson in the problems with using a supplement to treat something like major
depressive disorder. But it's also a lesson in just how far we need to go to look into non pharmaceutical treatments for stuff and actually study them and figure out exactly how to do it and start producing that treatment as well, because you know, I think most people do prefer something that you could conceivably consider more natural than a pharmaceutical.
No, for sure.
The problem with that, though, is that it's we're not set up the United States at least isn't set up to make a trillion dollars off of Saint John's ward. It's tough to do that that as opposed to creating a new proprietary compound that that treats depression.
Yeah, for sure. So I mean that leads very nicely into psychedelics. We promised talk of those earlier with ketamine and psilocybin, and here we are they at least for ketamine that is one that is way out in front of psilocybin. As far as like official studies in the government kind of getting behind some of this stuff.
Yeah, they love K.
Yeah, they love that K. They're being tested ketamine that is as a breakthrough treatment and breakthrough as a lay or a designation rather that the FDA says, hey, where you can fast track this through the approval process because we think it has so much potential and these still though, even though like ketamine has shown a lot of promise, it's still looked at and studied as a last resort if you're resistant to other more traditional treatments.
Yeah, so the government was all about, I should say, the FDA back in twenty nineteen, they prescribed or they approved, sorry, a prescription version of ketamine called esketamine. And apparently that to ketamine i've seen compared to CBD to THC, right, there were a couple double colons in there.
If you don't a water down version.
Exactly that like say a geriatric person might take.
Yeah, exactly. They started to develop ketamine in the nineteen sixties in Belgium, and you know they've been like you said, I think arty in two thousand it's when they really started kind of looking into stuff. So it had a big jump on psilocybin. That's one that's just now starting to kind of people are starting to say, hey, you know, you know, magic mushrooms I now has a bad connotation
for a lot of people. So let's call it psilocybin, you know the medical or you know the I guess biological name, and let's let's study this stuff.
Yeah, so psilocybin is just gangbusters at treating depression. Ketamine is too. We should say also that psychiatrists are like, we need a more potent version of ketamine, so please approve that FDA. They're not, as far as I know, on the way to do that, but who knows. But psilocybin in particular, there's just study after study after study that's like, this stuff really works, and it works in
like you don't have to stay on it. You don't have to take mushrooms every day for the rest of your life, which you know, but there's only take them a couple of times, and it can have effects that last up to a year. There was a I think a Johns Hopkins study from twenty twenty two where they gave two doses of psilocybin to patients two weeks apart, and so they gave each patient a dose of psilocybin two weeks apart. They didn't just wait two weeks to
go to the next patient, I guess, is what I'm saying. Yeah, so they found that this the effects could last like a year after a year from the second dose they and the effects were like just mind blowing too as far as the I guess quantifying the symptoms of depression, right.
Yeah, do you know how what the dose was before I give this number.
I think it was like melt your face half a bag, two handfuls.
I'm very curious, but this is a I think it was a depression rating scale they were using, where twenty four was to be and seven or below was no depression. And before they had the psilocybin, they scored twenty two, an average of twenty two point eight out of twenty four as far as being severely depressed, and then afterward it went all the way down to seven point seven, which is just a scoche above no depression.
Yeah, and that seven point seven was that follow up a year later.
Yeah, that's remarkable.
Yeah, so that was twenty twenty two. I wonder if they check in with these people now, what the scores will be, you know, is it do you have to take psilocybin every two years twice over two weeks and maintain control over depression. That's it's pretty amazing. There's another study from twenty twenty four that found that psilocybin is at least as effective at treating MDD as SSRI is probably more.
Yeah, and I think they had did try to follow up those people, but they got no self service out there on Joshua Tree.
So just real quick, there's we because we'll probably go over this a little bit in the depression episode. But if you go in for treatment of depression, they're going to treat you in three different phases, two possibly, but probably three. The first is acute where you show up and you're like, I can't take this anymore. I need treatment. They're going to get you on ss or yeah, probably an SSR. They're going to get you on some antidepressant
to start. They're going to try to work their way up while also balancing getting you feeling better as soon as possible, and time was they would try an antidepressant for like four to six weeks. That was what was generally prescribed, like that's what all psychiatrists did. And if after four to six weeks there wasn't more than a twenty five percent reduction and symptoms, they would say, this
isn't working for you, let's try another one. But I guess something happened to the psychiatry zeitgeist, and now they're waiting as long as six months to give it a chance, which has got to be tough when you're suffering from major depressive disorder. But that's the acute phase and once they get a once they find an antidepressant that can manage your symptoms, you'll move into what's called the continuation phase.
That's right, and that's after remission has begun, and that is when they're trying to you know, knock down or outright eliminate the symptoms that are still sticking around and get you back to where you were before your MDD episode. After six months of that, if there's no relapse, then they may wean you down or completely off of something.
You know, it just sort of depends. Like again, like talk talk a lot to your doctor through all this stuff, so you really have a good handle on what's going on.
So I think I said most people will suffer multipolar, chronic or recurring episodes of major depressive disorder once they have one. Yeah, something like fifty to eighty five percent of people who have one will have another episode. So there's it's probable that your continuation phase will eventually turn into a maintenance phase where they'll just keep an eye on you. You'll probably keep up with say therapy or psychoanalysis or something like that, and if your episode starts to
come back, they'll put you on the antidepressant that worked before. Yeah, And this can go anywhere from a year to indefinite. Just the point is to stay on top of your symptoms so that you don't have another episode or if one starts to come along, the nipp it in the butt very quickly.
Yeah, for sure, Which kind of all leads to the question are these being prescribed too much? That's you know, you can't hardly bring this up without hearing somebody say, yeah, they're just doctors are just willing nelly prescribing this stuff to everybody, like young children all the way to senior citizens, Like they'll just throw anyone on that. And that's just a very sort of dumb down way to look at this.
There are critics who you know, have valid points about stuff, but you have to look at real numbers as far as like an increase in prescriptions. If you look at the numbers, part of it is that they are they are staying on something for longer. So if they're keeping you on something for six months rather than just switching something out at six weeks, then the numbers for that prescription are going to be higher over a six month period. So there's just a lot more nuance in those numbers.
As far as there's been a big increase, like a sweeping statement, like there's been a big increase in the number of prescriptions.
Right, Plus, if you're just counting prescriptions of antidepressants, you might miss that, say, the tricyclic antidepressants are now being prescribed for neuropathic pain, right, so that would get lumped into that as well. And yet you can totally get the viewpoint of people who are like, yeah, that probably
accounts for some of it. But dude, I saw a statistic that in the United States people ages twelve to twenty five between twenty sixteen and twenty twenty two, monthly prescriptions that antidepressants went up sixty six percent.
Yeah, I mean twenty sixteen to twenty twenty two is also a period of a lot of upheaval in the United States and starting in twenty twenty with COVID around the world, so all of that stuff comes into play for sure.
Yeah. I think from twenty twenty to twenty twenty two, if you just look in that window, especially for I think girls and women age twelve to twenty five, it went up like one hundred and fifty percent in those two years.
Kids pulled out of school in their entire social structure sometimes yep.
Yeah, yeah, So it's also possible that the stigma has been reduced, thank you gen Z around seeking treatment for mental health, talking about your mental health, so more people could be seeking help, which could lead to a higher increase in diagnoses, which would of course lead to an
increase in prescriptions. At the same time, some people are like, we're just a lot of this is just pathologizing human sadness, and we need to especially so everybody agrees basically that if you have a low level diagnosable depression that's not MDD, then you should not start out with any depressants. You should start out with lifestyle changes like changes in your diet, exercise again, getting good sleep, just stuff you can do
without pharmaceuticals. Everyone agrees except I'm sure for the pharmaceutical companies that you should not start with that for like low level depression.
Yeah. I was curious too about kids about I wondered if there was just a minimum age, and from what I found, each drug is FDA approved starting at a certain age.
What's the youngest you found?
The youngest I found was seven years old.
I would have guessed five.
Yeah, I mean that may be, but I just found seven.
So there's just a couple of other things we want to cover real quick that fall under the umbrella of antidepressants making depression worse, right, because you would probably be bewildered if you were taking any deepressants and you're like, I actually feel way worse than I did before. And there's a whole kind of little suite of possible reasons for why that might happen.
Yeah, I mean, you may be just may be simple misdiagnosis. It could be bipolar disorder. It could be BPD, which we've talked about borderline personality disorder h but those are not the same things. So you just might be misdiagnosed.
Yeah, you might have a chump for a doctor. Yeah, genetics is also one apparently that also determines whether you have whether a risk factor like you said earlier, like grief or something like that pushes you into major depressive disorder. There's a gene, the SLC sixty four a, the serotonin transporter gene. I think there's a variation in that where you can actually get feel worse after taking an adepressants because of that gene.
Yeah, your metabolism might affect it if some people just don't clear drugs out of their system as quickly. Yeah, so if it's taking longer than usual then it usually a dose adjustment can help with that, but that could imbalance things even more.
Yeah, and then being under twenty five before your brain is fully developed, that's one. There's something called acathesia, which it's basically just an internal restlessness that keeps you from sleeping, makes you anxious, and then those will make your depression symptoms worse. And then just being on too many drugs, right.
Yeah. Polypharmacy pretty good band name, but not a great thing to live with, because, you know things, interacting with other drugs is a real thing, and if you're on a lot of them, then it's some kind sometimes can be hard to even tell what might be affecting what you had to get at a certain point.
Right, exactly. So that's it for antidepressants, right, you got anything else?
Got nothing else?
Okay, Well, go forth and seek treatment. If you have depression, especially if you think you have major depressive disorder, go get help. Things can get a lot better. And since I said things can get a lot better, everybody, it's time for a listener.
Mayw This is one of a couple I'm going to read in the next few episodes about the inner monologue episode. We heard a lot from people about that. Yeah, and specifically in this case, my inner monologue when I'm falling asleep getting really weird. Hey, guys, Chuck mentioned before falling asleep with his thoughts start to get weird, and that's how he knows he's falling asleep right away. A newt he was talking about. And the reason I read this one because I had and dozens of people that have
the same thing. Right, It's because it's very common, but this person names it. There's a term called hypnagogic imagery, which I think we've talked about that in something It might have been lucid dreaming, which I learned about from Jeff Warren's awesome book of the head Trip. It's basically the stage before falling asleep, when our brains start to produce hallucination like images. This happens to me, though I'm not consciously aware of it on nights when I fall
asleep quickly. Often I'll drift into the hypnagogic stage and then catch myself and think that was weird, which is what happens to me, and then drift back in. Chuck described his experience as a series of nonsensical thoughts, so I wonder if his is truly verbal versus visual. I would love to hear more. I think mine are a little bit of both. Jill and that is Jill in Connecticut.
Thanks Jill, that was a great one. We'd love naming stuff that we experience and didn't know there was a name for right right, So okay, Well, if you want to be like Jill, send us an email. Send it off to stuff podcast at iHeartRadio dot com.
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