WEBVTT - Ep 183 SSRIs Part 2: Action 0:00:00.360 --> 0:00:02.720 Hi, I'm Haley. I'm twenty four, and this is my 0:00:02.880 --> 0:00:06.280 story with's so looft so. Growing up, I was the 0:00:06.360 --> 0:00:11.080 kid who was scared of everything. In sects, people in costumes, heights, 0:00:11.160 --> 0:00:13.920 you name it. But beneath all that fear, we're intrusive 0:00:13.920 --> 0:00:16.400 thoughts that no one else could see. For instance, my 0:00:16.440 --> 0:00:19.680 mom's allergip bees. I was constantly worried that I, rather 0:00:19.720 --> 0:00:22.880 rest would get stung and we would die. I tried 0:00:22.920 --> 0:00:25.960 to relieve these thoughts through avoidance, skin picking, and checking, 0:00:26.200 --> 0:00:29.760 with very minimal relief. I attempted to explain my fears 0:00:29.760 --> 0:00:32.880 to pediatricians and school counselors, but I was never given 0:00:32.920 --> 0:00:36.199 any real concrete answers. I began to believe this was 0:00:36.440 --> 0:00:39.479 just who I was. College is when things began to worsen. 0:00:39.960 --> 0:00:42.559 When the pandemic hit in spring of twenty twenty, my 0:00:42.600 --> 0:00:47.280 anxiety exploded. I remember obsessively locking my windows and shutting 0:00:47.280 --> 0:00:49.920 the blinds, convinced that someone'd break in or try to 0:00:49.920 --> 0:00:53.360 bring the virus inside. I was diagnosed with an adjustment 0:00:53.400 --> 0:00:55.920 disorder and was even taken off my birth control because 0:00:55.960 --> 0:00:58.880 that was believed to beet the issue. Eventually, in the 0:00:58.880 --> 0:01:00.520 fall of twenty twenty, I was able to get an 0:01:00.520 --> 0:01:04.160 appointment with our head college doctor. She truly listened and said, 0:01:04.200 --> 0:01:06.520 I think this might be an anxiety disorder, and she 0:01:06.560 --> 0:01:09.600 started me on fifty milligrams as Soloft, and for the 0:01:09.640 --> 0:01:12.440 first time, I felt like I could breathe. I had 0:01:12.560 --> 0:01:15.640 very minimal side effects, only some sleepiness and some GI 0:01:15.760 --> 0:01:18.600 upset for the first two weeks. The next fall, I 0:01:18.640 --> 0:01:21.440 began wondering if it might be OCD. I began tracking 0:01:21.440 --> 0:01:24.800 my thoughts, looking into patterns, but unfortunately, in the spring 0:01:24.800 --> 0:01:28.399 of twenty twenty two, my depression took over. My depression 0:01:28.400 --> 0:01:31.280 manifested into intrusive thoughts, telling me to hurt myself, even 0:01:31.319 --> 0:01:34.000 though I really didn't want to. I knew something was 0:01:34.040 --> 0:01:36.280 really wrong, and so I went back to my head 0:01:36.319 --> 0:01:39.080 college doctor. She increased my soul off to one hundred 0:01:39.120 --> 0:01:43.080 milligrams and that definitely helped. Still, none of my doctors 0:01:43.080 --> 0:01:47.400 felt qualified to diagnose OCD. My pediatrician later admitted she 0:01:47.440 --> 0:01:51.600 had suspected it for years. In twenty twenty four, one 0:01:51.680 --> 0:01:54.480 year out of college, I finally got my OCD diagnosis 0:01:54.480 --> 0:01:58.160 for my current therapist. My new primary caper provider was 0:01:58.200 --> 0:02:00.240 really thrilled to hear this and one defy me a 0:02:00.280 --> 0:02:05.000 regimen that worked. So typically for OCD, you give the 0:02:05.080 --> 0:02:09.920 patient a top dose of their preferred SSRI, but for me, 0:02:10.040 --> 0:02:12.600 she kept me on my one hundred milligrams of zolof 0:02:12.639 --> 0:02:15.680 and added a dose abuse bar and that worked for me. 0:02:15.840 --> 0:02:17.960 In my thoughts got quieter and I was able to 0:02:18.120 --> 0:02:23.559 finally start making progress again in my OCD therapy. SSRIs 0:02:23.560 --> 0:02:26.639 have truly changed my life. I used to spend every 0:02:26.720 --> 0:02:29.560 day fighting my own mind, and now I'm able to 0:02:29.600 --> 0:02:31.960 achieve goals that I had set for years, such as 0:02:32.000 --> 0:02:35.119 applying to medical school. I'm really lucky to have had 0:02:35.360 --> 0:02:37.480 very few side effects and not have to go through 0:02:37.520 --> 0:02:41.160 many different medications. I really cannot imagine going back to 0:02:41.200 --> 0:02:45.400 a life where I was not on SSRIs. They don't 0:02:45.440 --> 0:02:48.120 just help me function, they have given me back my future. 0:02:50.240 --> 0:02:55.000 My name is Sarah, and I started using SSRIs during 0:02:55.120 --> 0:02:59.679 my master's degree over ten years ago now. So, while 0:02:59.680 --> 0:03:03.000 I was sudying for my masters, I started to experience 0:03:03.040 --> 0:03:07.960 really profound anxiety and a lot of obsessive thinking. I 0:03:08.000 --> 0:03:11.000 became convinced that I had plagiarized all the work I'd 0:03:11.000 --> 0:03:15.280 ever done and that ireparably harmed every person I'd ever encountered, 0:03:16.120 --> 0:03:21.840 and I spent all day a lot of days, checking 0:03:21.840 --> 0:03:25.440 my work and seeking reassurance or reaching out to apologize 0:03:25.440 --> 0:03:29.480 to people for things I imagined i'd done. I was 0:03:29.520 --> 0:03:34.400 diagnosed with obsessive compulsive disorder and originally tried to manage 0:03:34.400 --> 0:03:38.440 it with just cognitive behavioral therapy, which helped a bit, 0:03:39.040 --> 0:03:43.800 but it reached the point where I was very unmanaged 0:03:43.960 --> 0:03:48.440 and was having suicidal ideation and thinking I had to 0:03:48.520 --> 0:03:52.320 drop out of school. So I began to use an SSRI, 0:03:53.240 --> 0:03:55.320 and after the first few weeks when it started to 0:03:55.360 --> 0:04:01.040 take effect, I had this amazing experience of that used 0:04:01.080 --> 0:04:03.800 to be thoughts that I would obsess over and would 0:04:03.880 --> 0:04:06.840 ruin my week because I would spend all of my 0:04:07.000 --> 0:04:12.080 time in service of those obsessions. Now, as the SSRIs 0:04:12.120 --> 0:04:15.000 kicked in, my brain would just sort of slide off 0:04:15.000 --> 0:04:17.159 of those thoughts and I could go on to do 0:04:17.320 --> 0:04:21.600 other things that day, and it was really wonderful. So 0:04:21.839 --> 0:04:24.920 with that under control, I was able to complete my 0:04:25.160 --> 0:04:29.440 master's degree and publish some work from that, and after 0:04:29.480 --> 0:04:32.240 several years of being under good control, I've been able 0:04:32.320 --> 0:04:36.520 to start studying for my PhD. So I'm very fortunate 0:04:36.680 --> 0:04:40.480 that for me, SSRIs have not had substantial negative side 0:04:40.480 --> 0:04:44.840 effects and that they've been effective and helpful. And because 0:04:44.880 --> 0:04:48.440 of that, I've been able to really enjoy my work 0:04:48.880 --> 0:04:53.280 and do research that I think is significant and impactful 0:04:53.480 --> 0:04:56.720 for the world, while actually getting joy from that instead 0:04:56.720 --> 0:05:35.360 of just anxiety. 0:05:44.160 --> 0:05:47.200 Thank you so much for sharing your first hand account 0:05:47.279 --> 0:05:49.560 that it really means. It means the world to us. 0:05:49.600 --> 0:05:53.840 It's so important to have that that personal experience to 0:05:54.960 --> 0:05:59.440 learn from and to get an insight into how SSRIs 0:05:59.640 --> 0:06:02.479 work or don't work, or just the impact that they've had. 0:06:02.800 --> 0:06:06.720 Yeah, it's not something that we can convey by ourselves, 0:06:06.720 --> 0:06:09.320 So thank you for sharing with us. And thank you 0:06:09.360 --> 0:06:11.159 to everybody who wrote in. I know a lot of 0:06:11.200 --> 0:06:15.599 you did, and we really really appreciate everyone's willingness to 0:06:15.680 --> 0:06:18.279 just share your story with us. That's not an easy 0:06:18.279 --> 0:06:19.840 thing to do and it means so much. 0:06:20.040 --> 0:06:20.880 So it really does. 0:06:21.720 --> 0:06:21.920 Hi. 0:06:22.200 --> 0:06:25.160 I'm Aaron Welsh and I'm Erin aman Updike. 0:06:25.040 --> 0:06:27.200 And this is this podcast will Kill You. 0:06:27.560 --> 0:06:32.440 We're back as promised, we are with part two of SSRIs. 0:06:34.560 --> 0:06:38.960 How do they work? What are they? What is serotonin 0:06:39.480 --> 0:06:42.560 besides something that does everything. 0:06:43.920 --> 0:06:45.680 I mean, you told us a lot about that, Aaron, 0:06:45.760 --> 0:06:47.160 Let's be honest, but. 0:06:47.120 --> 0:06:49.880 Like I was just like, and it does these things? Yeah? 0:06:49.880 --> 0:06:51.360 How does it do those things? Oh? 0:06:51.960 --> 0:06:56.000 I'm not going to get into that, Aaron. Watch this 0:06:56.200 --> 0:06:57.880 not be at all what you wanted to learn in 0:06:57.880 --> 0:07:00.360 this episode. But that's okay. We're going to have fun regardless. 0:07:00.480 --> 0:07:03.000 I'm a blank slate. I'm happy to learn anything. 0:07:03.160 --> 0:07:08.320 If you we do. If you missed last week's episode, 0:07:08.560 --> 0:07:11.400 do check it out. Aaron welshwak just through the history 0:07:11.520 --> 0:07:14.280 of serotonin. How did we even figure out it was 0:07:14.360 --> 0:07:19.120 a thing? Wow? And how we came up with ssriyes, 0:07:19.600 --> 0:07:22.600 and how pharmaceuticals have advertised them. 0:07:22.720 --> 0:07:23.440 Yeah. 0:07:24.160 --> 0:07:27.120 Yeah, And then today we're gonna we're gonna take it 0:07:27.160 --> 0:07:27.480 from there. 0:07:27.920 --> 0:07:36.160 Love it short and sweet. But first we are drinking 0:07:36.160 --> 0:07:38.160 the same thing that we did last week for our 0:07:38.240 --> 0:07:43.080 quarantiny really Placey Brita time the serotonin sprits, serotonin sprints, 0:07:43.200 --> 0:07:48.160 apple cider and pineapple juice and soda water and it's 0:07:48.200 --> 0:07:50.200 simple and freshing. 0:07:51.320 --> 0:07:53.239 Enjoy it's online. 0:07:53.600 --> 0:07:56.960 Check it out. Check it out. I feel like I've 0:07:57.000 --> 0:07:59.200 been forcing you to do the website just by being like, 0:07:59.600 --> 0:08:02.080 what do we do now? So I'll do the website. 0:08:02.080 --> 0:08:02.680 Okay, great. 0:08:04.240 --> 0:08:06.680 You can find lots of things on our website This 0:08:06.720 --> 0:08:09.440 podcast will kill You dot com. You can find things 0:08:09.480 --> 0:08:12.000 related to our sources for each and every one of 0:08:12.040 --> 0:08:14.960 our episodes. We've got links to bookshop dot org, affiliate account, 0:08:14.960 --> 0:08:17.800 our Goodreads list, links to merch links to Patreon, links 0:08:17.800 --> 0:08:21.960 to music by bloodmobile transcripts, a contact us form, and 0:08:23.000 --> 0:08:23.720 more things. 0:08:24.000 --> 0:08:27.360 I loved it and I also love when you go 0:08:27.440 --> 0:08:28.760 into your like semi. 0:08:28.440 --> 0:08:32.120 Newscasters caster voice. Yeah, I know. My secret dream is 0:08:32.160 --> 0:08:35.280 to be like just a voice on the on the TV, 0:08:35.520 --> 0:08:39.120 on the documentary and look of a voice actor blah 0:08:39.160 --> 0:08:40.600 blah blah. Yeah, wouldn't it be nice? 0:08:40.679 --> 0:08:40.880 Yeah? 0:08:40.880 --> 0:08:41.760 I have a training for that. 0:08:42.120 --> 0:08:43.320 Anyone anyone hiring? 0:08:43.640 --> 0:08:46.319 Yeah, please let me know. Reach out this podcast will 0:08:46.360 --> 0:08:47.920 Kill You dot com on the contact us form on 0:08:47.960 --> 0:08:49.800 our website. 0:08:52.679 --> 0:08:55.000 If you haven't already rated, reviewed, and subscribed on your 0:08:55.000 --> 0:08:57.600 favorite podcast here, are you listening on iHeart Podcasts? Are 0:08:57.600 --> 0:08:59.840 you listening on Apple podcasts? Are you listening on Spotify? 0:09:00.280 --> 0:09:02.840 Check the subscribe button and make sure that you clicked 0:09:03.080 --> 0:09:08.400 down on it and that you left us a rating 0:09:08.600 --> 0:09:10.560 or a review. If you like us. If you don't, 0:09:10.600 --> 0:09:13.360 you don't have to do that part. You can unsubscribe. 0:09:13.400 --> 0:09:16.440 In fact, the visuals, just so you know, are very 0:09:16.480 --> 0:09:19.199 good for what Erin is currently doing, and so if 0:09:19.200 --> 0:09:23.000 you are so inclined, you can see them on YouTube. 0:09:23.360 --> 0:09:27.480 If you want to watch the video for these podcast episode. 0:09:27.000 --> 0:09:30.040 You can follow the exactly Right network channel on YouTube. 0:09:30.559 --> 0:09:31.920 Yep, the end. 0:09:32.000 --> 0:09:33.200 Shall we start now? 0:09:33.640 --> 0:09:36.120 I believe that we shall. Okay, take a quick break 0:09:36.160 --> 0:09:37.360 and get started. 0:09:37.480 --> 0:09:58.720 Okay, So Erin, Erin, you walked us through last week, 0:09:59.000 --> 0:10:05.040 so beautiful about what we know about, like how serotonin, 0:10:05.120 --> 0:10:07.280 like where it came from, how long it's been with us, 0:10:07.600 --> 0:10:11.920 how we came to find SSRIs intentionally, which is so interesting, 0:10:13.040 --> 0:10:15.920 and some of the issues with how we have marketed 0:10:15.960 --> 0:10:18.680 them and how we think about in like the popular 0:10:18.760 --> 0:10:22.920 media sense, how we think about how they work, which 0:10:22.960 --> 0:10:25.960 I think has led to a lot of the controversies 0:10:26.400 --> 0:10:28.600 that come with SSRIs today, though there's a lot of 0:10:28.600 --> 0:10:31.480 other reasons for that, which I'll get into. So I 0:10:31.520 --> 0:10:34.839 want to start by just setting the stage for what 0:10:35.000 --> 0:10:38.520 I am actually going to cover today, because it's a 0:10:38.559 --> 0:10:41.079 lot of things and not a lot of things at 0:10:41.080 --> 0:10:44.800 the same time, huh. I'm tempering expectations. That's what I'm doing. 0:10:46.880 --> 0:10:48.839 I will not just end with we don't know how 0:10:48.840 --> 0:10:52.360 these work, Okay, Okay, though I will probably still say 0:10:52.400 --> 0:10:56.080 that a lot of times as usual. But this is 0:10:56.120 --> 0:10:59.360 not an episode where I dive deep into the neurobiology 0:10:59.360 --> 0:11:03.319 of depression or anxiety, because those are topics that deserve 0:11:03.679 --> 0:11:07.000 their own episodes, definitely, and we'll have them at some point. 0:11:08.000 --> 0:11:11.080 I Am not going to get super nitty gritty on 0:11:11.679 --> 0:11:15.600 the five HT one A autoreceptor blah blah blah. Like 0:11:15.720 --> 0:11:19.880 we're talking. There are so many serotonin receptors and I'm 0:11:19.880 --> 0:11:23.040 not gonna I'm not gonna get us, you know, up 0:11:23.080 --> 0:11:26.520 to our eyeballs in it. Okay, okay, But my goal 0:11:26.800 --> 0:11:30.280 is to give us all a real sense of how 0:11:30.360 --> 0:11:33.800 we actually use SSRIs today, Like how are they used 0:11:33.800 --> 0:11:37.640 in kind of clinical practice? How are they thought of? 0:11:38.080 --> 0:11:41.720 Not in social media circles or political circles or popular 0:11:41.720 --> 0:11:44.000 media circles, but how are they thought of by the 0:11:44.040 --> 0:11:48.679 medical and scientific communities that use them and that research them. 0:11:49.040 --> 0:11:52.360 What do we think that we know about how they 0:11:52.360 --> 0:11:56.400 are treating the disorders that we use them for? Are 0:11:56.440 --> 0:11:59.320 they effective? And what does that mean. 0:12:00.080 --> 0:12:01.840 What does that mean? Okay? 0:12:02.400 --> 0:12:04.600 Yeah, and then hopefully do a little bit of like 0:12:04.720 --> 0:12:08.080 myth busting and a little bit of like grounding of 0:12:08.320 --> 0:12:12.320 big picture. How do these conversations that we're having about 0:12:12.360 --> 0:12:15.080 SSRIs tell us about the way that we think about 0:12:15.160 --> 0:12:21.079 mental health conditions as a society. Oh, small feet ready? Yeah, 0:12:21.160 --> 0:12:26.840 So SSRIs, selective serotonin re uptake inhibitors are considered one 0:12:26.880 --> 0:12:32.080 of the possible first line therapies for both depressive disorders, 0:12:32.200 --> 0:12:35.440 which there are a lot of depressive disorders. There's major 0:12:35.480 --> 0:12:40.080 depressive disorder or MDD, but there's others. There's persistent depressive disorder, 0:12:40.200 --> 0:12:43.839 there's design yet like there are a lot, Okay, and 0:12:44.240 --> 0:12:47.559 also first line one of the possible first line therapies 0:12:47.600 --> 0:12:52.440 for anxiety disorders, of which there are many, Generalized anxiety disorder, 0:12:52.640 --> 0:12:59.240 Social anxiety disorder PTSD, OCD and more. If anyone listening 0:12:59.360 --> 0:13:03.080 needs convince sing as to the importance of these mental 0:13:03.120 --> 0:13:07.000 health disorders, the Global Burden of Diseases study from twenty 0:13:07.040 --> 0:13:11.120 twenty two, which importantly includes data only up till twenty 0:13:11.200 --> 0:13:14.960 nineteen and does not include the massive increase in mental 0:13:15.000 --> 0:13:19.160 health disorders worldwide that we saw due to COVID, But 0:13:19.320 --> 0:13:23.719 in twenty nineteen, depression and anxiety were top ten causes 0:13:23.800 --> 0:13:29.319 of disability adjusted life years in adolescence and adults worldwide. 0:13:30.320 --> 0:13:34.520 Self harm behaviors, which often coincide with depression, was the 0:13:34.559 --> 0:13:38.199 third leading cause of disability adjusted life years in adolescence 0:13:38.559 --> 0:13:41.520 age ten to twenty four. Yeah, gosh, And there's no 0:13:41.679 --> 0:13:45.680 evidence that these disorders are decreasing over time. If anything, 0:13:45.760 --> 0:13:50.599 they are on the rise. Anxiety disorders and depressive disorders 0:13:50.640 --> 0:13:55.720 are estimated to affect three hundred million people each worldwide, 0:13:57.360 --> 0:14:01.160 with an estimated lifetime prevalence of depression of close to 0:14:01.360 --> 0:14:04.040 twenty percent like lifetime risk. 0:14:04.280 --> 0:14:05.439 Okay. 0:14:06.160 --> 0:14:09.880 In the US in twenty twenty, nearly one in ten 0:14:10.040 --> 0:14:15.240 Americans experienced a depressive episode in the last year alone, 0:14:15.840 --> 0:14:19.640 and nearly twenty percent of adolescents and young adults experienced one. 0:14:19.960 --> 0:14:22.040 But in this study, which looked at like I think 0:14:22.080 --> 0:14:26.320 a five year period helps, seeking behavior has not been increasing, 0:14:26.920 --> 0:14:30.600 right And in a lot of studies, less than half 0:14:30.600 --> 0:14:34.080 of people with depression reported having spoken to any healthcare 0:14:34.120 --> 0:14:38.000 professional about their depression or receiving any treatment for their depression. 0:14:39.280 --> 0:14:43.080 In Europe, according to the European Psychological Association, Nearly one 0:14:43.120 --> 0:14:45.680 in five people is diagnosed with depression at some point 0:14:45.720 --> 0:14:48.080 in their lives, so that's pretty much that twenty percent 0:14:48.160 --> 0:14:53.119 lifetime prevalence, and they estimate twelve month prevalences of depression 0:14:53.200 --> 0:14:56.720 around six percent, and anxiety in the UK is estimated 0:14:56.760 --> 0:15:00.400 at around four percent, with worldwide estimates that vary from 0:15:00.400 --> 0:15:03.520 like one percent to about six percent. And like I 0:15:03.560 --> 0:15:06.640 mentioned last week, depression and anxiety often co occur, and 0:15:06.680 --> 0:15:09.560 when they do, it can be more refractory to treatment, 0:15:09.680 --> 0:15:12.960 especially when it comes to depression that like overlaps with anxiety. 0:15:13.120 --> 0:15:16.440 When they co occur, it's more challenging to treat. Just 0:15:16.640 --> 0:15:19.800 a quick question, can you and maybe you're about to 0:15:19.880 --> 0:15:24.080 do this, but define clinical definitions of anxiety depression? 0:15:24.200 --> 0:15:27.560 Yeah, It's it's hard because there are so many specific, 0:15:27.960 --> 0:15:32.840 you know, specific disorders that you can define within that, right. 0:15:33.280 --> 0:15:35.480 So maybe what about a depressive episode? 0:15:35.640 --> 0:15:38.760 Yeah, so a major depressive disorder is like would count 0:15:38.760 --> 0:15:41.480 as like one depressive episode, right, Okay, and that is 0:15:41.560 --> 0:15:46.640 usually at least two weeks of at least all of 0:15:46.720 --> 0:15:48.560 a whole bunch of different symptoms. So there's like these 0:15:48.640 --> 0:15:51.840 different checklists basically that you go through. So there has 0:15:51.880 --> 0:15:55.040 to be disruptions in sleep, which could be sleeping too 0:15:55.080 --> 0:15:59.680 little or too much. There's disruptions in your interest or 0:15:59.680 --> 0:16:02.560 like what call anhedonia, so not finding interest or pleasure 0:16:02.640 --> 0:16:05.240 in things that you used to like to do. There's 0:16:05.560 --> 0:16:07.880 energy issues, so you don't have as much energy as 0:16:07.920 --> 0:16:13.520 you used to. There's issues with concentration. There's actually feeling depressed, 0:16:13.520 --> 0:16:16.520 like having a low mood or maybe crying more easily 0:16:16.600 --> 0:16:20.320 than you used to. There's appetite issues, which could be 0:16:20.320 --> 0:16:23.840 eating more or eating less than you usually would. Sometimes 0:16:23.880 --> 0:16:27.800 we see psychomotor issues, so walking or moving very slowly 0:16:28.120 --> 0:16:30.440 or like more rapidly than you used to in the 0:16:30.440 --> 0:16:34.640 case of like anxiety for example, okay, and then there 0:16:34.720 --> 0:16:37.400 of course can be thoughts of suicide or suicidal ideation 0:16:38.520 --> 0:16:41.160 when it comes to anxiety kind of one of the 0:16:41.200 --> 0:16:44.960 biggest ones is generalized anxiety disorder, and there's separate criteria there, 0:16:44.960 --> 0:16:46.360 but a lot of it comes down to are you 0:16:46.400 --> 0:16:51.200 worrying about things like unnecessarily? Are you not able to 0:16:51.440 --> 0:16:53.840 sleep or you know, do the things that you need 0:16:53.920 --> 0:16:58.000 to because you're up all night worrying, so you're having insomnia? 0:16:58.040 --> 0:17:02.120 Are you And what's really important and that's not an 0:17:02.160 --> 0:17:05.600 exhaustive list, but there's a bunch of different questionnaires basically 0:17:05.600 --> 0:17:07.879 that you go through and you have to score certain 0:17:07.920 --> 0:17:11.800 scores in order to meet criteria. But the thing that's 0:17:11.840 --> 0:17:15.919 important about all of these, almost all of our mental 0:17:15.920 --> 0:17:19.680 health disorders, is that one of the criteria in order 0:17:19.720 --> 0:17:22.440 to diagnose them is they have to cause some kind 0:17:22.440 --> 0:17:25.240 of functional impairment, which means that the last question on 0:17:25.320 --> 0:17:29.280 any of these questionnaires, whether it's an anxiety questionnaire depression questionnaire, 0:17:29.560 --> 0:17:32.719 is how much is this How difficult is it making 0:17:33.160 --> 0:17:36.240 your life? How difficult is it making you to be 0:17:36.280 --> 0:17:39.439 able to do your work, to be able to do 0:17:39.600 --> 0:17:41.200 your home life, to be able to do the things 0:17:41.200 --> 0:17:43.840 that you need to do right? And that is the 0:17:43.920 --> 0:17:47.280 kind of like final criterion. So that's like a very 0:17:47.280 --> 0:17:50.040 brief overview of how it's not perfect with us, how 0:17:50.119 --> 0:17:52.120 we define a lot of those things. And I've got 0:17:52.119 --> 0:17:57.760 papers you could read more. Okay, okay, So full disclosure. 0:17:57.800 --> 0:18:03.440 Also because we use SSI eyes for anxiety disorders as 0:18:03.520 --> 0:18:07.679 well as depressive disorders, yea. But a lot of the 0:18:07.760 --> 0:18:11.720 data on them and a lot of the like mechanistic 0:18:11.760 --> 0:18:14.439 looking into how do they work relates to how we 0:18:14.560 --> 0:18:17.840 use SSRIs and think about them for depression. So that 0:18:18.000 --> 0:18:20.280 is most of what I'm going to talk about, but 0:18:20.359 --> 0:18:23.439 I will also mention their use in anxiety, and know 0:18:23.560 --> 0:18:25.600 that a lot of the data in terms of like 0:18:26.160 --> 0:18:28.800 is it effective or not, how much of a placebo 0:18:28.920 --> 0:18:31.399 is there or not, it's also true in anxiety the 0:18:31.520 --> 0:18:35.520 numbers might be slightly different, but I'm mostly focusing on 0:18:35.640 --> 0:18:38.400 SSRI I use in depression. They're also really important for anxiety. 0:18:38.560 --> 0:18:42.000 Okay, yeah, yeah it is, And I think that's just 0:18:42.080 --> 0:18:45.240 probably a historical artifact to some degree. Is that what's 0:18:45.320 --> 0:18:47.919 most of the studies have been focused on. And I'm 0:18:47.960 --> 0:18:53.200 sure that there's increasing like attention totally other Yeah. 0:18:53.080 --> 0:18:55.520 Well, and yeah, all of them that are kind of 0:18:55.560 --> 0:18:59.439 like approved for indications for anxiety, they had to have 0:18:59.480 --> 0:19:01.560 those studies in order to be approved for that indication. 0:19:01.640 --> 0:19:04.199 So again, the data exists, The data is there, and 0:19:04.240 --> 0:19:06.280 I have a bunch of papers that people can read 0:19:06.440 --> 0:19:07.760 to do more on it, but I had to be 0:19:07.840 --> 0:19:10.040 selective because we only have so. 0:19:10.040 --> 0:19:10.640 Much time. 0:19:12.840 --> 0:19:16.080 And so Aerin last week, you walked us through how 0:19:16.160 --> 0:19:19.800 we came up with the idea of using serotonin as 0:19:19.840 --> 0:19:23.920 a target, right in large part because we figured out 0:19:23.960 --> 0:19:26.399 I never knew it had to do with tuberculosis, but 0:19:26.920 --> 0:19:29.520 through the effects of these older what are now often 0:19:29.560 --> 0:19:35.439 called first generation antidepressants, the MAOIs and the TCAs, that 0:19:35.440 --> 0:19:38.000 that is how we've picked serotonin as a target. The 0:19:38.040 --> 0:19:42.360 beneficial effects of those types of antidepressants pointed to this 0:19:42.640 --> 0:19:47.160 monoamine hypothesis of depression. And like you told us last week, Aarin, 0:19:47.840 --> 0:19:53.280 this is not the cause of depression. Serotonin decreases in 0:19:53.359 --> 0:19:57.840 serotonin is not the cause of depression. But it has 0:19:57.960 --> 0:19:59.960 led us down the road of understanding a lot more 0:20:00.119 --> 0:20:05.240 more about depression than we used to. And because all 0:20:05.400 --> 0:20:10.000 of the different antidepressants that we use, including the kind 0:20:10.040 --> 0:20:13.560 of what are called atypical antidepressants that are not SSRIs 0:20:13.680 --> 0:20:18.360 or SNRIs, all of these, even the new fancy ones 0:20:18.359 --> 0:20:22.359 that people are very excited about, like ketamine and like zilocybin, 0:20:23.119 --> 0:20:26.560 all of these, to some extent or another, do in 0:20:26.680 --> 0:20:34.000 fact modulate some of our monoamine neurotransmitters serotonin, yes, also 0:20:34.080 --> 0:20:39.160 nor epinephrine and dopamine. Okay, So clearly there is something 0:20:40.000 --> 0:20:44.119 to the fact that these monoamines are involved in depression 0:20:44.200 --> 0:20:48.159 and anxiety and modulating these to one degree or another 0:20:48.480 --> 0:20:51.840 can help reduce the symptoms of depression and anxiety, even 0:20:51.880 --> 0:20:55.720 if we don't quite understand why or how. So to 0:20:55.760 --> 0:20:59.879 do a quick recap on what serotonin is so that 0:21:00.040 --> 0:21:03.600 you know how it's working in our bodies, I'm gonna 0:21:03.640 --> 0:21:05.560 actually take a quick step back and just talk about 0:21:05.600 --> 0:21:08.679 the idea of a neurotransmitter because I want to be 0:21:08.680 --> 0:21:13.639 able to explain what they're doing in our brains. Yeah, okay, 0:21:14.760 --> 0:21:17.240 And we've talked a lot about neurotransmitters on this podcast, 0:21:17.280 --> 0:21:19.560 like I've said the word a lot. But let me 0:21:19.640 --> 0:21:22.240 recap what these really are. These are compounds. These are 0:21:22.320 --> 0:21:25.080 chemicals that we make in a bunch of different parts 0:21:25.080 --> 0:21:27.600 of our brain and throughout our body. Serotonin, like ninety 0:21:27.640 --> 0:21:29.960 percent of our serotonin we actually produce in our gut, 0:21:30.160 --> 0:21:32.280 in neuroendocrine cells in our GI tract. 0:21:32.560 --> 0:21:34.919 What the heck amazing, I know, right. 0:21:35.280 --> 0:21:40.720 But so, neurotransmitters broadly are these chemicals that help to 0:21:40.920 --> 0:21:45.560 translate electrical signals in our brain and our peripheral nervous 0:21:45.600 --> 0:21:50.680 system into chemical signals that then cross what is called 0:21:50.720 --> 0:21:55.119 the sinnaps either between two neurons because there's a gap 0:21:55.160 --> 0:21:57.679 at the end of a neuron before it touches another neuron. 0:21:57.840 --> 0:22:01.439 There's a gap called a synapse or between a neuron 0:22:01.600 --> 0:22:04.280 and say a muscle, right where it's going to have 0:22:04.320 --> 0:22:09.720 an effect, and signals are passed in our neurons and 0:22:09.800 --> 0:22:14.240 in our brain with electricity essentially, And when these signals 0:22:14.240 --> 0:22:16.040 get to the end of a neuron, in order to 0:22:16.080 --> 0:22:19.679 cross that gap, that synapse and send the message onwards, 0:22:20.080 --> 0:22:24.640 these electric signals have to be transmitted via chemicals. Chemicals 0:22:24.640 --> 0:22:28.320 are released, they cross that gap, bind to receptors on 0:22:28.359 --> 0:22:32.520 the other side, and whatever neurotransmitter is released and whatever 0:22:32.600 --> 0:22:35.959 receptor it binds to sends whatever message it is that 0:22:35.960 --> 0:22:38.600 we're trying to send. Is that right? Generalized enough? 0:22:38.840 --> 0:22:42.280 But you gotta have somebody throwing the baseball and someone 0:22:42.359 --> 0:22:43.040 catching it. 0:22:43.080 --> 0:22:46.760 Exactly aarin, whay did you go with the baseball? Metaphors 0:22:48.320 --> 0:22:53.080 hitting it out of the park, Let them go on. So, 0:22:53.400 --> 0:22:57.320 serotonin happens to be a neurotransmitter that is involved in 0:22:57.560 --> 0:22:59.919 so many parts of our brain. 0:23:00.600 --> 0:23:03.640 Yeah, and our whole body, our whole bodies. 0:23:03.480 --> 0:23:06.960 But in our brain specifically, it helps to regulate things 0:23:07.200 --> 0:23:12.760 like mood, like sleep like, sexual activity, appetite, cognitive function, okay, 0:23:13.640 --> 0:23:18.359 And in our peripheral nervous system, it does so many 0:23:18.480 --> 0:23:21.640 other things that regulates our gut motility, our visceral sensitivity. 0:23:21.920 --> 0:23:24.760 It is part of this gut brain axis that someday 0:23:24.760 --> 0:23:27.200 we will have to do. It's also taken up by 0:23:27.200 --> 0:23:29.239 our platelets, which is why I got so excited when 0:23:29.280 --> 0:23:32.960 you said they saw this clotty stuff. Yeah, serotonin is 0:23:32.960 --> 0:23:38.400 involved in our clotting cascade. What so, serotonin is truly everywhere. 0:23:39.600 --> 0:23:46.560 Selective serotonin reuptake inhibitors or SSRIs are drugs that bind 0:23:46.880 --> 0:23:53.119 to a transporter protein on the presynaptic side. That is 0:23:53.240 --> 0:23:58.360 where we are releasing serotonin from on our nerve cells 0:23:59.320 --> 0:24:04.960 on our neuron, and this transporter's job is usually to 0:24:05.280 --> 0:24:11.720 collect the serotonin after it's been released. The catcher, the catcher, exactly. Wow, 0:24:11.720 --> 0:24:13.760 we're gonna keep going the baseball analogy. 0:24:13.880 --> 0:24:14.879 We really don't have to. 0:24:15.119 --> 0:24:15.800 No, I like it. 0:24:15.880 --> 0:24:16.920 The goalie like. 0:24:16.880 --> 0:24:18.439 What, I don't catcher. 0:24:18.440 --> 0:24:20.720 You can only think of sports related things right now 0:24:20.760 --> 0:24:21.479 for some reason. 0:24:22.840 --> 0:24:26.000 And the catcher is taking all of these serotonin balls 0:24:26.080 --> 0:24:30.200 and putting them back. Maybe it's really like the ball boy. Honestly, Okay, okakay, 0:24:30.480 --> 0:24:33.760