WEBVTT - How Antidepressants Work 0:00:01.440 --> 0:00:07.720 Welcome to Stuff You Should Know, a production of iHeartRadio. 0:00:11.160 --> 0:00:13.720 Hey, and welcome to the podcast. I'm Josh, and there's 0:00:13.840 --> 0:00:16.919 Chuck and Jerry's here too. Well. Actually, that's not true, 0:00:17.000 --> 0:00:19.320 isn't it. It's a dirty, dirty lie. 0:00:19.280 --> 0:00:19.959 You're talking about. 0:00:19.960 --> 0:00:25.320 It's just me and Chuck. We're producing our own jam today. 0:00:25.360 --> 0:00:27.520 I guess you could say, and this is stuff you 0:00:27.520 --> 0:00:27.960 should know. 0:00:28.360 --> 0:00:31.640 That's right, and the listener will never hear where we 0:00:31.760 --> 0:00:34.520 edit out when Jerry burst into the room in two minutes. 0:00:36.080 --> 0:00:37.840 We'll just cut that out nice and clean. 0:00:38.200 --> 0:00:40.280 We should just leave it in once, just a really 0:00:40.440 --> 0:00:40.960 kind shure. 0:00:41.200 --> 0:00:42.360 Yeah, guys. 0:00:42.440 --> 0:00:46.559 Uh, she's got like a little bit of miso in 0:00:46.560 --> 0:00:47.400 the corner of her mouth. 0:00:47.479 --> 0:00:49.280 Oh, always a little crusty miso. 0:00:50.280 --> 0:00:55.200 So Chuck. Today, we are doing something in grand Stuff 0:00:55.240 --> 0:01:02.400 you should Know Fashion. We're doing a tangential episode where 0:01:02.640 --> 0:01:06.160 we haven't done like the core episode that it relates to. 0:01:06.920 --> 0:01:09.000 Have We never done one on depression. 0:01:09.360 --> 0:01:13.000 Actually, I could not believe. I looked on the stat 0:01:13.080 --> 0:01:17.080 sheet maintained by Jill Hurley, which is infallible. I looked 0:01:17.120 --> 0:01:21.240 all over the internet. I sat there and had a 0:01:21.240 --> 0:01:25.559 conversation with myself. Nothing. It's not there. 0:01:26.959 --> 0:01:29.440 Yeah. I mean that's so like us to hit stuff 0:01:29.440 --> 0:01:30.440 like bipolar first. 0:01:31.360 --> 0:01:34.119 Yeah. Yeah, we did do bipolar, we've done PTSD, we've 0:01:34.120 --> 0:01:39.440 done ADHD obviously all that, but we'll definitely do depression 0:01:39.520 --> 0:01:40.119 at some point. 0:01:41.200 --> 0:01:43.839 Okay, I think it makes sense maybe to cover this first. 0:01:44.080 --> 0:01:45.120 So how about that? 0:01:46.040 --> 0:01:47.480 Sure? Think it to me? 0:01:47.680 --> 0:01:50.400 Yeah, put that in your paulm and wash it down 0:01:50.400 --> 0:01:53.440 with some water. How's that for a segue? 0:01:53.640 --> 0:01:55.600 Oh that was a good one. That was great man. 0:01:56.120 --> 0:01:59.280 So yeah, we're talking about antidepressants. That was a great one. 0:01:59.600 --> 0:01:59.880 Thanks. 0:02:00.320 --> 0:02:03.080 And to talk about antidepressants, we really do have to 0:02:03.120 --> 0:02:05.240 kind of give at least the briefest overview of what 0:02:05.320 --> 0:02:06.040 depression is. 0:02:06.160 --> 0:02:06.240 Like. 0:02:08.120 --> 0:02:11.960 It's kind of everywhere. I saw something like sixty million 0:02:12.240 --> 0:02:15.880 adults in America and I think they define that over 0:02:15.960 --> 0:02:19.480 age eighteen these days for this kind of stuff have 0:02:19.840 --> 0:02:27.760 some sort of diagnosed depression. I think twenty million of 0:02:27.800 --> 0:02:33.120 those have major depressive disorder, which also is called clinical 0:02:33.160 --> 0:02:37.440 depression or unipolar depression, as opposed to say, like bipolar 0:02:37.480 --> 0:02:41.560 where you have ups and downs, mania and depression unipolars 0:02:41.639 --> 0:02:45.880 like just depression. And it apparently is picking up so 0:02:46.040 --> 0:02:49.440 much that the World Health Organization is saying like, hey, guys, 0:02:49.800 --> 0:02:54.000 by twenty thirty, that will be the leading disease essentially 0:02:54.080 --> 0:02:57.399 in the entire world. Depression will be just the way 0:02:57.440 --> 0:03:00.160 that things are going and everyone in the world. I 0:03:00.200 --> 0:03:03.800 was like, yeah, you know, and it just kind of 0:03:03.880 --> 0:03:04.760 is going from there. 0:03:05.200 --> 0:03:08.919 Yeah, I mean, that's a good overview, you know, without 0:03:08.919 --> 0:03:13.079 getting into the weeds as far as numbers go. Symptoms 0:03:14.040 --> 0:03:22.120 as you might imagine are they're sad, disrupted sleep, feeling 0:03:22.320 --> 0:03:27.360 like you're worthless. Sometimes it affects your concentration. Sometimes it 0:03:27.360 --> 0:03:32.080 affects your ability to even experience pleasure at all. Even 0:03:32.120 --> 0:03:36.080 you know, when you're you know, doing something that might 0:03:36.200 --> 0:03:40.040 ordinarily be fun for you, it's not fun. It's not 0:03:41.240 --> 0:03:44.040 being sad in a moment or being blue for a 0:03:44.040 --> 0:03:48.840 little while. It is a persistent thing where it disrupts 0:03:48.880 --> 0:03:51.360 your life. It interferes with your life. It can interfere 0:03:51.400 --> 0:03:55.040 with your relationships and interfere with your relationship with yourself 0:03:55.080 --> 0:03:55.880 in a big, big way. 0:03:56.480 --> 0:03:58.920 Yeah, and for a lot of people, I think for 0:03:59.040 --> 0:04:04.520 most people, statistically speaking, it's chronic or recurring. You don't 0:04:04.560 --> 0:04:07.600 just have one episode. It can keep coming back and back, 0:04:08.760 --> 0:04:11.640 and it's nothing new like depression is not new, although 0:04:11.680 --> 0:04:14.080 it does it has really kind of picked up as 0:04:14.080 --> 0:04:17.440 far as diagnoses and prescriptions go. But I mean, we 0:04:17.520 --> 0:04:20.719 used to call it melancholy and they associated it with 0:04:20.839 --> 0:04:25.400 black bile all the way back to Hippocrates. And depending 0:04:25.400 --> 0:04:28.360 on what culture you were from, they would either say 0:04:29.240 --> 0:04:32.280 tell you that you needed positive rewards. It's say you 0:04:32.360 --> 0:04:35.680 lived in Persia in the ninth century, or if you 0:04:35.800 --> 0:04:38.760 were in medieval Europe, they might burn you at the 0:04:38.800 --> 0:04:42.560 stake or something like that. Luckily, we've come a long 0:04:42.600 --> 0:04:46.440 way with treating depression. That's the that's I think we 0:04:46.440 --> 0:04:48.840 should say here at the outset. That's the message we're 0:04:48.839 --> 0:04:52.400 trying to say, like it is highly treatable. Like if 0:04:52.440 --> 0:04:55.200 you have depression and you're you're not treating it, there's 0:04:55.760 --> 0:04:59.719 definitely hope, So please don't feel like there's not. There's 0:04:59.760 --> 0:05:02.279 plenty any of hope that if anything, hopefully. That's what 0:05:02.360 --> 0:05:06.720 we get across this in this episode. But there used 0:05:06.760 --> 0:05:08.680 to be they used to give people edemas, they used 0:05:08.720 --> 0:05:13.640 to give people baths, positive thinking, diet, exercise, And what's interesting, 0:05:13.720 --> 0:05:16.760 Chuck is some of those are still prescribed today. Depending 0:05:16.800 --> 0:05:18.080 on the severity of your. 0:05:17.960 --> 0:05:22.240 Depression, yeah, for sure, and those things very much help. 0:05:22.360 --> 0:05:24.359 And I'm glad you said that what you said just 0:05:24.400 --> 0:05:27.640 a second ago, because when I said, I sounded very 0:05:27.760 --> 0:05:31.039 very down when I said that the symptoms are and 0:05:31.120 --> 0:05:34.200 I pause and just said sad. There is a lot 0:05:34.200 --> 0:05:37.840 of hope. But you know, I have everybody you know 0:05:38.480 --> 0:05:41.279 has if they don't suffer from the depression. You have 0:05:41.360 --> 0:05:43.359 people in your life and your family and your friends 0:05:44.040 --> 0:05:46.720 that do it. And it makes me very sad because 0:05:46.800 --> 0:05:51.160 these are, you know, great people who have a hill 0:05:51.240 --> 0:05:54.520 they need to consistently hike up. And I imagine it 0:05:55.279 --> 0:05:59.760 is something that drains your life force. And we're here 0:05:59.760 --> 0:06:01.640 to talk talk about some of the ways that you 0:06:01.680 --> 0:06:02.279 can change that. 0:06:03.000 --> 0:06:06.560 Yeah, just as an aside, every time I think of 0:06:06.680 --> 0:06:11.800 depression being like really accurately portrayed, I think of Kirsten 0:06:11.920 --> 0:06:15.880 Dunst in Melancholia, the large von Trier movie. Yeah, Lars 0:06:15.960 --> 0:06:18.360 von Trier, of all people, seems to have most accurately 0:06:18.839 --> 0:06:23.000 portrayed clinical depression in that movie. It is a great movie, 0:06:23.000 --> 0:06:26.120 but she just does an amazing job. Like there's a 0:06:26.120 --> 0:06:30.000 part where she's just in physical pain, such physical pain 0:06:30.640 --> 0:06:34.200 from being so depressed that like she can barely crawl 0:06:34.200 --> 0:06:35.360 into a bath. 0:06:36.000 --> 0:06:37.160 Yeah, it's really so. 0:06:37.120 --> 0:06:37.960 It's hard to watch. 0:06:38.160 --> 0:06:41.599 That was a one timer for me. Yeah, not the 0:06:41.680 --> 0:06:44.559 kind of movie you watch over and over. But Lars 0:06:45.320 --> 0:06:47.479 Lars von Trier can make a great, great plack and 0:06:47.480 --> 0:06:49.560 I love Kirstend She's great for sure. 0:06:50.480 --> 0:06:53.600 So we should say that you rarely will get an 0:06:53.680 --> 0:06:56.960 enema when you present yourself to a physician and are 0:06:57.000 --> 0:07:03.640 diagnosed with clinical DEPRESSI major depressive disorder. Instead, they will 0:07:03.760 --> 0:07:07.560 prescribe you pills antidepressants. And the reason that they will 0:07:07.600 --> 0:07:10.360 prescribe you any depressant is because, ever since the seventies, 0:07:10.800 --> 0:07:15.240 people have kind of basically treated depression based on what's 0:07:15.240 --> 0:07:19.120 called the biological model. And the biological model says that 0:07:19.600 --> 0:07:24.360 you're depressed because there's an imbalance of neurotransmitters chemicals in 0:07:24.400 --> 0:07:28.920 your brain, and usually they zero in on serotonin. They 0:07:28.960 --> 0:07:32.960 say you are depressed because you have low levels of serotonin. 0:07:33.200 --> 0:07:37.520 And that's been the dominant view for decades now. That's 0:07:37.560 --> 0:07:40.120 how we treat depression as based on that presumption. 0:07:40.680 --> 0:07:43.960 Yeah, and it's accepted, and it's not like it's accepted with, 0:07:44.080 --> 0:07:46.680 you know, through gritted teeth. I think most people agree 0:07:46.720 --> 0:07:49.920 That's what most people agree on, is they don't really 0:07:50.000 --> 0:07:54.200 understand what might be the underlying issue or the mechanism 0:07:54.240 --> 0:07:58.560 behind that is. We do know like a lot of 0:07:58.560 --> 0:08:03.280 the things that may lead to depression. If you're a woman, 0:08:03.320 --> 0:08:06.800 you're more likely to get would you call it MDD? 0:08:07.600 --> 0:08:09.880 Yeah, major depressive disorder. 0:08:09.680 --> 0:08:13.559 Yeah, major depressive disorder if you have suffered a loss 0:08:13.640 --> 0:08:16.960 or unresolved grief, and these are things that can compound. 0:08:17.000 --> 0:08:19.840 It's not like, again, that's different than being sad about 0:08:20.040 --> 0:08:22.240 you know, losing a loved one or something like that, 0:08:23.240 --> 0:08:25.800 but it can help contribute to MDD. Same as if 0:08:25.840 --> 0:08:28.640 you suffer through a stress early in your life, that 0:08:28.680 --> 0:08:31.360 can all contribute. So we know some of those things, 0:08:31.360 --> 0:08:35.600 but we don't know that underlying mechanism that actually causes it. 0:08:35.679 --> 0:08:40.600 And because that, we don't exactly know how antidepressants work. 0:08:41.559 --> 0:08:43.320 We know that they do work, and we know what 0:08:43.360 --> 0:08:46.320 they do, but if you really don't know the underlying cause, 0:08:47.040 --> 0:08:49.760 you can't just say like, yeah, we have antidepressants completely 0:08:49.760 --> 0:08:51.480 figured out because we know they work and we know 0:08:51.840 --> 0:08:52.560 how they function. 0:08:53.160 --> 0:08:55.120 Yeah. So much so we have so little of a 0:08:55.160 --> 0:09:02.880 grasp on how people become depressed, especially like depressed. That 0:09:03.880 --> 0:09:07.960 studies show that people with MDD don't have aren't likely 0:09:08.080 --> 0:09:12.160 or to have lower levels of serotonin than other people, 0:09:13.640 --> 0:09:16.520 and that just throws out basically the whole premise of 0:09:16.559 --> 0:09:20.800 the biological model. And yet we know that antidepressants work, 0:09:20.840 --> 0:09:24.360 They work better than placebo. They're definitely doing something, and 0:09:24.400 --> 0:09:27.480 we know that by design what they're doing is going 0:09:27.520 --> 0:09:32.720 in and messing with the concentration of neurotransmitters in your brain. 0:09:33.240 --> 0:09:35.560 We know they're doing that. We just don't know how 0:09:35.679 --> 0:09:40.040 that mechanism is treating the depression. We just know it works. 0:09:40.400 --> 0:09:45.840 And I guess over the years psychologists or psychiatrists and 0:09:45.960 --> 0:09:48.559 doctors have been like, let's just not ask questions. 0:09:48.880 --> 0:09:53.440 Well, thankfully we know that's not one hundred percent true 0:09:53.440 --> 0:09:55.840 because they are still studying and trying to figure this out. 0:09:56.160 --> 0:09:58.040 There was a study that I guess you dug this 0:09:58.080 --> 0:10:01.560 one up from last year from the University of Colorado, 0:10:01.760 --> 0:10:10.000 Go Buffalo's that hypothesize that increasing well, increasing serotonin, we 0:10:10.040 --> 0:10:13.760 know that alleviate symptoms, but it's not like it's just 0:10:14.240 --> 0:10:18.520 rebalancing your brain and picking up a level that you 0:10:18.640 --> 0:10:22.040 had that was low. They are saying from the study 0:10:22.440 --> 0:10:25.480 that maybe it's helping to repair the neuroplasticity in the 0:10:25.520 --> 0:10:29.480 brain and just sort of like their brain circuits that 0:10:29.559 --> 0:10:32.680 become just sort of stuck and lodged in that depressed state, 0:10:32.760 --> 0:10:34.680 and it helps to unstick those. 0:10:35.360 --> 0:10:38.360 Yeah, that's a newish from what I can tell. Rival 0:10:38.480 --> 0:10:43.760 theory to the biological model. Even though it's biological itself. 0:10:43.760 --> 0:10:47.880 It's very very confusing stuff. But the idea remember you 0:10:47.920 --> 0:10:52.720 said earlier that like you differentiate you know, MDD or 0:10:52.760 --> 0:10:57.320 even just non major depression, but you know diagnosable depression 0:10:57.640 --> 0:11:02.480 from just a passing feeling of the blues right for 0:11:02.520 --> 0:11:03.319 like a day or so. 0:11:03.440 --> 0:11:05.480 Yeah, or mood swings you might call it whatever. 0:11:05.720 --> 0:11:10.360 Sure, So this theory basically says that thing that people 0:11:10.559 --> 0:11:13.760 normally come out of people get stuck and it just 0:11:13.800 --> 0:11:15.960 seems to get worse and worse and worse the longer 0:11:16.000 --> 0:11:19.440 you're stuck in it, or the harder you're stuck in it. 0:11:19.840 --> 0:11:23.160 So that's a I love that theory, and there's actually 0:11:23.200 --> 0:11:28.280 support for it because some of the newer, more far 0:11:28.400 --> 0:11:33.640 out treatments psychedelics in particularly like ketamine and psilocybin, they 0:11:33.679 --> 0:11:40.240 have been basically irrefutably shown to treat major depressive disorder 0:11:40.559 --> 0:11:45.000 really well. And we know that psilocybin, for example, goes 0:11:45.040 --> 0:11:49.200 in and basically rewires your brain. So that would support 0:11:49.280 --> 0:11:51.959 the idea that it's a change in neuroplasticity that you 0:11:52.080 --> 0:11:55.520 need a pressance create that helps treat depression. 0:11:55.880 --> 0:11:58.840 Yeah, for sure. And we also know you know you 0:11:58.920 --> 0:12:02.640 mentioned serotonin and nora epernephrine and and you know, messing 0:12:02.720 --> 0:12:06.880 or balancing out the brain chemistry. What's what's literally going 0:12:06.920 --> 0:12:09.760 on and what they're designed to do. Antidepressants that is, 0:12:09.800 --> 0:12:11.720 and we're going to talk about I guess all of 0:12:11.720 --> 0:12:16.000 them probably right by god, we are, Uh. They interfere 0:12:16.080 --> 0:12:19.400 what's what's called the synaptic transmission of these things of 0:12:19.480 --> 0:12:21.640 serotonin and norepinephrine, dopamine. 0:12:22.160 --> 0:12:22.360 Uh. 0:12:22.400 --> 0:12:27.040 And that transmission is is the movement of neurotransmitters from 0:12:27.240 --> 0:12:30.679 one neuron to another. They're they're they're leaping from one 0:12:30.720 --> 0:12:33.520 to another, they're talking to each other, they're getting to 0:12:33.520 --> 0:12:38.000 know one another. And it's that transmission that we know 0:12:38.240 --> 0:12:40.200 is what antidepressants affect. 0:12:40.840 --> 0:12:44.080 Right, That's where the money is. They go to the 0:12:44.400 --> 0:12:49.000 horse's mouth, that's another word for the synapse. That's that's 0:12:49.000 --> 0:12:50.960 what we're all just call it the horse's mouth. 0:12:50.880 --> 0:12:52.960 That's right, with the ultimate goal for all of these 0:12:53.080 --> 0:12:58.960 to increase levels of of those things usually I mean 0:12:59.080 --> 0:13:01.520 some neuro epineph and as you'll see as we talk about, 0:13:01.880 --> 0:13:04.640 but more along the lines of serotonin. 0:13:05.360 --> 0:13:09.400 Right. Here's the twist to all that. Though neurotransmitters do 0:13:09.640 --> 0:13:13.800 all sorts of other things besides say, like regulate your mood. 0:13:14.520 --> 0:13:17.080 I think serotonin does all sorts of crazy stuff like 0:13:17.960 --> 0:13:23.120 it helps regulate sleep, digestion, nausea, blood clotting, bone growth, 0:13:23.200 --> 0:13:26.439 It does everything right, So if you start messing with 0:13:26.480 --> 0:13:29.880 the serotonin in your brain, it can also start to 0:13:29.960 --> 0:13:35.640 mess with the other functions that serotonin does. Hence side effects, 0:13:35.880 --> 0:13:38.680 and so those are something that we are still figuring 0:13:38.720 --> 0:13:41.600 out too. But luckily that's another thing we're getting a 0:13:41.640 --> 0:13:43.479 handle on, is the side effects. 0:13:44.880 --> 0:13:47.040 That feels like a good break point. That's a big 0:13:47.040 --> 0:13:47.920 old table setting. 0:13:48.559 --> 0:13:52.760 Yeah, yeah, yeah. We've got a dessert knife and a 0:13:52.800 --> 0:13:53.440 butter knife. 0:13:53.720 --> 0:13:55.160 I don't know which is, witch pal, can you help 0:13:55.160 --> 0:13:55.400 me out. 0:13:55.600 --> 0:13:58.360 The dessert knife is a little smaller, fancy er. It's 0:13:58.400 --> 0:14:01.400 got a kind of a sharp point and that you 0:14:01.440 --> 0:14:04.600 could easily drive through the hand of the person sitting 0:14:04.600 --> 0:14:05.320 next to you at the. 0:14:05.320 --> 0:14:07.080 Table, Well, I no, I mean when I reach for 0:14:07.120 --> 0:14:09.160 the wrong one, just give my hand a little smack. 0:14:09.440 --> 0:14:11.280 I'll drive my dessert knife through your hand. 0:14:11.280 --> 0:14:14.280 Have perfect? All right, Well, we'll be right back and 0:14:14.800 --> 0:14:17.600 start off with the star of the show, the SSRI. 0:14:53.920 --> 0:14:56.520 All right, so we promised to start off with SSRIs, 0:14:56.560 --> 0:14:58.280 and we're starting off with that. We're kind of gonna 0:14:58.320 --> 0:15:02.720 jump around, starting with the most frequently prescribed sort of 0:15:02.760 --> 0:15:06.360 modern version of antidepressants, and then we'll jump back in 0:15:06.440 --> 0:15:10.440 time and talk about drugs that you know, maybe your 0:15:10.480 --> 0:15:14.680 parents took, who knows, but these came around in the 0:15:14.720 --> 0:15:18.640 mid nineteen eighties. I think the very first one to 0:15:18.760 --> 0:15:23.680 become to become available was fluoxetine in nineteen eighty eight. 0:15:25.480 --> 0:15:28.960 And we're gonna, I guess we'll say both their regular 0:15:29.040 --> 0:15:32.240 name and their trade name or trademark name, just so 0:15:32.280 --> 0:15:33.920 everyone knows kind of what we're talking about. 0:15:34.080 --> 0:15:36.480 Yeah, so the people who take them can like be like, yeah. 0:15:36.600 --> 0:15:45.479 Yes, fluoxetine is prozac, paroxetine is paxel, sertraline is zoloft, 0:15:46.440 --> 0:15:53.120 fluvoxamine is lubox. These are the challenge for me, I 0:15:53.160 --> 0:16:00.360 appreciate Ititalopram is selexa and why don't you take that 0:16:00.440 --> 0:16:05.280 lex lexapro for me? What is that escalopram escatala pram 0:16:05.280 --> 0:16:07.120 Oh Okay, I just had a little yes at the 0:16:07.120 --> 0:16:07.640 beginning of that. 0:16:07.920 --> 0:16:10.360 You did fantastic. My favorite on all of them is 0:16:10.440 --> 0:16:12.400 flu voxamine. 0:16:12.640 --> 0:16:13.680 Yeah, that's a good word. 0:16:14.000 --> 0:16:16.840 I like all those letters together like that. It's great. Yeah, 0:16:16.880 --> 0:16:19.280 and I'm not saying the drug itself, just the GG. 0:16:20.040 --> 0:16:23.680 Yeah. So these are the SSRIs that are going to block. 0:16:24.000 --> 0:16:26.400 They're called re uptake inhibitors, and what that means is 0:16:26.400 --> 0:16:30.640 they're going to block that that bus trip that serotonin 0:16:30.680 --> 0:16:34.160 takes back to that original cell, the pre synaptic cell, 0:16:35.000 --> 0:16:38.240 the one who sent that transmission, huh, and it leaves 0:16:38.320 --> 0:16:41.720 it floating around in that space in between. I believe 0:16:41.800 --> 0:16:45.400 that's probably you that said that's where all the action happens. Yes, 0:16:45.440 --> 0:16:48.000 but that's in the what's called the synaptic cleft. So 0:16:48.080 --> 0:16:51.720 it sends that that serotonin out and when it comes back, 0:16:51.800 --> 0:16:54.840 instead of uptaking it or re uptaking it, it blocks 0:16:54.880 --> 0:16:57.560 that from happening. So that just means there's more of 0:16:57.600 --> 0:16:58.320 it where you need it. 0:16:58.600 --> 0:17:01.040 They're just hanging out there like, where's my uber? 0:17:01.720 --> 0:17:01.960 Yeah? 0:17:02.000 --> 0:17:06.560 Exactly, So that was lame. I'm sorry, everybody. 0:17:06.800 --> 0:17:08.840 Pretty good, it's an uber share. 0:17:09.240 --> 0:17:11.520 There is so many other things I could have said, 0:17:11.560 --> 0:17:13.639 and I just I don't know. I couldn't come up 0:17:13.680 --> 0:17:14.480 with anything better. 0:17:14.760 --> 0:17:17.719 You're trying to wedge ind jokes in an unfunny episode. 0:17:17.960 --> 0:17:19.600 Okay, thank you for that. 0:17:19.600 --> 0:17:22.240 That's what we try and do, wedgend jokes where they're 0:17:22.240 --> 0:17:22.840 not appropriate. 0:17:24.000 --> 0:17:28.600 So that's what that's specifically what you just said. Ssriyes too, 0:17:28.920 --> 0:17:30.640 And they live up to their name essentially. 0:17:31.119 --> 0:17:33.199 Yeah. I don't think I even read out what it 0:17:33.240 --> 0:17:36.359 stands for. Selective serotonin reuptake inhibitor or I may have, 0:17:36.440 --> 0:17:37.720 but there is I. 0:17:37.600 --> 0:17:41.119 Think you did. But yes, So they specifically focus on 0:17:41.240 --> 0:17:45.159 serotonin and they prevent its reuptake from the synapse that 0:17:45.320 --> 0:17:49.840 senate or the neuron that scent it out right. So 0:17:50.000 --> 0:17:53.159 the great thing about SSRIs is that they work really, really, 0:17:53.280 --> 0:17:58.040 really well on most people with the fewest side effect 0:17:58.960 --> 0:18:03.199 and it's in part because they selectively target serotonin. And 0:18:03.240 --> 0:18:06.719 despite the fact that there's fewer side effects and fewer 0:18:06.760 --> 0:18:11.560 people than other types of antidepressants, some people do not 0:18:11.720 --> 0:18:16.960 respond particularly well to it. It depends on the brand. 0:18:17.720 --> 0:18:20.360 Not necessarily the brand, but the type of drug. I mean, 0:18:20.440 --> 0:18:23.640 all of the SSRIs aren't exactly the same. So if 0:18:23.680 --> 0:18:26.440 one's not working for you, you can try another one, 0:18:26.440 --> 0:18:28.520 and another one, another one, and if that doesn't work, 0:18:28.560 --> 0:18:31.840 then you might move on to another class of antidepressants. 0:18:31.840 --> 0:18:36.119 But from what I can tell, SSRIs are essentially still 0:18:36.160 --> 0:18:41.720 today like basically the the flagship antidepressant, if there is 0:18:41.760 --> 0:18:42.280 such a thing. 0:18:43.280 --> 0:18:46.720 Yeah, I think you're right, And I think that when 0:18:46.720 --> 0:18:50.440 it comes to getting that if you're on more than one, 0:18:50.520 --> 0:18:55.479 either that cocktail right or that single ssri correct, that 0:18:55.600 --> 0:18:58.120 is where your doctor comes into play. But that even 0:18:58.160 --> 0:19:00.400 though I've never been through this, I've been a plenty 0:19:00.400 --> 0:19:02.880 of people who have, I believe it's safe to say 0:19:02.920 --> 0:19:06.120 that's also where you come into play though as advocating 0:19:06.200 --> 0:19:10.679 for yourself in concert with your doctor. 0:19:10.880 --> 0:19:11.879 Right for sure? 0:19:12.040 --> 0:19:13.040 Is that a good way to say that? 0:19:13.240 --> 0:19:16.200 It is? And patient education is a really important part 0:19:16.400 --> 0:19:19.920 of treating depression. Like it's not one of those things 0:19:19.920 --> 0:19:21.920 where you just turn up and say what you know here, 0:19:22.040 --> 0:19:24.240 treat me like you're going to be armed with a 0:19:24.280 --> 0:19:26.880 lot of stuff on how to help yourself too. And 0:19:26.960 --> 0:19:30.560 I guarantee you they're going to say, exercise every day 0:19:30.600 --> 0:19:32.879 for twenty thirty minutes a day will be one of 0:19:32.880 --> 0:19:36.560 the things that they say because it works so well, 0:19:37.000 --> 0:19:40.119 it's crazy what it does. Yeah, And that's part of 0:19:40.160 --> 0:19:43.840 also treating things with any depressants is if you are 0:19:44.280 --> 0:19:48.760 suffering from major depressive disorder, you probably can't get yourself 0:19:48.840 --> 0:19:54.399 up in exercise, right, So on ndepressants increases the chances 0:19:54.400 --> 0:19:57.600 that you can exercise, and then that just makes it 0:19:57.680 --> 0:19:58.680 even more effective. 0:19:59.080 --> 0:20:02.560 Yeah. I if you suffer from depression and you feel 0:20:02.600 --> 0:20:06.760 a little lost and you are a fan of comedy, 0:20:07.640 --> 0:20:10.840 I can highly highly recommend the great comedian Gary Golman. 0:20:11.720 --> 0:20:14.040 He's a comedian who has he's been around a long 0:20:14.080 --> 0:20:16.399 long time and it's not like that's his act, but 0:20:16.880 --> 0:20:19.360 he did have one tour in one sort of set 0:20:19.400 --> 0:20:21.760 where he really really dug into this and one special 0:20:22.640 --> 0:20:25.320 and then lately he wrote about it in his book, 0:20:25.359 --> 0:20:27.560 which is great. I read the book. This is all 0:20:27.560 --> 0:20:29.960 about his childhood growing up. But lately on Instagram he 0:20:30.040 --> 0:20:34.160 has been posting just daily things he's kind of written 0:20:34.160 --> 0:20:36.280 down on a paper that helped him when he was 0:20:36.320 --> 0:20:39.920 at his darkest. And you take a walk things like that, 0:20:40.000 --> 0:20:44.639 but drilled down and got more specific and advice on 0:20:45.200 --> 0:20:47.760 if you're a friend of someone like what you can do, Like, 0:20:47.960 --> 0:20:50.719 it's really really, really helpful. So Gary Goleman's awesome, and 0:20:50.760 --> 0:20:53.560 I encourage you to check out that Instagram. As silly 0:20:53.600 --> 0:20:55.840 as that sounds, it can really help. 0:20:56.800 --> 0:20:58.040 It doesn't sound silly at all. 0:20:58.320 --> 0:21:00.680 Well, anytime you're like, oh, go to a social media 0:21:00.720 --> 0:21:02.879 thing and look at what this comedian said, but you 0:21:02.920 --> 0:21:03.520 know what I mean. 0:21:04.680 --> 0:21:06.600 No, I still don't think it was Kelly. I think 0:21:06.640 --> 0:21:08.080 it was a great shout out for sure. 0:21:08.280 --> 0:21:08.480 Good. 0:21:09.400 --> 0:21:12.040 So a couple more things real quick on SSRIs before 0:21:12.080 --> 0:21:17.320 we move on. They have fluoxetine in particular, Prozac has 0:21:17.359 --> 0:21:21.080 a long half life. Yeah, so you can get away 0:21:21.080 --> 0:21:23.280 with just one dose, which you're like, who cares one 0:21:23.320 --> 0:21:26.800 a day? Yeah, but that actually decreases your chances of 0:21:26.840 --> 0:21:29.160 missing a dose. So that's a good thing. And then 0:21:29.160 --> 0:21:31.000 one of the other things too is when you go 0:21:31.480 --> 0:21:34.280 to the doctor, especially if you're a kid, they start 0:21:34.320 --> 0:21:36.239 treating you with any depressants, they're going to start out 0:21:36.320 --> 0:21:38.880 really really low dose and just kind of slowly move 0:21:38.920 --> 0:21:41.240 it up and as you get adjusted to it, it 0:21:41.280 --> 0:21:43.960 cuts down on the chances of side effects, but there 0:21:43.960 --> 0:21:47.760 can be side effects with SSRIs, from anxiety to sexual 0:21:47.840 --> 0:21:51.840 dysfunction to vertigo. So I mean you need to go 0:21:51.960 --> 0:21:55.720 into it understanding what you're facing. But a good psychiatrist 0:21:55.880 --> 0:21:57.800 or doctor will be like, Okay, let's just do this 0:21:57.840 --> 0:22:00.600 a little at a time to get you on your 0:22:00.600 --> 0:22:02.440 feet as gently as possible. 0:22:02.760 --> 0:22:06.160 Yeah, for sure. All right, So that's a quick overview 0:22:06.200 --> 0:22:08.400 of the SSRIs and how they work. Now we're gonna 0:22:08.440 --> 0:22:12.440 move on to we're gonna jump back in time, getting 0:22:12.440 --> 0:22:13.600 the way back machine. That's fun. 0:22:13.920 --> 0:22:15.240 Okay, let's do it. 0:22:21.960 --> 0:22:27.280 To the nineteen fifties and sixties when tricyclic antidepressants made 0:22:27.320 --> 0:22:28.400 their debut. 0:22:29.840 --> 0:22:32.840 Yes, those were some of the first, but not the 0:22:32.840 --> 0:22:38.119 first strangely, but these were really kind of early pioneering 0:22:39.200 --> 0:22:43.280 antidepressants that they worked on serotonin. That was kind of 0:22:43.320 --> 0:22:48.199 their goal. They were a reuptake inhibitor as well. The 0:22:48.359 --> 0:22:53.520 problem with these things are is that they weren't selective. 0:22:54.080 --> 0:22:58.840 That's why SSRIs are just so desirable. Tricyclic antidepressants are 0:22:58.880 --> 0:23:02.400 just like, come me here a neurotransmitter and they kind 0:23:02.400 --> 0:23:05.639 of dry homp the neurotransmitter, no matter what kind of 0:23:05.640 --> 0:23:09.280 neurotransmitter it is, and prevent it from being taken back 0:23:09.359 --> 0:23:09.840 up again. 0:23:10.720 --> 0:23:13.239 All right, there's one way to put it. All right, 0:23:13.240 --> 0:23:15.680 We're gonna name these and these again might be things 0:23:15.720 --> 0:23:19.320