WEBVTT - Ep 182 SSRIs Part 1: Origin

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<v Speaker 1>My name is Will and my experience with ssriyes and

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<v Speaker 1>esenriyes started when I was in pharmacy school. Actually, I

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<v Speaker 1>was diagnosed with both anxiety and depression at the same time,

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<v Speaker 1>which was a lot of fun, especially when I was

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<v Speaker 1>in a doctorate program and my doctor started me on

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<v Speaker 1>s a telegram on lexaprob. It worked fairly well for

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<v Speaker 1>a while, needed a little bit of help from buse

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<v Speaker 1>Peronne to get through the anxiety, but I did okay.

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<v Speaker 1>That said, I still had some breakthrough symptoms and I

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<v Speaker 1>especially had side effects. I had a lot of the

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<v Speaker 1>sexual dysfunction side effects, and I also gained about thirty pounds,

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<v Speaker 1>so I swapped off of that for a while when

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<v Speaker 1>I'm a little bit of a vacation, but then my

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<v Speaker 1>symptoms started coming back and getting worse. So I got

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<v Speaker 1>started on wellbutrin bupropion, and I did a lot better

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<v Speaker 1>symptom wise on it, but again I had really really

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<v Speaker 1>bad side effects. And it wasn't so much suicidal ideation

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<v Speaker 1>as it was just an acute knowledge of my own mortality,

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<v Speaker 1>which is not great when you had anxiety and depression.

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<v Speaker 1>So at that point I had the wherewithal because of

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<v Speaker 1>my education as a pharmacist to ask my doctor to

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<v Speaker 1>go on and do genetic testing, which I'm glad I

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<v Speaker 1>did because when we got the results back, it turned

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<v Speaker 1>out that there were only about two antidepressants and a

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<v Speaker 1>couple of anxiolytics that were on my green as go list.

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<v Speaker 1>That is to say, you know that my hepatic enzyme

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<v Speaker 1>is going to metabolize without giving me two bad side effects.

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<v Speaker 1>And that is kind of the journey of how I

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<v Speaker 1>found pristique des been the fact sine that is the

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<v Speaker 1>miracle drug that worked for me. But I still can't

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<v Speaker 1>help but wonder how long it would have taken me

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<v Speaker 1>to find my miracle drug if we did it kind

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<v Speaker 1>of the old fashioned way. If I hadn't known to

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<v Speaker 1>ask for this genetic testing, I could have been trying

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<v Speaker 1>and failing SSRIs and SNRIs for years, years before I

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<v Speaker 1>found the drug that worked for me. So you know,

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<v Speaker 1>I try and advocate for the genetic testing and for

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<v Speaker 1>being your own advocate as a patient whenever I can,

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<v Speaker 1>because I just I know that there are a ton

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<v Speaker 1>of people that don't have the same sort of background

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<v Speaker 1>as I had the good fortune of having. So as

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<v Speaker 1>a fellow health professional, I definitely tell patients all the time,

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<v Speaker 1>make sure you're advocating for yourself, even if it's just

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<v Speaker 1>asking questions.

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<v Speaker 2>Taking SSRIs is the best thing I've ever done. I've

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<v Speaker 2>always had trouble with OCD in terminal anxiety from a

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<v Speaker 2>young age, probably as long as I can remember. I

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<v Speaker 2>would have like a baseline level of anxiety and OCD,

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<v Speaker 2>and then every so often I'd have these periods where

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<v Speaker 2>it got so much worse and it was all consuming.

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<v Speaker 2>I spent all my time in my own head, worrying, ruminate,

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<v Speaker 2>in doom, mental compulsions. I struggled to eat, or sleep

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<v Speaker 2>or socialize, and it really started to have an effect

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<v Speaker 2>on my personal life. I managed to get through work

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<v Speaker 2>and other commitments without most people noticing, but I wasn't

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<v Speaker 2>present and it was really horrible to endure. I felt

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<v Speaker 2>like I didn't deserve anything nice or for my family

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<v Speaker 2>to be even sympathetic to me because of these awful,

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<v Speaker 2>intrusive thoughts I was having. These periods were so difficult

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<v Speaker 2>that when they subsided, I was so grateful that I

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<v Speaker 2>didn't even notice the baseline level of anxiety I had

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<v Speaker 2>all the time, and how much of an impact that

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<v Speaker 2>was having on my life. Last October, I had an

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<v Speaker 2>OCD flare up, and it was the worst it's ever been.

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<v Speaker 2>I was in a really dark place. My therapist recommended

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<v Speaker 2>taking fla woxatine, and I was so desperate to feel

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<v Speaker 2>better I would have taken anything. Within a few weeks,

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<v Speaker 2>I started to feel more myself again. The thoughts quietened,

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<v Speaker 2>and I remember getting really emotional because it was so

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<v Speaker 2>strange for me to feel like that, my mind being

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<v Speaker 2>quiet for once. I can't emphasize enough how much of

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<v Speaker 2>a sitive impact they've had on my life. It was

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<v Speaker 2>the first time in my life I'd actually felt content

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<v Speaker 2>in myself and excited for the future. I'm so much

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<v Speaker 2>happier now and just enjoying life to the fun. I'm

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<v Speaker 2>so grateful that I don't have to feel that permanent

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<v Speaker 2>level of anxiety and intrusive thoughts anymore.

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<v Speaker 3>I've literally never felt.

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<v Speaker 2>Like this in my life before, and it really hammered

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<v Speaker 2>home how much I'd been struggling on a daily basis

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<v Speaker 2>and didn't even notice. The tablets alongside the therapy were

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<v Speaker 2>like a helping hand to pull me out of a

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<v Speaker 2>really dark hole. My only regret is not taking them.

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<v Speaker 2>Any sooner.

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<v Speaker 4>Thank you so much for providing your first hand account.

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<v Speaker 4>That really means it means so much. I know we

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<v Speaker 4>say it all the time, but it always does. It

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<v Speaker 4>really does.

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<v Speaker 5>It means so much every single time, honestly, So thank you,

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<v Speaker 5>and thank you to everyone who wrote in. We really

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<v Speaker 5>really do appreciate it.

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<v Speaker 3>We do.

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<v Speaker 5>Hi.

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<v Speaker 3>I'm Aaron Welsh.

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<v Speaker 5>And I'm Erin Alman Updike and this is this podcast

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<v Speaker 5>will kill You. And today we're talking about SSRIs.

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<v Speaker 4>About SSRIs, and next week we're talking about SSRSR. Yeah,

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<v Speaker 4>I mean, it really does warrant at least two full episodes,

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<v Speaker 4>Like there's so much there in the history, in the

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<v Speaker 4>biology and sort of the current the discourse.

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<v Speaker 3>James, we did not plan that, No, we did. That's thrilling.

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<v Speaker 3>Just shows that we're best friends.

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<v Speaker 5>Like yeah, and we spent way too much time like

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<v Speaker 5>thinking about this too and with each other.

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<v Speaker 3>Yeah yeah, yeah.

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<v Speaker 5>But yeah, So we're gonna do a two parter this week.

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<v Speaker 5>Aaron Welsh's gonna tell me all about the history because

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<v Speaker 5>I don't know it other than like we had MAOIs

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<v Speaker 5>and then TCAs and now SSRI's what I've done. Next

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<v Speaker 5>episode and then next week, I'll get into what we

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<v Speaker 5>think we know about how SSRIs actually work and their mechanism,

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<v Speaker 5>and then yeah, I'm excited to tell you what I know,

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<v Speaker 5>and then some of the yeah, the current discourse.

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<v Speaker 3>Current.

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<v Speaker 4>But before we get into all all of that, it

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<v Speaker 4>is of course quarantine.

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<v Speaker 5>Quarantin any time or should we say plusy berrita time.

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<v Speaker 4>This week we've been like mixing it up and every

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<v Speaker 4>now and then it's like, what do you what do

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<v Speaker 4>you feel like doing plasy parita This week we'll do

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<v Speaker 4>this one. Yeah, this week is the serotonin sprits.

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<v Speaker 5>Couldn't be anything else. It could have been Actually we

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<v Speaker 5>thought about other things.

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<v Speaker 4>We were like, this is as bad as it is.

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<v Speaker 4>It's the best we can do.

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<v Speaker 3>Saraton sprits. It's pretty simple.

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<v Speaker 4>It's it's got soda water, hence the sprits. It's got

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<v Speaker 4>sparkling apple cider and some pineapple juice. And it's tasty.

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<v Speaker 4>It's simple, it's refreshing.

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<v Speaker 5>Yeah, for a warm or a cold day.

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<v Speaker 4>Yeah, sure, jack of all trades anyway.

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<v Speaker 5>The full recipe on our website, this podcast with kill

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<v Speaker 5>you dot com and our socials. Are you following us there?

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<v Speaker 5>Because you could and should be. We're on Instagram, TikTok,

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<v Speaker 5>the Facebook, loose Sky. We're also online on a website

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<v Speaker 5>called This Podcast Will Kill You dot com. Have you

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<v Speaker 5>checked it out yet, because if you haven't, what a

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<v Speaker 5>wealth of things you'll find there.

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<v Speaker 3>So many things.

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<v Speaker 5>The bookshop dot org affiliate list account that we have.

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<v Speaker 5>You're doing you're doing it, thank you, good reads list, transcripts,

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<v Speaker 5>We've got Bloodmobile. We've got sources from every single one

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<v Speaker 5>of our episodes, including this one.

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<v Speaker 3>What else is now on Instagram?

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<v Speaker 5>So oh really that's exciting.

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<v Speaker 3>Check them out.

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<v Speaker 5>Check we've got merch We've got a link to our

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<v Speaker 5>Patreon account. If you haven't yet dropped a what do

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<v Speaker 5>you call it? Rate and review and subscribe. I'm trying

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<v Speaker 5>to do too much.

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<v Speaker 3>Be sure to do that. Do it?

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<v Speaker 5>Okay, we're on YouTube.

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<v Speaker 1>There we go.

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<v Speaker 3>Let's just try to take a little off your plate.

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<v Speaker 3>Thank you.

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<v Speaker 5>My plate is done.

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<v Speaker 4>The end, the end, and the beginning. Let's take a

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<v Speaker 4>quick break and get started.

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<v Speaker 5>I can't wait.

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<v Speaker 4>In December nineteen eighty seven, the FDA approved Prozac for

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<v Speaker 4>treatment of depression, and it became the first ssri to

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<v Speaker 4>hit the US market. The following January within two years,

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<v Speaker 4>pharmacies were filing one million prescriptions each month.

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<v Speaker 5>Wow in the US.

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<v Speaker 3>In the US Wow.

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<v Speaker 4>Today, global numbers are hard to pin down. I'm sure

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<v Speaker 4>you'll do some Aaron math maybe, but no, I won't. Sorry, well,

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<v Speaker 4>they're really hard to find. I mean, googled for like

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<v Speaker 4>five minutes and no, it was longer than that.

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<v Speaker 5>Was I believe it was substantially longer than that.

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<v Speaker 4>But I did find one estimate from the CDC from

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<v Speaker 4>twenty eighteen where they suggested that thirteen percent of people

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<v Speaker 4>in the US are on antidepressants, which comes out to

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<v Speaker 4>around forty two million people, and this is likely an

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<v Speaker 4>underestimate since prescriptions have increased in recent years. As antidepressant

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<v Speaker 4>use has grown, so has the controversy surrounding these medications.

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<v Speaker 4>RFK Junior, the Secretary of the US Department of Health

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<v Speaker 4>and Human Services, despite having zero medical training, has made

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<v Speaker 4>claims that SSRIs are more harmful and addictive than heroin,

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<v Speaker 4>so claims not supported by any data, and has proposed

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<v Speaker 4>limiting their use, instead sending people to quote unquote wellness farms. Yeah,

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<v Speaker 4>I mean we could do an entire Yeah.

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<v Speaker 5>I'm sorry, it's just so unseerious, but it's very very serious.

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<v Speaker 5>He's very much in charge of everything right now. But

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<v Speaker 5>it's one of those you laugh or you just break

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<v Speaker 5>down and give up on everything.

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<v Speaker 3>Is I laugh?

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<v Speaker 4>I mean I'm scared every day and it feels surreal

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<v Speaker 4>every day.

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<v Speaker 5>And yeah, yep, I mean.

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<v Speaker 3>This is like.

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<v Speaker 4>Wellness farms are not a new concept, and it's never

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<v Speaker 4>been a good concept. We could do an entire episode

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<v Speaker 4>in the dark history of wellness farms or the ones

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<v Speaker 4>similar to the ones that he presumably has in mind,

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<v Speaker 4>my guess, and how ablest and racist and sexist and

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<v Speaker 4>classist they are.

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<v Speaker 5>It's dark. It's dark.

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<v Speaker 3>It's dark.

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<v Speaker 4>But this controversy extends beyond conspiracy theories and conspiracy theorists

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<v Speaker 4>like RFK Junior, with some psychiatrists and researchers expressing reservations

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<v Speaker 4>about the way that we use or think about antidepressants

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<v Speaker 4>and mental health disorders, prompting the popular media to release

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<v Speaker 4>articles exploring this controversy with headlines like the risks and

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<v Speaker 4>Rewards of antidepressants and do antidepressants work better than Placebo?

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<v Speaker 3>Despite all the.

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<v Speaker 4>Progress that has been made in raising awareness and being

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<v Speaker 4>open about mental illness, it is still a taboo subject

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<v Speaker 4>in many ways, very much so. Acknowledging that you struggle

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<v Speaker 4>and seeking help because of that is perceived by some

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<v Speaker 4>as or by many, as a weakness.

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<v Speaker 3>Oh we all.

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<v Speaker 4>Get a little blue here and there. You don't need meds.

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<v Speaker 4>Just think on the bright side, go get some fresh air,

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<v Speaker 4>just take a walk, take a nice little stroll. Or yeah,

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<v Speaker 4>I get anxious too. Sometimes I just try not to

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<v Speaker 4>think about it.

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<v Speaker 3>Just kind of put it in a box, put it away.

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<v Speaker 3>Just stop.

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<v Speaker 5>Yeah, just stop to stop. Just stop being anxious and depressed.

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<v Speaker 3>That's easy, that's easy.

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<v Speaker 4>The stigma surrounding mental health disorders also extends to the

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<v Speaker 4>treatments that people seek, whether that's an SSRI or therapy,

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<v Speaker 4>and the stigma, no doubt, contributes to the constant questioning

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<v Speaker 4>of antidepressants by the general public. However, the skepticism that

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<v Speaker 4>some researchers or healthcare practitioners express towards SSRIs, while likely

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<v Speaker 4>influenced by this overarching doubt, is also informed by the

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<v Speaker 4>gaps in our scientific knowledge about the causes of mental

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<v Speaker 4>illness and the mechanisms by which SSRIs may work to

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<v Speaker 4>improve symptoms. So, in other words, like what do these

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<v Speaker 4>medications do and how do they do it? And next week, Aaron,

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<v Speaker 4>I know that you're going to take us through the

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<v Speaker 4>long answers to these questions, but the short answer is

0:13:50.920 --> 0:13:52.640
<v Speaker 4>that we don't really know.

0:13:53.200 --> 0:13:56.160
<v Speaker 5>Yeah, I mean, that's the conclusion of next week's episode.

0:13:56.320 --> 0:13:59.640
<v Speaker 4>Yeah, yeah, yeah, I mean we have some ideas, and

0:14:00.080 --> 0:14:03.120
<v Speaker 4>those ideas have changed over the decades, but we don't

0:14:03.160 --> 0:14:07.240
<v Speaker 4>know for certain how these medications work. And that's partly

0:14:07.280 --> 0:14:11.719
<v Speaker 4>because we don't understand the underpinnings of depression, of anxiety,

0:14:11.840 --> 0:14:16.959
<v Speaker 4>of obsessive compulsive disorder, and of other mental health disorders. Yeah,

0:14:17.000 --> 0:14:20.360
<v Speaker 4>and at first glance that maybe that sounds a little strange,

0:14:20.400 --> 0:14:23.360
<v Speaker 4>like what do you mean we use these antidepressants but

0:14:23.400 --> 0:14:25.080
<v Speaker 4>we don't quite know how they work.

0:14:26.040 --> 0:14:27.800
<v Speaker 5>It doesn't sound strange if you work in medicine.

0:14:27.800 --> 0:14:30.520
<v Speaker 4>Aaron I was gonna say, there are still there's so

0:14:30.640 --> 0:14:35.080
<v Speaker 4>many medications that are also mysterious. There's acetaminifin paracetamol. We

0:14:35.120 --> 0:14:37.520
<v Speaker 4>don't know why or how it reduces pain and fever.

0:14:37.960 --> 0:14:40.440
<v Speaker 4>Met Foreman is still a bit of a black box.

0:14:40.560 --> 0:14:43.640
<v Speaker 4>Even a few of our general anesthetics holds some mystery.

0:14:43.840 --> 0:14:47.600
<v Speaker 5>There is probably more medicines that we do not fully understand.

0:14:48.160 --> 0:14:50.080
<v Speaker 5>And I don't just mean like how they work, like

0:14:50.680 --> 0:14:52.360
<v Speaker 5>a lot of things we know, like it binds to

0:14:52.440 --> 0:14:56.040
<v Speaker 5>this receptor and this mechanism happens. That does not mean

0:14:56.040 --> 0:14:59.800
<v Speaker 5>that we understand how like why do they improve the

0:14:59.840 --> 0:15:01.880
<v Speaker 5>thing that they improve, because we use a lot of

0:15:01.920 --> 0:15:05.720
<v Speaker 5>medicines for a whole bunch of different stuff, Like I'm

0:15:05.720 --> 0:15:08.720
<v Speaker 5>going to get into it next week more as well too,

0:15:08.880 --> 0:15:11.120
<v Speaker 5>like this concept and the way that we talk about

0:15:11.240 --> 0:15:15.000
<v Speaker 5>these medicines for depression versus other medicines that we don't understand.

0:15:15.440 --> 0:15:18.760
<v Speaker 5>But yeah, it's it is not just SSRIs.

0:15:18.120 --> 0:15:19.160
<v Speaker 3>It's not it's not.

0:15:19.800 --> 0:15:23.480
<v Speaker 4>And I think that this speaks to how our approach

0:15:23.600 --> 0:15:26.920
<v Speaker 4>to drug development is not always guided by a find

0:15:26.960 --> 0:15:31.320
<v Speaker 4>the specific problem, engineer the targeted solution mindset, Like that's

0:15:31.480 --> 0:15:34.160
<v Speaker 4>just not the way that drug development often works, and

0:15:34.200 --> 0:15:38.040
<v Speaker 4>maybe maybe that's the ideal way, but like that rarely

0:15:38.160 --> 0:15:41.600
<v Speaker 4>rarely happens, or it doesn't happen, and we think that

0:15:41.680 --> 0:15:43.880
<v Speaker 4>we've found the solution, but it's like, well, we didn't

0:15:43.960 --> 0:15:45.880
<v Speaker 4>quite understand the problem in the first place.

0:15:46.200 --> 0:15:48.560
<v Speaker 5>That's the thing. You have to know the problem very

0:15:48.600 --> 0:15:51.080
<v Speaker 5>clearly to be able to do that kind of targeted development.

0:15:51.120 --> 0:15:55.359
<v Speaker 5>So we have that for some situations, right, for some cancers,

0:15:55.400 --> 0:15:59.400
<v Speaker 5>for example, Yes, but not for a lot of other

0:15:59.600 --> 0:16:03.320
<v Speaker 5>disorder that are more nebulous, that have multiple factors that

0:16:03.400 --> 0:16:05.280
<v Speaker 5>contribute to their development. Right.

0:16:05.720 --> 0:16:08.280
<v Speaker 4>I mean it's kind of it's kind of amazing, like

0:16:09.040 --> 0:16:14.280
<v Speaker 4>and just just how much serendipity can play a huge

0:16:14.440 --> 0:16:18.800
<v Speaker 4>role in bridging these gaps of like, we here's this problem.

0:16:18.840 --> 0:16:20.280
<v Speaker 3>What's the solution? Right?

0:16:20.320 --> 0:16:24.480
<v Speaker 4>We don't have the information, But then something comes along

0:16:24.520 --> 0:16:26.120
<v Speaker 4>and it's like, hey, that seems to work.

0:16:26.600 --> 0:16:28.960
<v Speaker 5>How does it work? How does We'll figure that out

0:16:29.040 --> 0:16:33.480
<v Speaker 5>later right now? Yeah, it's what is it doing first?

0:16:33.520 --> 0:16:35.640
<v Speaker 5>And then how does it work? How does it We

0:16:35.680 --> 0:16:37.080
<v Speaker 5>don't have the how does it work for a lot

0:16:37.080 --> 0:16:37.440
<v Speaker 5>of things?

0:16:37.560 --> 0:16:38.760
<v Speaker 3>Yes? Yeah?

0:16:38.800 --> 0:16:40.680
<v Speaker 4>And so what I want to do in this episode

0:16:40.760 --> 0:16:44.160
<v Speaker 4>is take us through the story of SSRIs, starting with

0:16:44.280 --> 0:16:48.240
<v Speaker 4>serotonin itself and how the first antidepressants were developed, and

0:16:48.240 --> 0:16:52.000
<v Speaker 4>then ultimately ending with kind of a small reflection of

0:16:52.040 --> 0:16:56.200
<v Speaker 4>how these medications have led a revolution in our understanding

0:16:56.240 --> 0:16:59.840
<v Speaker 4>and perception of mental illness. That's the good, the bad,

0:17:00.000 --> 0:17:01.560
<v Speaker 4>and everything in between.

0:17:01.920 --> 0:17:02.440
<v Speaker 5>I can't wait.

0:17:02.520 --> 0:17:07.400
<v Speaker 4>So let's start at the beginning with serotonin. The neurotransmitter

0:17:07.520 --> 0:17:10.919
<v Speaker 4>and cellular messenger. That's the star of this episode.

0:17:11.040 --> 0:17:11.760
<v Speaker 5>I can't wait.

0:17:13.359 --> 0:17:14.920
<v Speaker 3>Which to do.

0:17:15.040 --> 0:17:19.000
<v Speaker 4>This means that we have to start pretty far back, Okay,

0:17:19.240 --> 0:17:21.200
<v Speaker 4>billions of years back.

0:17:21.440 --> 0:17:21.600
<v Speaker 3>You know.

0:17:21.680 --> 0:17:23.520
<v Speaker 5>I love it when you go deep time a time.

0:17:23.760 --> 0:17:26.080
<v Speaker 4>I mean, I'm not going to stay deep for very long,

0:17:26.160 --> 0:17:27.560
<v Speaker 4>but it's okay, it is.

0:17:28.200 --> 0:17:28.840
<v Speaker 3>I was so.

0:17:28.720 --> 0:17:34.160
<v Speaker 4>Surprised to learn how ancient serotonin serotonin, I mean two

0:17:34.200 --> 0:17:36.200
<v Speaker 4>to three billion years ago.

0:17:37.000 --> 0:17:37.320
<v Speaker 5>Wow.

0:17:37.440 --> 0:17:40.359
<v Speaker 4>It can basically be found in all walks of life,

0:17:40.359 --> 0:17:45.160
<v Speaker 4>from bacteria to protozoans, leeches, worms, fishes, birds, plants. Did

0:17:45.200 --> 0:17:46.800
<v Speaker 4>you know that plants make serotonin?

0:17:47.200 --> 0:17:49.040
<v Speaker 5>No? But that makes me so happy.

0:17:49.119 --> 0:17:52.920
<v Speaker 3>I know why I don't know dogs humans?

0:17:53.000 --> 0:17:56.480
<v Speaker 4>I mean basically yeah, I mean dogs make sense. Plants

0:17:56.560 --> 0:18:00.040
<v Speaker 4>is a little more like it's a little what so

0:18:00.200 --> 0:18:04.480
<v Speaker 4>basically everything. It exists in all the organs of the

0:18:04.560 --> 0:18:08.399
<v Speaker 4>human body, which is pretty fascinating, but not as fascinating

0:18:08.440 --> 0:18:10.920
<v Speaker 4>as the fact that it's found in basically every living

0:18:11.000 --> 0:18:12.320
<v Speaker 4>organism on this planet.

0:18:12.600 --> 0:18:14.880
<v Speaker 3>Wow, So what does this tell us?

0:18:15.240 --> 0:18:19.520
<v Speaker 4>Like, it's so widespread and so ancient that it means

0:18:19.560 --> 0:18:23.640
<v Speaker 4>that a this serotonin is got to be really important,

0:18:23.880 --> 0:18:28.600
<v Speaker 4>super important, and be just how many ways. It is important,

0:18:28.640 --> 0:18:30.600
<v Speaker 4>like the varied roles that it can play.

0:18:30.680 --> 0:18:33.240
<v Speaker 5>It's obviously not just doing one thing exactly.

0:18:33.320 --> 0:18:37.879
<v Speaker 4>It's not just oh, this is the depression neurotransmitter in

0:18:38.040 --> 0:18:42.000
<v Speaker 4>humans only, right, Yeah, I mean, and we tend to

0:18:42.119 --> 0:18:45.640
<v Speaker 4>think of and describe serotonin as a neurotransmitter, which it is,

0:18:45.680 --> 0:18:49.280
<v Speaker 4>but it also existed before neurons did.

0:18:49.119 --> 0:18:51.320
<v Speaker 5>Oh my gosh, stop.

0:18:51.160 --> 0:18:52.400
<v Speaker 3>Isn't that wild?

0:18:52.520 --> 0:18:55.840
<v Speaker 5>Well, yeah, because if you're talking about bacteria have serotonin,

0:18:55.960 --> 0:19:00.480
<v Speaker 5>I didn't know that. Yeah, yeah, you don't have neurons exactly,

0:19:00.520 --> 0:19:01.879
<v Speaker 5>You're just one cell.

0:19:02.080 --> 0:19:05.920
<v Speaker 4>This neurotransmitter existed before it could be transmitted by neurons.

0:19:06.000 --> 0:19:09.800
<v Speaker 3>Like, what is so cool? It's so cool?

0:19:10.520 --> 0:19:12.679
<v Speaker 5>Do we know what that does in bacteria?

0:19:13.280 --> 0:19:16.600
<v Speaker 4>I'm watching a lot of it is like energy capture

0:19:16.760 --> 0:19:21.560
<v Speaker 4>or regulation or management. Sometimes there's like intracellular or like

0:19:22.080 --> 0:19:23.600
<v Speaker 4>a signaling between.

0:19:23.240 --> 0:19:28.480
<v Speaker 5>Different still signal what it is for us? Okay, okay, yeah, yeah.

0:19:28.560 --> 0:19:29.760
<v Speaker 3>I mean it is involved.

0:19:29.760 --> 0:19:31.280
<v Speaker 4>Like these are just some of the things that it's

0:19:31.320 --> 0:19:36.119
<v Speaker 4>involved in just across life, which is regulating cell activity

0:19:36.160 --> 0:19:41.080
<v Speaker 4>and signaling. Development and plasticity plays a huge role generation,

0:19:42.200 --> 0:19:49.680
<v Speaker 4>energy consumption, metamorphosis, embryogenesis, digestion, feeding behaviors, motor activities, sleep regulation,

0:19:49.800 --> 0:19:55.639
<v Speaker 4>neurological development, decision making, stress responses, mood behavior, social dynamics, anxiety, learning,

0:19:56.000 --> 0:19:58.680
<v Speaker 4>and memory, just to name a few, just a few.

0:20:00.119 --> 0:20:04.000
<v Speaker 4>It's everywhere does everything. Yeah, and so Aarin, I know

0:20:04.040 --> 0:20:07.280
<v Speaker 4>that next week you'll tell us more about what seratonin's

0:20:07.320 --> 0:20:09.480
<v Speaker 4>role is thought to be in humans, or like at

0:20:09.520 --> 0:20:12.120
<v Speaker 4>least some of the things that we know it does, right,

0:20:12.240 --> 0:20:14.000
<v Speaker 4>But I wanted to share just a couple of fun

0:20:14.040 --> 0:20:16.920
<v Speaker 4>tidbits that I discovered in researching for this. I can't

0:20:17.040 --> 0:20:20.080
<v Speaker 4>not on the non human side of things. Okay, So

0:20:20.160 --> 0:20:23.399
<v Speaker 4>we love leeches, we do, and we.

0:20:24.840 --> 0:20:25.720
<v Speaker 3>Love kissing bugs.

0:20:25.800 --> 0:20:27.880
<v Speaker 4>Is love is not the right word, But we are

0:20:27.920 --> 0:20:29.439
<v Speaker 4>intrigued by kissing gigs.

0:20:29.840 --> 0:20:32.159
<v Speaker 5>Appreciate their They are interesting.

0:20:31.680 --> 0:20:35.000
<v Speaker 4>Creatures, yes, and we have episodes that feature both of

0:20:35.040 --> 0:20:40.479
<v Speaker 4>these creatures. In these two In medicinal leeches and kissing bugs,

0:20:40.560 --> 0:20:43.960
<v Speaker 4>serotonin acts as a signal to expand their stomach so

0:20:44.000 --> 0:20:46.320
<v Speaker 4>that they can eat many, many, many more times their

0:20:46.359 --> 0:20:47.720
<v Speaker 4>body size blood.

0:20:47.720 --> 0:20:50.560
<v Speaker 5>It's what, lets just suck all of our blood.

0:20:50.359 --> 0:20:53.000
<v Speaker 4>Yep yep, just expand expand. It also seems to help

0:20:53.440 --> 0:20:54.640
<v Speaker 4>leeches swim.

0:20:55.040 --> 0:20:55.960
<v Speaker 5>Oh.

0:20:56.119 --> 0:21:00.160
<v Speaker 4>In some species of worms, it stimulates development and egg laying.

0:21:01.240 --> 0:21:06.040
<v Speaker 4>In certain marine molluscs, environmental serotonin is needed to induce

0:21:06.240 --> 0:21:09.560
<v Speaker 4>metamorphosis from the larval to the adult stage, and so

0:21:09.720 --> 0:21:13.320
<v Speaker 4>it's thought that the serotonin is produced by algae which

0:21:13.359 --> 0:21:17.200
<v Speaker 4>the mollusks feed on. And so if you are detecting

0:21:17.280 --> 0:21:20.160
<v Speaker 4>not high enough levels of serotonin and you're a mollusk

0:21:20.280 --> 0:21:22.800
<v Speaker 4>and you're like, wait, where's the serotonin the environment and

0:21:22.840 --> 0:21:25.919
<v Speaker 4>it's a little low, that could signal a resource poor area.

0:21:26.000 --> 0:21:28.120
<v Speaker 4>So it's like, don't metamorphose here, you won't get enough

0:21:28.160 --> 0:21:31.120
<v Speaker 4>to eat. What serotonin?

0:21:31.640 --> 0:21:32.520
<v Speaker 5>Serotonin?

0:21:33.000 --> 0:21:36.840
<v Speaker 4>It's incredible, I mean, and we could spend forever talking

0:21:36.840 --> 0:21:39.960
<v Speaker 4>about what serotonin does in different species or tissues or organs.

0:21:40.000 --> 0:21:43.480
<v Speaker 4>But do you know what else is fascinating about serotonin?

0:21:43.600 --> 0:21:49.320
<v Speaker 4>I want to how it was discovered, Okay, okay. I

0:21:49.400 --> 0:21:52.760
<v Speaker 4>was surprised that how much serotonin history. I was like, okay,

0:21:52.800 --> 0:21:55.960
<v Speaker 4>I got to start at the beginning. What's the story

0:21:55.960 --> 0:21:56.720
<v Speaker 4>of serotonin?

0:21:57.040 --> 0:21:57.200
<v Speaker 5>Right?

0:21:57.280 --> 0:21:59.480
<v Speaker 4>And then I was like, actually, this is fascinating. But

0:21:59.560 --> 0:22:03.080
<v Speaker 4>I've thought about serotonin in isolation, like I've always thought

0:22:03.080 --> 0:22:06.240
<v Speaker 4>about it in the context of SSRIs or in mental

0:22:06.240 --> 0:22:08.199
<v Speaker 4>health disorders and like, what does it do in humans?

0:22:08.240 --> 0:22:13.040
<v Speaker 4>Without thinking of it? It's a broader picture. Yeah, yeah, okay,

0:22:13.119 --> 0:22:17.960
<v Speaker 4>So serotonin discovery. The early decades of the twentieth century

0:22:18.720 --> 0:22:23.119
<v Speaker 4>were an exciting time to be a molecular biologist because

0:22:23.200 --> 0:22:27.720
<v Speaker 4>what they found was that these increasingly sensitive bioassays allowed

0:22:27.760 --> 0:22:31.119
<v Speaker 4>them to tease apart the functions of the tiny compounds

0:22:31.119 --> 0:22:35.080
<v Speaker 4>that are constantly flitting around within the bodies of animals,

0:22:35.119 --> 0:22:41.200
<v Speaker 4>humans and other animals, things like hormones or antibodies, vitamins,

0:22:41.400 --> 0:22:45.720
<v Speaker 4>and of course neurotransmitters. What do these different molecules do,

0:22:46.400 --> 0:22:49.560
<v Speaker 4>how do they interact with one another, what happens if

0:22:49.600 --> 0:22:53.280
<v Speaker 4>things go awry? And how can we use all this

0:22:53.400 --> 0:22:58.360
<v Speaker 4>knowledge to develop medications to treat certain conditions. These were

0:22:58.440 --> 0:23:02.040
<v Speaker 4>the types of questions that motivated many researchers in the

0:23:02.119 --> 0:23:07.080
<v Speaker 4>nineteen thirties, among them an Italian physiologist and pharmacologist named

0:23:07.200 --> 0:23:08.680
<v Speaker 4>Vittorio or Spammer.

0:23:09.280 --> 0:23:09.800
<v Speaker 3>We'll try that.

0:23:10.680 --> 0:23:12.600
<v Speaker 4>I say his name a bunch more times, so great,

0:23:13.320 --> 0:23:18.119
<v Speaker 4>but Erspimer had a particular interest in deriving pharmacologically active

0:23:18.160 --> 0:23:21.439
<v Speaker 4>substances from nature to use in medications because he so

0:23:21.480 --> 0:23:25.680
<v Speaker 4>he would be like, what is this plant alkaloid. Can

0:23:25.680 --> 0:23:27.639
<v Speaker 4>we use this as a medication? What does it do

0:23:28.320 --> 0:23:30.840
<v Speaker 4>these sorts of things? Okay, it was a very hot

0:23:30.840 --> 0:23:33.439
<v Speaker 4>time for that. If you think also of things like

0:23:33.840 --> 0:23:38.160
<v Speaker 4>willow and aspirin, and you think of quinine malaria, that's

0:23:38.160 --> 0:23:39.120
<v Speaker 4>sort of right anyway.

0:23:40.080 --> 0:23:41.119
<v Speaker 3>So his work.

0:23:41.320 --> 0:23:45.480
<v Speaker 4>Erspimer's work centered around the smooth muscle of animals and

0:23:46.000 --> 0:23:49.119
<v Speaker 4>trying to figure out which substances caused it to constrict

0:23:49.280 --> 0:23:52.840
<v Speaker 4>or contract. So he looked at the skins and intestines

0:23:52.880 --> 0:23:56.120
<v Speaker 4>of rabbits, of molluks, of molluscs it's a hard word

0:23:56.119 --> 0:24:00.119
<v Speaker 4>to say, and of frogs to name a few, and

0:24:00.280 --> 0:24:03.000
<v Speaker 4>substance found in a certain type of cells in the

0:24:03.080 --> 0:24:07.439
<v Speaker 4>gut caught his eye. When he isolated it and tested

0:24:07.480 --> 0:24:10.440
<v Speaker 4>it out. He observed that it caused smooth muscle contraction,

0:24:10.920 --> 0:24:13.200
<v Speaker 4>and it didn't seem to be any of the recently

0:24:13.240 --> 0:24:17.639
<v Speaker 4>discovered usual suspects. It was something completely undescribed at that point,

0:24:18.240 --> 0:24:21.680
<v Speaker 4>and so he named it enteramine in his nineteen thirty

0:24:21.680 --> 0:24:22.240
<v Speaker 4>seven paper.

0:24:22.960 --> 0:24:23.480
<v Speaker 5>Okay.

0:24:24.119 --> 0:24:26.879
<v Speaker 4>In the subsequent years, he found the substance in many

0:24:26.960 --> 0:24:31.919
<v Speaker 4>other organisms and tissues, mollus cart octopus, salivary glands like

0:24:32.320 --> 0:24:38.120
<v Speaker 4>I guess had a particular bent towards ocean creatures. Yeah, creatures,

0:24:38.800 --> 0:24:42.440
<v Speaker 4>and he seemed quite enamored with it. In a letter

0:24:42.480 --> 0:24:44.520
<v Speaker 4>that he wrote at eighty nine years old, so way

0:24:44.560 --> 0:24:50.720
<v Speaker 4>way later, he described it as quote unquote my firstborn daughter, Okay,

0:24:50.840 --> 0:24:52.159
<v Speaker 4>really loved enter remine.

0:24:52.240 --> 0:24:53.920
<v Speaker 3>Yeah.

0:24:53.960 --> 0:24:59.000
<v Speaker 4>But where Erstimer was actively looking for this stuff, another

0:24:59.080 --> 0:25:06.080
<v Speaker 4>research group which was comprised of researchers Maurice, Rapport, Arta Green,

0:25:06.280 --> 0:25:09.480
<v Speaker 4>and Irvine Page, they were looking for how to get

0:25:09.560 --> 0:25:12.800
<v Speaker 4>rid of it. So since nineteen forty eight they had

0:25:12.840 --> 0:25:15.960
<v Speaker 4>been investigating the cause of hypertension in the hopes of

0:25:16.000 --> 0:25:19.520
<v Speaker 4>developing a drug and kept coming across the substance in

0:25:19.560 --> 0:25:22.199
<v Speaker 4>their clotted blood samples, where it seemed to act as

0:25:22.200 --> 0:25:27.760
<v Speaker 4>a vasoconstrictor interesting erin. Yeah, and so they were like, gosh,

0:25:28.040 --> 0:25:31.440
<v Speaker 4>this is like one collaborator later said, Yeah, the group

0:25:31.560 --> 0:25:33.760
<v Speaker 4>just kind of thought of it as a contaminant, and

0:25:33.800 --> 0:25:36.000
<v Speaker 4>they were like, how can we identify this so that

0:25:36.040 --> 0:25:37.639
<v Speaker 4>we can get rid of it, get rid of it

0:25:37.680 --> 0:25:40.199
<v Speaker 4>out of our samples, I mean, And that might be

0:25:40.320 --> 0:25:45.160
<v Speaker 4>underestimating their interest or understating their interest, because they ended

0:25:45.240 --> 0:25:50.520
<v Speaker 4>up isolating, synthesizing and then producing an elemental analysis of

0:25:50.560 --> 0:25:55.960
<v Speaker 4>the serum vasoconstrictor, which they named seratonin in nineteen forty eight,

0:25:56.280 --> 0:25:58.280
<v Speaker 4>not knowing that it already had a name.

0:25:58.760 --> 0:26:00.880
<v Speaker 5>Right, Yeah, they went out.

0:26:01.200 --> 0:26:03.960
<v Speaker 4>They yeah, they won out. I mean, and I think

0:26:04.000 --> 0:26:08.560
<v Speaker 4>they won out because it was the serum part. The

0:26:08.560 --> 0:26:12.960
<v Speaker 4>pharmaceutical company liked the name sarah like SCR to indicate

0:26:12.960 --> 0:26:14.000
<v Speaker 4>that it was found in the serum.

0:26:14.680 --> 0:26:16.159
<v Speaker 3>I don't know first they named it.

0:26:16.240 --> 0:26:21.000
<v Speaker 4>Yeah, five hydroxy trip trip to mean. But the pharmaceutical company, yeah,

0:26:21.040 --> 0:26:23.280
<v Speaker 4>they were like serotonin.

0:26:22.800 --> 0:26:24.800
<v Speaker 5>I mean, that is still what it is called. It's

0:26:24.840 --> 0:26:29.160
<v Speaker 5>like five hydrox yeah, five h yeah yeah, five ht yes.

0:26:29.600 --> 0:26:33.960
<v Speaker 4>But they yeah, they wanted a catchier which I appreciate.

0:26:34.320 --> 0:26:37.320
<v Speaker 4>I five hydroxy trip to mean is a hard is

0:26:37.320 --> 0:26:40.600
<v Speaker 4>a harder one to say, for sure. But within a

0:26:40.680 --> 0:26:44.040
<v Speaker 4>few years this research group realized that, oh wait a second,

0:26:44.119 --> 0:26:47.280
<v Speaker 4>this thing already like has been described, and so enter

0:26:47.320 --> 0:26:49.520
<v Speaker 4>I mean and serotonin actually the same thing. And then

0:26:49.560 --> 0:26:52.200
<v Speaker 4>they published this in a paper saying like, hey, these

0:26:52.440 --> 0:26:54.679
<v Speaker 4>these two things are the same. And this kind of

0:26:54.680 --> 0:26:58.720
<v Speaker 4>like expanded the interest and sort of the knowledge base

0:26:58.760 --> 0:27:02.160
<v Speaker 4>of what this thing does. Right, But at the time

0:27:02.840 --> 0:27:07.880
<v Speaker 4>it was still thought of as primarily a vasoconstrictor and

0:27:08.000 --> 0:27:12.119
<v Speaker 4>involved in smooth muscle contraction. Its role as a neurotransmitter

0:27:12.400 --> 0:27:16.159
<v Speaker 4>had not yet been uncovered, and when it was, it

0:27:16.160 --> 0:27:19.760
<v Speaker 4>would launch serotonin out of the realm of like cool

0:27:19.800 --> 0:27:22.879
<v Speaker 4>physiological things like this is neat, maybe this does something

0:27:22.960 --> 0:27:42.879
<v Speaker 4>in mollusks and into the burgeoning field of brain chemistry.

0:27:43.680 --> 0:27:47.160
<v Speaker 4>There was a researcher named Betty Tuurog who had been

0:27:47.160 --> 0:27:53.960
<v Speaker 4>interested in understanding a phenomenon in the muscles of muscles. Okay, yeah,

0:27:54.000 --> 0:27:58.679
<v Speaker 4>the organized the vibe out and she had identified serotonin

0:27:58.720 --> 0:28:02.560
<v Speaker 4>as a likely candidate for were the mystery neurotransmitter that

0:28:02.560 --> 0:28:05.440
<v Speaker 4>that she had suspected of playing a role. The structures

0:28:05.480 --> 0:28:11.200
<v Speaker 4>seemed to match, and analyzes confirmed her hypothesis, making serotonin

0:28:11.280 --> 0:28:16.639
<v Speaker 4>a neurotransmitter. But this landmark finding had trouble getting published

0:28:17.040 --> 0:28:19.440
<v Speaker 4>because the editor of the journal that she submitted to

0:28:19.560 --> 0:28:21.560
<v Speaker 4>sat on it for two years because he was like,

0:28:21.640 --> 0:28:25.399
<v Speaker 4>this is not worthy of review two years, and he

0:28:25.520 --> 0:28:29.560
<v Speaker 4>only sent it out for review after her advisor was like, hey, man, like,

0:28:29.640 --> 0:28:30.200
<v Speaker 4>what's the deal.

0:28:30.240 --> 0:28:32.120
<v Speaker 3>Can you please review this? This might be a.

0:28:32.080 --> 0:28:37.200
<v Speaker 4>Pretty huge finding. Yeah, And it was. It didn't get

0:28:37.240 --> 0:28:39.200
<v Speaker 4>a ton of traction. It's funny because it came out

0:28:39.280 --> 0:28:42.240
<v Speaker 4>I think after another paper that got a lot more traction,

0:28:42.320 --> 0:28:46.120
<v Speaker 4>which makes sense. But anyway, so TWAA didn't stop there

0:28:46.240 --> 0:28:49.560
<v Speaker 4>with just this like this is a neurotransmitter. She reasoned

0:28:49.640 --> 0:28:54.520
<v Speaker 4>that if saratonin was an important neurotransmitter in invertebrates like muscles,

0:28:55.120 --> 0:28:59.400
<v Speaker 4>it was probably invertebrates too. One of her advisors was like,

0:28:59.640 --> 0:29:02.120
<v Speaker 4>I don't so, I think this is just a this

0:29:02.200 --> 0:29:04.920
<v Speaker 4>is just just an invert thing. Yeah, just an invert thing,

0:29:05.120 --> 0:29:12.520
<v Speaker 4>just like a very you know, like primitive transmitter of course, right, Yeah,

0:29:12.560 --> 0:29:15.560
<v Speaker 4>but she got the last laugh because she isolated serotonin

0:29:15.720 --> 0:29:19.520
<v Speaker 4>not only from muscle nervous tissue like in the bivalve,

0:29:20.000 --> 0:29:24.640
<v Speaker 4>but from mammalian brain as well, and her resulting nineteen

0:29:24.680 --> 0:29:28.560
<v Speaker 4>fifty three publications started a new chapter or even a

0:29:28.600 --> 0:29:33.000
<v Speaker 4>new book really on serotonin in brain function and mental illness.

0:29:33.600 --> 0:29:34.440
<v Speaker 5>Fascinating.

0:29:34.600 --> 0:29:38.640
<v Speaker 4>So that is how serotonin was like discovered and then

0:29:38.720 --> 0:29:44.040
<v Speaker 4>discovered to be a neurotransmitter in the mammalian brain.

0:29:44.240 --> 0:29:47.120
<v Speaker 5>Something that was in the mammalian brain that potentially was

0:29:47.120 --> 0:29:49.480
<v Speaker 5>having effects. Yes, in the mammalian brain.

0:29:49.640 --> 0:29:50.440
<v Speaker 3>What do we do with this?

0:29:50.640 --> 0:29:50.800
<v Speaker 5>Yeah?

0:29:50.960 --> 0:29:56.400
<v Speaker 4>So since the nineteen forties, LSD fascinated those who knew

0:29:56.400 --> 0:30:00.680
<v Speaker 4>about it, of course that dead who also wondered at

0:30:00.680 --> 0:30:05.000
<v Speaker 4>its psychedelic properties. So a couple of these researchers, Dilworth

0:30:05.040 --> 0:30:09.000
<v Speaker 4>Woolley and Elliott Shaw followed these developments on serotonin with

0:30:09.080 --> 0:30:14.600
<v Speaker 4>great interest because the neurotransmitter was structurally very similar to LSD.

0:30:15.640 --> 0:30:18.920
<v Speaker 4>So when they like, when that chemical structure was published

0:30:18.960 --> 0:30:22.440
<v Speaker 4>by that first group, they were like, this is this

0:30:22.560 --> 0:30:28.120
<v Speaker 4>is really interesting and they thought, Okay, maybe because it's

0:30:28.160 --> 0:30:32.000
<v Speaker 4>so structurally similar to LSD, does this mean that LSD

0:30:32.080 --> 0:30:36.320
<v Speaker 4>could act as a block, like fitting into serotonin's receptors

0:30:36.360 --> 0:30:40.800
<v Speaker 4>and preventing it from working. Okay, And this concept of

0:30:40.840 --> 0:30:44.960
<v Speaker 4>like a lock and key for neurotransmitters would form the

0:30:45.000 --> 0:30:48.760
<v Speaker 4>basis for understanding how drugs could act as either mimicking

0:30:48.840 --> 0:30:52.239
<v Speaker 4>a natural substance like a neurotransmitter or a hormone, or

0:30:52.280 --> 0:30:56.360
<v Speaker 4>blocking its action like LSD did to serotonin. So it

0:30:56.400 --> 0:30:59.920
<v Speaker 4>was like, what does this do? Can this either flood

0:31:00.200 --> 0:31:03.719
<v Speaker 4>brain with more of the same and then there are

0:31:03.720 --> 0:31:06.280
<v Speaker 4>all the receptors are filled in the way that it

0:31:06.320 --> 0:31:08.800
<v Speaker 4>normally and things continued to act the way they would,

0:31:08.880 --> 0:31:12.800
<v Speaker 4>but maybe like kind of elevated elevated or would it

0:31:12.840 --> 0:31:17.400
<v Speaker 4>block block the action exactly? Yeah, And so sure enough,

0:31:17.480 --> 0:31:20.240
<v Speaker 4>when it came to LSD, that is exactly what happened

0:31:20.240 --> 0:31:23.920
<v Speaker 4>when someone tried it out. It blocked serotonin and so

0:31:24.040 --> 0:31:28.480
<v Speaker 4>receptors receptors, and so for Woolley and Shaw, this raised

0:31:28.480 --> 0:31:30.800
<v Speaker 4>the question of whether serotonin could play a role in

0:31:30.880 --> 0:31:35.320
<v Speaker 4>mental illness because they had observed that people who were

0:31:35.560 --> 0:31:40.400
<v Speaker 4>on LSD could experience mental disturbances that looked very similar

0:31:40.520 --> 0:31:44.360
<v Speaker 4>to something like schizophrenia, for example, And so what if

0:31:44.400 --> 0:31:48.640
<v Speaker 4>those disturbances were the results of the drug blocking serotonin.

0:31:49.600 --> 0:31:52.840
<v Speaker 4>So maybe, to extend this even further, they thought, Okay,

0:31:52.840 --> 0:31:56.200
<v Speaker 4>maybe it's not just about someone on LSD and these disturbances,

0:31:56.200 --> 0:32:02.080
<v Speaker 4>but what if mental illnesses, mental health disorders like schizophrenia,

0:32:02.840 --> 0:32:11.959
<v Speaker 4>are actually some sort of mismatch or decrease in serotonin serotonin. Yeah,

0:32:12.000 --> 0:32:15.960
<v Speaker 4>And so subsequent experiments and closer scrutiny in this idea

0:32:16.000 --> 0:32:18.640
<v Speaker 4>showed that it didn't quite work out that way, particularly

0:32:18.680 --> 0:32:21.720
<v Speaker 4>when it came to schizophrenia, But there was something to

0:32:21.840 --> 0:32:26.000
<v Speaker 4>the idea, and researchers began testing other drugs that could

0:32:26.080 --> 0:32:29.320
<v Speaker 4>either deplete or replenish stores of serotonin.

0:32:29.560 --> 0:32:29.840
<v Speaker 5>Okay.

0:32:30.440 --> 0:32:33.720
<v Speaker 4>One of these serotonin depleters was recurpene.

0:32:34.600 --> 0:32:36.120
<v Speaker 3>Does this sound familiar? Yeah?

0:32:36.280 --> 0:32:38.120
<v Speaker 5>Okay, did we talk about it on the podcast or

0:32:39.080 --> 0:32:40.240
<v Speaker 5>you the podcast?

0:32:40.360 --> 0:32:41.000
<v Speaker 3>Yeah?

0:32:41.960 --> 0:32:43.720
<v Speaker 4>Because I was like, this sounds familiar, So I did

0:32:43.760 --> 0:32:46.840
<v Speaker 4>a control f of our transcripts.

0:32:46.920 --> 0:32:48.440
<v Speaker 3>Sure enough, and yeah.

0:32:48.520 --> 0:32:51.760
<v Speaker 4>So recurping is an alkaloid from the snake wood plant

0:32:52.160 --> 0:32:57.160
<v Speaker 4>Rau Wolfia serpentina, and it was examined as a possible

0:32:57.200 --> 0:33:02.239
<v Speaker 4>treatment for hypertension. And then but this is not this

0:33:02.320 --> 0:33:04.600
<v Speaker 4>is not when we I'll tell you about it in

0:33:04.640 --> 0:33:07.400
<v Speaker 4>a second, okay, Okay, Okay, First I'm going to get

0:33:07.440 --> 0:33:10.760
<v Speaker 4>to like the serotonin part. So researchers found that people

0:33:10.800 --> 0:33:14.960
<v Speaker 4>were given recurping, uh, and then they tended to become depressed,

0:33:15.760 --> 0:33:19.120
<v Speaker 4>which was resolved if treatment stopped. So they were like,

0:33:19.160 --> 0:33:22.640
<v Speaker 4>what is recurping doing that is causing these symptoms of depression?

0:33:23.440 --> 0:33:27.520
<v Speaker 4>And it seems very clearly resurping because it stops with

0:33:27.560 --> 0:33:28.360
<v Speaker 4>stopping the treatment.

0:33:28.400 --> 0:33:29.080
<v Speaker 3>Stopping treatment.

0:33:29.160 --> 0:33:31.680
<v Speaker 4>Yeah okay, And so in tests carried out on rabbits,

0:33:31.760 --> 0:33:36.240
<v Speaker 4>resurping was found not only two deplete stores of serotonin,

0:33:37.360 --> 0:33:41.320
<v Speaker 4>which was a big contender, but also nouropinephrin, and a

0:33:41.440 --> 0:33:44.400
<v Speaker 4>newly discovered neurotransmitter called dopamine.

0:33:44.440 --> 0:33:44.920
<v Speaker 5>Dopamine.

0:33:45.200 --> 0:33:48.960
<v Speaker 4>Yes, so we talked about this in our Parkinson's arkansans.

0:33:49.560 --> 0:33:53.200
<v Speaker 4>This is how el dopa was found because they they

0:33:53.240 --> 0:33:55.880
<v Speaker 4>found that when you when you gave rabbits high doses

0:33:55.920 --> 0:34:01.080
<v Speaker 4>of recurping, they tended to exhibit some of like paraals symptoms.

0:34:00.680 --> 0:34:02.200
<v Speaker 5>Similar to Parkins.

0:34:03.080 --> 0:34:05.040
<v Speaker 4>And then they added el dopa and that sort of

0:34:05.080 --> 0:34:07.960
<v Speaker 4>snapped them out of it, ultimately meaning the researchers to

0:34:08.000 --> 0:34:08.920
<v Speaker 4>discover dopamine.

0:34:09.480 --> 0:34:09.800
<v Speaker 3>Wow.

0:34:09.840 --> 0:34:12.920
<v Speaker 4>Okay, but what does this all mean for depression and

0:34:13.000 --> 0:34:16.120
<v Speaker 4>under and other mental health disorders? Like talked about Parkinson's,

0:34:16.120 --> 0:34:19.319
<v Speaker 4>I've talked about hypertension, I've talked about schizophrenia. We haven't

0:34:19.320 --> 0:34:24.560
<v Speaker 4>really talked about depression yet. Okay, the precise mechanism wasn't clear,

0:34:25.520 --> 0:34:31.719
<v Speaker 4>but researchers hypothesized that maybe it was depletion of serotonin, dopamine,

0:34:31.840 --> 0:34:38.160
<v Speaker 4>and nouropinephrine that underlay the development of depression, and that

0:34:38.360 --> 0:34:42.359
<v Speaker 4>accesses might also lead to psychosis, especially when it came

0:34:42.440 --> 0:34:46.480
<v Speaker 4>to dopamine. So, in other words, mental illness might be

0:34:46.520 --> 0:34:50.840
<v Speaker 4>a result not of psychological imbalances, but rather chemical ones.

0:34:51.600 --> 0:34:55.640
<v Speaker 4>And so this is really when like the imbalance sort

0:34:55.680 --> 0:34:59.080
<v Speaker 4>of notion of mental health illnesses began.

0:34:59.200 --> 0:35:02.640
<v Speaker 5>And specific imbalances of those three like monozines.

0:35:02.719 --> 0:35:07.320
<v Speaker 4>Yeah, the monoamine or catacholamine hypothesis of depression was essentially

0:35:07.480 --> 0:35:09.480
<v Speaker 4>born out of these experiments.

0:35:09.520 --> 0:35:11.760
<v Speaker 5>Okay, okay, yeah, okay.

0:35:11.760 --> 0:35:14.240
<v Speaker 4>So I want to take a second here to ground

0:35:14.280 --> 0:35:17.960
<v Speaker 4>ourselves in what depression meant. At the time this research

0:35:18.040 --> 0:35:21.000
<v Speaker 4>was happening, this is the nineteen fifties, nineteen sixties or so,

0:35:22.280 --> 0:35:27.359
<v Speaker 4>it was rarely diagnosed. It wasn't often even included as

0:35:27.400 --> 0:35:30.440
<v Speaker 4>a separate category of diagnosis. Like there was really like

0:35:30.760 --> 0:35:36.200
<v Speaker 4>depression as a diagnosis. When patients expressed symptoms that today

0:35:36.239 --> 0:35:40.800
<v Speaker 4>we would associate with depression, so despondent, low energy, chronically sad,

0:35:41.320 --> 0:35:45.040
<v Speaker 4>something that would interfere with their everyday life, they were

0:35:45.160 --> 0:35:49.360
<v Speaker 4>usually ascribed to an expression of someone's anxiety, so like

0:35:49.480 --> 0:35:52.040
<v Speaker 4>anxiety was thought to be at the heart of most

0:35:52.120 --> 0:35:55.440
<v Speaker 4>mental health disorders at the time, some clinicians felt that

0:35:55.520 --> 0:35:58.960
<v Speaker 4>depressive symptoms were like a self defense against anxiety. Oh,

0:35:58.960 --> 0:36:03.000
<v Speaker 4>I can't work too much if I just become apathetic.

0:36:03.239 --> 0:36:04.120
<v Speaker 5>That was sort of like.

0:36:04.080 --> 0:36:08.080
<v Speaker 4>The idea that I think decission fell into Yeah, it is.

0:36:08.160 --> 0:36:12.920
<v Speaker 4>It is really interesting, especially considering like today sort of

0:36:12.960 --> 0:36:16.600
<v Speaker 4>the lines between anxiety and depression and the yeah.

0:36:16.640 --> 0:36:18.719
<v Speaker 5>Yeah, I mean there is. There is so much overlap

0:36:18.800 --> 0:36:22.279
<v Speaker 5>with anxiety symptoms of anxiety and depression, and a lot

0:36:22.280 --> 0:36:24.600
<v Speaker 5>of times depression is a lot harder to treat if

0:36:24.640 --> 0:36:27.520
<v Speaker 5>there is an anxiety component versus if there isn't.

0:36:29.000 --> 0:36:29.239
<v Speaker 3>Yeah.

0:36:29.239 --> 0:36:30.719
<v Speaker 5>So that's really interesting, it is.

0:36:30.960 --> 0:36:35.000
<v Speaker 4>It's yeah, the history of anyway we could yeah.

0:36:34.920 --> 0:36:37.880
<v Speaker 5>I know that, like the history of psychiatry. Wo oh,

0:36:38.800 --> 0:36:39.880
<v Speaker 5>that's not this episode.

0:36:40.000 --> 0:36:42.360
<v Speaker 3>That not this episode. Yeah.

0:36:42.400 --> 0:36:47.320
<v Speaker 4>And so there was a distinct diagnosis for depression separate

0:36:47.320 --> 0:36:51.000
<v Speaker 4>from anxiety, but it was reserved for extreme, like really

0:36:51.040 --> 0:36:54.040
<v Speaker 4>severe cases that involved psychosis.

0:36:54.440 --> 0:36:55.320
<v Speaker 5>Okay. Interesting.

0:36:55.440 --> 0:36:59.080
<v Speaker 4>So from the nineteen fifty two DSM describing quote unquote

0:36:59.120 --> 0:37:04.440
<v Speaker 4>psychotic depression reaction quote, these patients are severely depressed and

0:37:04.520 --> 0:37:08.920
<v Speaker 4>manifest evidence of gross misinterpretation of reality, including at times

0:37:08.960 --> 0:37:14.520
<v Speaker 4>delusions and hallucinations end quote. Okay, so it's it's not again,

0:37:14.600 --> 0:37:19.880
<v Speaker 4>it's a very narrow definition compared to what we have today, exactly. Yeah,

0:37:19.920 --> 0:37:23.880
<v Speaker 4>And things like melancholia or melancholy had also been a

0:37:23.920 --> 0:37:26.560
<v Speaker 4>popular diagnosis in the late eighteen hundreds and into the

0:37:26.640 --> 0:37:29.560
<v Speaker 4>nineteen hundreds, and it was believed to have a biological

0:37:29.600 --> 0:37:37.040
<v Speaker 4>basis until Freud. That biological basis and melancholia in general

0:37:37.120 --> 0:37:39.719
<v Speaker 4>kind of fell out of favor as Freudian theory took over,

0:37:40.320 --> 0:37:42.360
<v Speaker 4>which held that biology had nothing to do with it.

0:37:42.640 --> 0:37:44.400
<v Speaker 5>Yeah, it was all your mom and stuff.

0:37:44.440 --> 0:37:45.120
<v Speaker 3>It's all your mom.

0:37:45.360 --> 0:37:51.120
<v Speaker 5>Yeah, that's the conclusion of freud the end.

0:37:52.520 --> 0:37:55.080
<v Speaker 4>So all this is to say that in the nineteen

0:37:55.120 --> 0:37:59.360
<v Speaker 4>fifties and nineteen sixties, depression was not the widespread, broadly

0:37:59.400 --> 0:38:02.239
<v Speaker 4>defined cli entity that we think of today, and so

0:38:03.120 --> 0:38:08.319
<v Speaker 4>it really wasn't seen as a major problem warranting extensive

0:38:08.360 --> 0:38:13.080
<v Speaker 4>searches for effective treatment or better understanding of its underlying cause. Wow,

0:38:13.280 --> 0:38:16.600
<v Speaker 4>the framing of it really prevented interest. I think, yeah,

0:38:16.800 --> 0:38:17.759
<v Speaker 4>and like consideration.

0:38:18.040 --> 0:38:19.239
<v Speaker 3>Yeah.

0:38:19.520 --> 0:38:23.719
<v Speaker 4>And some treatments did exist, such as electroconvulsive therapy, which

0:38:23.800 --> 0:38:26.640
<v Speaker 4>was used for severely depressed patients with psychosis in the

0:38:26.680 --> 0:38:31.000
<v Speaker 4>nineteen forties, and it seemed effective in the short term,

0:38:31.040 --> 0:38:33.520
<v Speaker 4>but no one knew why, and it quickly fell out

0:38:33.560 --> 0:38:37.560
<v Speaker 4>of favor as long term negative effects emerged, like extreme

0:38:37.600 --> 0:38:43.319
<v Speaker 4>memory loss and other things. Amphetamines were prescribed for the

0:38:43.360 --> 0:38:46.480
<v Speaker 4>Blues in the nineteen forties and the nineteen fifties.

0:38:46.640 --> 0:38:47.160
<v Speaker 5>Okay.

0:38:47.320 --> 0:38:52.719
<v Speaker 4>And then there were combination amphetamines sedatives to treat anxiety

0:38:52.840 --> 0:38:54.799
<v Speaker 4>and the depressive symptoms that came with it.

0:38:55.080 --> 0:39:01.879
<v Speaker 5>Oh gosh, okay, upper runed downer, mix it all up, Okay, great, yep.

0:39:02.760 --> 0:39:07.399
<v Speaker 4>But again none of these drugs were antidepressants. They were

0:39:07.480 --> 0:39:10.200
<v Speaker 4>treating what was understood at the time to be a

0:39:10.239 --> 0:39:17.719
<v Speaker 4>symptom of anxiety. What turned things around was tuberculosis.

0:39:18.560 --> 0:39:22.400
<v Speaker 5>Stop it, everything is tuberculosis.

0:39:22.480 --> 0:39:23.520
<v Speaker 3>I was just, yeah, I have here.

0:39:23.600 --> 0:39:26.600
<v Speaker 4>John Green was right, everything really is tuberculosis.

0:39:26.920 --> 0:39:30.080
<v Speaker 5>Stop it, yes, tell me more, Okay, okay.

0:39:30.360 --> 0:39:33.279
<v Speaker 4>So, as the nineteen fifties rolled around, the hunt for

0:39:33.360 --> 0:39:36.520
<v Speaker 4>an effective tuberculosis treatment had been going on for decades

0:39:36.600 --> 0:39:40.480
<v Speaker 4>with how much success. And then a new drug called

0:39:40.719 --> 0:39:44.040
<v Speaker 4>iproniazid okay, m hmm came on the scene. And if

0:39:44.080 --> 0:39:46.280
<v Speaker 4>you listen to our book club episode on the Black

0:39:46.320 --> 0:39:49.440
<v Speaker 4>Angels by Maria Smilios, this is one of the new

0:39:49.440 --> 0:39:52.920
<v Speaker 4>anti tuberculosis drugs that the nurses at Seaview Hospital on

0:39:52.960 --> 0:39:55.040
<v Speaker 4>Staten Island tested out on their patients.

0:39:55.120 --> 0:39:55.560
<v Speaker 5>Okay.

0:39:56.400 --> 0:39:59.520
<v Speaker 4>And when these patients, when these tuberculosis patients were getting

0:39:59.560 --> 0:40:04.120
<v Speaker 4>this drug, their moods improved, their appetite increased. There were

0:40:04.120 --> 0:40:09.840
<v Speaker 4>even reports of dancing in the wards. Whoa yep. Initially,

0:40:09.920 --> 0:40:14.480
<v Speaker 4>these positive side effects of euphoria, psychostimulation, increased appetite, improved

0:40:14.520 --> 0:40:18.640
<v Speaker 4>sleep weren't of much interest to the drug manufacturer, especially

0:40:18.920 --> 0:40:21.960
<v Speaker 4>since ipronized It only did so so when it came

0:40:21.960 --> 0:40:27.000
<v Speaker 4>to treating tuberculosis, its sister drug, ionized It did much better.

0:40:28.160 --> 0:40:31.480
<v Speaker 4>But the pictures of dancing patients that seeview caught the

0:40:31.480 --> 0:40:36.440
<v Speaker 4>attention of one psychiatrist, doctor Nathan Klein, who wondered whether

0:40:36.560 --> 0:40:39.600
<v Speaker 4>ipronized It held the answer to a question that had

0:40:39.680 --> 0:40:44.239
<v Speaker 4>long interested him. If something like schizophrenia was caused by

0:40:44.320 --> 0:40:47.640
<v Speaker 4>an excess of psychic energy quote unquote, which is kind

0:40:47.640 --> 0:40:50.200
<v Speaker 4>of the idea at the time, could depression be caused

0:40:50.239 --> 0:40:54.799
<v Speaker 4>by a lack of it? Could this tuberculosis drug, with

0:40:54.880 --> 0:41:00.720
<v Speaker 4>its euphoric effects increase psychic energy. So began a trial

0:41:01.040 --> 0:41:04.520
<v Speaker 4>using Iproniazid to treat his patients who had severe depression

0:41:04.719 --> 0:41:08.359
<v Speaker 4>at the state hospital where he worked. He detected an

0:41:08.360 --> 0:41:13.160
<v Speaker 4>improvement in seventy percent of them, wow, which he reported

0:41:13.200 --> 0:41:17.319
<v Speaker 4>in nineteen fifty seven, and so with this, iproniazid came

0:41:17.360 --> 0:41:20.680
<v Speaker 4>the became the first of our modern antidepressants on the

0:41:20.680 --> 0:41:27.560
<v Speaker 4>market ANDI or a monoamine oxidase inhibitor. Isn't that unbelievable

0:41:28.360 --> 0:41:30.319
<v Speaker 4>from tuberculosculosis.

0:41:30.840 --> 0:41:33.200
<v Speaker 5>Wow, Jock Green had it right.

0:41:33.520 --> 0:41:34.279
<v Speaker 3>He had it right.

0:41:34.800 --> 0:41:37.120
<v Speaker 4>I just I love that it was this researcher, the

0:41:37.160 --> 0:41:39.600
<v Speaker 4>psychiatrist who saw these pictures and was.

0:41:39.520 --> 0:41:42.520
<v Speaker 5>Like, whoa they seem pressed?

0:41:42.719 --> 0:41:42.799
<v Speaker 1>Ye?

0:41:43.600 --> 0:41:44.560
<v Speaker 3>Can we use this?

0:41:45.280 --> 0:41:46.359
<v Speaker 5>How interesting?

0:41:46.600 --> 0:41:49.720
<v Speaker 3>Yeah, that's it's amazing. Yeah.

0:41:49.760 --> 0:41:54.680
<v Speaker 4>And the popularity of iproniazid and other similar MAOIs that

0:41:54.920 --> 0:41:58.520
<v Speaker 4>quickly appeared at following iproniazid in the late nineteen fifties,

0:41:58.760 --> 0:42:01.719
<v Speaker 4>it was they were fairly lived as a as a

0:42:01.760 --> 0:42:06.239
<v Speaker 4>popular antidepressant because while they did seem to be effective

0:42:06.280 --> 0:42:09.719
<v Speaker 4>in treating depression, they came with some pretty nasty side

0:42:09.719 --> 0:42:14.960
<v Speaker 4>effects constipation, difficulty urinating, even jaundice. Death could occur if

0:42:14.960 --> 0:42:16.720
<v Speaker 4>someone eat cheese or chocolate.

0:42:17.120 --> 0:42:18.920
<v Speaker 5>Yeah, and drug tresines.

0:42:19.600 --> 0:42:22.600
<v Speaker 4>Drug companies withdrew the drug and it would soon be

0:42:22.680 --> 0:42:26.759
<v Speaker 4>replaced by another class of drugs, the tricyclic antidepressants or TCAs,

0:42:27.120 --> 0:42:28.960
<v Speaker 4>which were approved.

0:42:28.520 --> 0:42:29.680
<v Speaker 3>In nineteen fifty nine.

0:42:30.239 --> 0:42:32.920
<v Speaker 4>And these had first been tested as a possible treatment

0:42:32.960 --> 0:42:36.759
<v Speaker 4>for schizophrenia, where they were found to be not effective. No,

0:42:37.680 --> 0:42:42.000
<v Speaker 4>but definitely not definitely not Again it was all like depletion,

0:42:42.560 --> 0:42:45.359
<v Speaker 4>you know, that great sort of the sea cell of

0:42:45.440 --> 0:42:49.359
<v Speaker 4>what do we want the balance? Yeah, exactly, But these

0:42:49.920 --> 0:42:53.640
<v Speaker 4>these TCAs did show some positive impact for people with

0:42:53.719 --> 0:42:58.640
<v Speaker 4>depressive symptoms. At side effects again left something to be desired, dizziness,

0:42:58.719 --> 0:43:02.359
<v Speaker 4>memory impairment, drowsing, et cetera. But I just think it's

0:43:02.520 --> 0:43:05.400
<v Speaker 4>amazing that we keep finding antidepressants when we're not looking,

0:43:06.160 --> 0:43:08.920
<v Speaker 4>which speaks to this phenomenon that I mentioned at the

0:43:09.040 --> 0:43:11.319
<v Speaker 4>very beginning, like sometimes we have these drugs that are

0:43:11.320 --> 0:43:14.759
<v Speaker 4>effective for certain conditions we don't know why, right, And

0:43:14.840 --> 0:43:18.480
<v Speaker 4>stories like MAOIs and TCAs show us that we don't

0:43:18.520 --> 0:43:23.040
<v Speaker 4>necessarily have to know how something works to develop effective treatments.

0:43:24.000 --> 0:43:27.040
<v Speaker 4>And even if we think we know, like we thought

0:43:27.080 --> 0:43:30.680
<v Speaker 4>we did with SSRIs, because this was like this was

0:43:30.680 --> 0:43:35.840
<v Speaker 4>a more targeted drug development, and we're proven wrong about

0:43:35.840 --> 0:43:39.879
<v Speaker 4>our initial hypothesis or not totally right, we can still

0:43:39.920 --> 0:43:40.600
<v Speaker 4>make a difference.

0:43:40.840 --> 0:43:41.120
<v Speaker 5>Yeah.

0:43:41.360 --> 0:43:44.120
<v Speaker 4>Yeah, Okay, so we're finally at the point in the

0:43:44.120 --> 0:43:46.000
<v Speaker 4>story where SSRIs.

0:43:45.480 --> 0:43:46.240
<v Speaker 3>Come onto the scene.

0:43:46.440 --> 0:43:48.879
<v Speaker 4>Okay, it's taken us a little bit to get here,

0:43:49.239 --> 0:43:52.520
<v Speaker 4>but I feel like it was important to understand the

0:43:52.520 --> 0:43:57.480
<v Speaker 4>big picture, like, oh yeah, it's just fascinating, you know,

0:43:57.640 --> 0:44:00.359
<v Speaker 4>from two billion, three billion years ago all the way to.

0:44:00.760 --> 0:44:02.239
<v Speaker 5>Till the day in nineteen sixties.

0:44:02.360 --> 0:44:03.680
<v Speaker 3>Nineteen sixties, there you go.

0:44:05.000 --> 0:44:10.799
<v Speaker 4>And so the advent and effectiveness of MAOIs and TCAs

0:44:11.200 --> 0:44:13.960
<v Speaker 4>kind of lent support to the idea that depression and

0:44:14.200 --> 0:44:18.920
<v Speaker 4>other mental health disorders are related in some way to serotonin, orpinephrine,

0:44:18.960 --> 0:44:23.399
<v Speaker 4>and dopamine. So like there's something to the monoamine hypothesis

0:44:23.400 --> 0:44:28.000
<v Speaker 4>of depression, right, And how exactly they were involved was

0:44:28.480 --> 0:44:34.080
<v Speaker 4>unclear since they both worked in different ways TCAs and MAOIs, Right,

0:44:34.120 --> 0:44:36.360
<v Speaker 4>they both led to kind of the same end result.

0:44:36.719 --> 0:44:40.600
<v Speaker 5>Right, you're increasing the amount of these neurotransmitters.

0:44:39.800 --> 0:44:41.919
<v Speaker 4>Exactly, and how you're doing that, that's not really sure.

0:44:41.960 --> 0:44:43.560
<v Speaker 4>And how is it improving your symptoms?

0:44:43.560 --> 0:44:44.560
<v Speaker 5>I would really know. No.

0:44:45.160 --> 0:44:49.480
<v Speaker 4>And so it seemed like antidepressants were on a trajectory

0:44:49.520 --> 0:44:53.319
<v Speaker 4>of incremental improvements. But like we talked about, those two

0:44:53.400 --> 0:44:57.279
<v Speaker 4>existing classes had some serious drawbacks with their prevalent and

0:44:57.320 --> 0:45:01.600
<v Speaker 4>sometimes serious or deadly side effects, which were due in

0:45:01.680 --> 0:45:05.200
<v Speaker 4>part to how they weren't super specific. They were kind

0:45:05.200 --> 0:45:10.880
<v Speaker 4>of ramping up all of those three dopamine, norpinephrin, serotonin.

0:45:10.920 --> 0:45:13.640
<v Speaker 4>It was kind of just like across the board. And so,

0:45:14.280 --> 0:45:17.200
<v Speaker 4>you know, some researchers thought, well, what if we could

0:45:17.200 --> 0:45:19.560
<v Speaker 4>make these more specific, What if you could target just

0:45:19.719 --> 0:45:23.000
<v Speaker 4>one of these neurotransmitters, Maybe that would help with the

0:45:23.040 --> 0:45:25.920
<v Speaker 4>side effects, Maybe that would get to the root underlying

0:45:26.160 --> 0:45:30.680
<v Speaker 4>cause of these disorders. And so by the late nineteen sixties,

0:45:30.840 --> 0:45:34.759
<v Speaker 4>interest had gathered specifically on the role that serotonin might

0:45:34.840 --> 0:45:39.840
<v Speaker 4>play in depression. Specifically, again it's depletion, with the logic

0:45:39.920 --> 0:45:44.560
<v Speaker 4>following that if you could restore serotonin, you could alleviate depression.

0:45:45.640 --> 0:45:48.080
<v Speaker 4>We know that that's.

0:45:47.280 --> 0:45:48.200
<v Speaker 3>Not the case.

0:45:48.560 --> 0:45:49.960
<v Speaker 5>It's not exactly the truth.

0:45:50.040 --> 0:45:53.960
<v Speaker 4>It's not exactly the truth, but it was a it

0:45:54.000 --> 0:45:58.960
<v Speaker 4>was a hypothesis. Yeah, it's not Yeah, it's anyway, there's

0:45:58.960 --> 0:46:01.759
<v Speaker 4>a lot of us were starting points, the starting point exactly.

0:46:01.880 --> 0:46:03.040
<v Speaker 5>Yeah, And so.

0:46:02.960 --> 0:46:06.000
<v Speaker 4>Pharmaceutical companies set their sites on making a compound that

0:46:06.120 --> 0:46:12.040
<v Speaker 4>prevented the reuptake of serotonin at serotonin transporters, specifically, meaning

0:46:12.040 --> 0:46:15.560
<v Speaker 4>that it had reduced affinity for Nora Bernephrin. So put

0:46:15.560 --> 0:46:18.799
<v Speaker 4>that jargon another way, and you've got a selective serotonin

0:46:18.840 --> 0:46:20.400
<v Speaker 4>reuptake inhibitor SSR.

0:46:20.920 --> 0:46:21.840
<v Speaker 5>Yeah.

0:46:22.160 --> 0:46:25.160
<v Speaker 4>Eli Lilly found success in nineteen seventy two with a

0:46:25.200 --> 0:46:29.239
<v Speaker 4>compound that they called fluoxetine, and thirteen years later it

0:46:29.239 --> 0:46:32.719
<v Speaker 4>became the first SSRI approved by the FDA under the

0:46:32.760 --> 0:46:38.239
<v Speaker 4>trade name Prozac. And it is interesting to me that

0:46:38.400 --> 0:46:45.360
<v Speaker 4>with Prozac with fluoxetine, we did have this plan, here's

0:46:45.440 --> 0:46:47.680
<v Speaker 4>what the drug that we want to make, and here's

0:46:47.680 --> 0:46:49.560
<v Speaker 4>what we're going to do, and here's how we think

0:46:49.560 --> 0:46:52.440
<v Speaker 4>it works. Right, And it still didn't work out, but

0:46:52.480 --> 0:46:55.160
<v Speaker 4>it still had some effect. And it's just different than

0:46:55.239 --> 0:46:58.319
<v Speaker 4>like ipronize it, which was like, oh, tuberculosis, right.

0:46:58.480 --> 0:47:01.000
<v Speaker 5>It was much more like intentional.

0:47:01.239 --> 0:47:04.960
<v Speaker 3>It was an intentional design. Okay.

0:47:05.000 --> 0:47:11.560
<v Speaker 4>So in the time between PROZACX development and its approval,

0:47:12.000 --> 0:47:15.960
<v Speaker 4>which is, you know, decade and a half, depression had

0:47:16.040 --> 0:47:21.080
<v Speaker 4>time long time. Depression had undergone quite a transformation really,

0:47:21.440 --> 0:47:24.440
<v Speaker 4>so beginning in the late nineteen sixties, clinicians started to

0:47:24.480 --> 0:47:28.239
<v Speaker 4>think of it as separate from anxiety, or that what

0:47:28.480 --> 0:47:32.120
<v Speaker 4>had been thought of as anxiety was actually depression. So

0:47:32.160 --> 0:47:37.560
<v Speaker 4>the depression was both increasing in its prevalence as well

0:47:37.600 --> 0:47:41.440
<v Speaker 4>as broadening in its definition. Okay, So the WHO in

0:47:41.520 --> 0:47:46.120
<v Speaker 4>nineteen seventy four declared depression much more widespread than previously thought,

0:47:46.400 --> 0:47:48.800
<v Speaker 4>affecting one fifth of the global population.

0:47:50.360 --> 0:47:50.720
<v Speaker 2>Wow.

0:47:51.239 --> 0:47:53.000
<v Speaker 3>Yeah in nineteen seventy four.

0:47:53.520 --> 0:47:57.399
<v Speaker 5>In nineteen seventy four, Wow okay, huh.

0:47:57.960 --> 0:48:02.279
<v Speaker 4>And part of this transformation, and also what made such

0:48:02.400 --> 0:48:06.239
<v Speaker 4>estimates possible, was the creation of standardized scales by which

0:48:06.280 --> 0:48:11.239
<v Speaker 4>to measure and diagnose depression. These scales allowed researchers to

0:48:11.400 --> 0:48:14.799
<v Speaker 4>conduct clinical trials where they could track depression symptoms over

0:48:14.840 --> 0:48:19.360
<v Speaker 4>time and with or without treatment, and these trials revealed

0:48:19.400 --> 0:48:24.239
<v Speaker 4>that by and large, antidepressants were effective in alleviating symptoms

0:48:24.239 --> 0:48:28.680
<v Speaker 4>of depression, with some differences among formulations and of course

0:48:28.760 --> 0:48:33.799
<v Speaker 4>among different individuals, and their efficacy held whether someone could

0:48:33.800 --> 0:48:37.239
<v Speaker 4>identify specific reasons for their depression, like this thing is

0:48:37.280 --> 0:48:40.160
<v Speaker 4>going on in my life or this you know, my

0:48:40.280 --> 0:48:44.279
<v Speaker 4>dog died, my car broke down, my house was foreclosed upon,

0:48:44.760 --> 0:48:49.880
<v Speaker 4>or if they couldn't right so, in response like to

0:48:50.200 --> 0:48:53.880
<v Speaker 4>this sort of depression happens, antidepressants work whether or not

0:48:53.920 --> 0:48:57.920
<v Speaker 4>you can define a specific incident. The DSM was like,

0:48:57.960 --> 0:49:00.680
<v Speaker 4>we need to make some adjustments, and so the three

0:49:00.680 --> 0:49:05.520
<v Speaker 4>published in nineteen eighty removed any questions about life circumstances,

0:49:05.600 --> 0:49:09.400
<v Speaker 4>family history, triggers, and so forth, and its description of depression.

0:49:09.840 --> 0:49:11.440
<v Speaker 5>Ooh interesting.

0:49:11.600 --> 0:49:15.400
<v Speaker 4>Yeah, so instead it just provided a checklist of symptoms. Yeah, okay,

0:49:15.719 --> 0:49:19.279
<v Speaker 4>so because previously diagnoses depended more on whether you could

0:49:19.280 --> 0:49:22.000
<v Speaker 4>pinpoint fact life life situations.

0:49:22.320 --> 0:49:25.640
<v Speaker 5>That's so interesting, especially thinking about now, like when you

0:49:25.719 --> 0:49:27.680
<v Speaker 5>have life stressors a lot of times you're less likely

0:49:27.719 --> 0:49:32.160
<v Speaker 5>to diagnose depression real till yeah, I mean because a

0:49:32.200 --> 0:49:35.680
<v Speaker 5>certain amount of depressive symptoms are to be expected with

0:49:35.920 --> 0:49:38.080
<v Speaker 5>significant life events, right, and so then it's like a

0:49:38.120 --> 0:49:41.280
<v Speaker 5>grief reaction which you then have to separate out from depression.

0:49:41.320 --> 0:49:44.480
<v Speaker 5>So that's interesting. I mean, it can certainly lead to depression,

0:49:44.520 --> 0:49:46.719
<v Speaker 5>but it just sort of it complicates a picture more

0:49:46.719 --> 0:49:48.120
<v Speaker 5>and it sounds like in the past it was like, no,

0:49:48.239 --> 0:49:50.719
<v Speaker 5>you need to have that in order to be depressed.

0:49:51.560 --> 0:49:52.400
<v Speaker 5>How interesting.

0:49:52.880 --> 0:49:58.399
<v Speaker 4>The transformation's huge, yeah, huge, huge, And so this shift though,

0:49:58.440 --> 0:50:04.640
<v Speaker 4>what it did was it it really increased diagnoses across

0:50:04.680 --> 0:50:07.399
<v Speaker 4>the board, because now you don't have to say, oh, well,

0:50:07.760 --> 0:50:09.920
<v Speaker 4>I don't think I think you're just I think you're

0:50:09.960 --> 0:50:11.400
<v Speaker 4>just a little bored, or I think you're just a

0:50:11.440 --> 0:50:13.640
<v Speaker 4>little bumped, you know what I mean, Like, I'm not

0:50:13.680 --> 0:50:16.719
<v Speaker 4>saying that's exactly what was said, but I think legitimized

0:50:17.960 --> 0:50:21.279
<v Speaker 4>no cases of depression where it was like nonspecific right,

0:50:21.760 --> 0:50:25.840
<v Speaker 4>life events, Yeah, right. And so when Prozac hit the

0:50:25.880 --> 0:50:29.560
<v Speaker 4>market in January nineteen eighty eight, there were many more

0:50:29.600 --> 0:50:33.080
<v Speaker 4>people who sought prescriptions for this new antidepressant than there

0:50:33.120 --> 0:50:38.520
<v Speaker 4>had been in past decades. Not necessarily because depression overall

0:50:38.719 --> 0:50:43.080
<v Speaker 4>was on the rise, like because which it may may

0:50:43.160 --> 0:50:47.360
<v Speaker 4>have been just because of the world or whatever, but

0:50:47.760 --> 0:50:51.960
<v Speaker 4>also because our framing and perception of the condition had broadened.

0:50:52.040 --> 0:50:55.000
<v Speaker 4>People now had the vocabulary to describe the things that

0:50:55.040 --> 0:50:58.280
<v Speaker 4>they felt, and then they were often, though not always,

0:50:58.320 --> 0:51:01.680
<v Speaker 4>taken more seriously about the impact of this on their

0:51:01.800 --> 0:51:02.719
<v Speaker 4>day to day functioning.

0:51:02.960 --> 0:51:03.200
<v Speaker 5>Right.

0:51:04.080 --> 0:51:07.560
<v Speaker 4>By nineteen ninety, this is just two years. Within two

0:51:07.600 --> 0:51:11.040
<v Speaker 4>years of its release in the US, Prozac became the

0:51:11.080 --> 0:51:14.120
<v Speaker 4>most widely prescribed drug in North America.

0:51:15.400 --> 0:51:17.279
<v Speaker 5>Wow, and just a.

0:51:17.239 --> 0:51:20.360
<v Speaker 4>Few years later, the second most sold drug in the world.

0:51:21.560 --> 0:51:22.480
<v Speaker 5>Wow W.

0:51:24.520 --> 0:51:28.319
<v Speaker 3>This was unexpected. I don't think it illiglally anticipated.

0:51:28.360 --> 0:51:32.120
<v Speaker 4>This Prozac was not the first antidepressant or even the

0:51:32.160 --> 0:51:36.480
<v Speaker 4>first SSRI. There were other previous SSRIs but they were

0:51:36.520 --> 0:51:38.560
<v Speaker 4>never approved for the US market, and they seemed to

0:51:38.600 --> 0:51:43.600
<v Speaker 4>have more side effects, but prozac had fewer side effects,

0:51:43.640 --> 0:51:46.320
<v Speaker 4>and so it was considered a safer drug compared to

0:51:46.480 --> 0:51:50.759
<v Speaker 4>like TCAs, which meant that physicians were more likely or

0:51:50.760 --> 0:51:53.440
<v Speaker 4>felt better about prescribing it not only to their patients

0:51:53.440 --> 0:51:57.400
<v Speaker 4>who had like severe depression, but also those with milder symptoms.

0:51:58.920 --> 0:52:03.040
<v Speaker 4>The continued pop popularity of prozac and later SSRIs showed

0:52:03.040 --> 0:52:08.280
<v Speaker 4>that clearly these medications were working, but how were they working?

0:52:09.440 --> 0:52:14.319
<v Speaker 4>Even before their release, researchers knew that these SSRIs were

0:52:14.400 --> 0:52:18.920
<v Speaker 4>not acting under the hypothesis of low or imbalanced serotonin

0:52:19.000 --> 0:52:24.920
<v Speaker 4>equals depression. That idea had been rejected decades before.

0:52:26.400 --> 0:52:29.080
<v Speaker 5>It's just so fascinating that that doesn't like that is

0:52:29.120 --> 0:52:30.560
<v Speaker 5>so often left out of the story.

0:52:30.600 --> 0:52:33.760
<v Speaker 4>It doesn't get translated. It's like, yeah, people are like, oh,

0:52:34.040 --> 0:52:37.279
<v Speaker 4>serotonin is not the only thing related to depression, you know,

0:52:37.320 --> 0:52:39.960
<v Speaker 4>scream the headlines and it's yeah. All the researchers are like,

0:52:40.520 --> 0:52:41.080
<v Speaker 4>what year.

0:52:41.040 --> 0:52:43.960
<v Speaker 3>Is this right? We've known this, I was taught this.

0:52:44.440 --> 0:52:46.520
<v Speaker 5>Said that, who said that it was sorry said that.

0:52:46.520 --> 0:52:47.400
<v Speaker 3>It was Yeah.

0:52:47.680 --> 0:52:52.080
<v Speaker 4>It's a straw man argument, because if that was the hypothesis,

0:52:52.360 --> 0:52:54.840
<v Speaker 4>then they would have expected to see You would expect

0:52:54.840 --> 0:52:59.120
<v Speaker 4>to see improvement in symptoms in someone very soon after

0:52:59.160 --> 0:53:01.960
<v Speaker 4>someone starts taking SSRIs, not after weeks, which is the

0:53:02.000 --> 0:53:05.520
<v Speaker 4>timeline that we usually see. But given that these drugs

0:53:05.520 --> 0:53:09.799
<v Speaker 4>are effective, serotonin likely plays some role in depression and

0:53:09.920 --> 0:53:12.920
<v Speaker 4>other mental health disorders, maybe in like a regulatory capacity.

0:53:13.800 --> 0:53:17.439
<v Speaker 4>But even though researchers had long acknowledged that the biological

0:53:17.520 --> 0:53:21.799
<v Speaker 4>underpinnings of depression are more complicated than just serotonin.

0:53:21.920 --> 0:53:25.760
<v Speaker 5>Add serotonin, yeh, sprinkle some serotonin.

0:53:25.239 --> 0:53:29.160
<v Speaker 4>Well, serotonin on top, this message didn't reach the general

0:53:29.200 --> 0:53:33.600
<v Speaker 4>public until I feel like, relatively recently, you've got again,

0:53:33.719 --> 0:53:37.560
<v Speaker 4>like popular media articles or TikTok saying things like you've

0:53:37.600 --> 0:53:40.560
<v Speaker 4>been lied to. Antidepressants don't do what we think, and

0:53:40.600 --> 0:53:45.760
<v Speaker 4>it's like yeah, or the final nail in the depression

0:53:45.800 --> 0:53:46.840
<v Speaker 4>serotonin coffin?

0:53:48.320 --> 0:53:49.280
<v Speaker 5>Is that a real headline?

0:53:49.320 --> 0:53:52.800
<v Speaker 4>Narin, I don't remember it, Okay, I think it actually,

0:53:53.000 --> 0:53:59.160
<v Speaker 4>I think it was because researchers again were like, final nail.

0:53:59.440 --> 0:54:02.200
<v Speaker 4>That thing's been dead for decades, it's been buried. What

0:54:02.200 --> 0:54:06.680
<v Speaker 4>are you talking about? But a few promoted or even

0:54:06.800 --> 0:54:12.000
<v Speaker 4>we're behind this misrepresentation of the science of SSRIs. You know,

0:54:12.080 --> 0:54:15.759
<v Speaker 4>this is where like this again the serotonin hypothesis as

0:54:15.800 --> 0:54:20.279
<v Speaker 4>the straw man argument against these medications, right, and this

0:54:20.680 --> 0:54:22.440
<v Speaker 4>I mean to go, I don't want to go too

0:54:22.520 --> 0:54:27.480
<v Speaker 4>much into like the motivations or the reasons for this misrepresentation,

0:54:27.600 --> 0:54:29.760
<v Speaker 4>because I do think that there is like an anti

0:54:29.840 --> 0:54:33.279
<v Speaker 4>psychiatry movement that you don't need drugs, You just need

0:54:33.320 --> 0:54:36.680
<v Speaker 4>to pull yourself up by the bootstraps, bootstraps and work hard.

0:54:36.760 --> 0:54:38.799
<v Speaker 4>Just get out of bed, clean your house, just do it,

0:54:38.880 --> 0:54:39.480
<v Speaker 4>just push.

0:54:39.560 --> 0:54:42.000
<v Speaker 5>Do it, just do it, right. I mean, that's the

0:54:42.000 --> 0:54:45.359
<v Speaker 5>same thing as before anyone recognized that depression was a thing, Right,

0:54:45.560 --> 0:54:48.440
<v Speaker 5>It's the same, that's the same end result.

0:54:48.280 --> 0:54:49.320
<v Speaker 3>It's the same end result.

0:54:49.600 --> 0:54:54.799
<v Speaker 4>The thing is this, this misrepresentation saying that scientists think

0:54:54.960 --> 0:54:59.320
<v Speaker 4>that SSRIs work on depression in this way and they're wrong.

0:55:00.160 --> 0:55:03.680
<v Speaker 4>That has the capacity to do real damage.

0:55:04.080 --> 0:55:07.320
<v Speaker 5>Especially to people who are on SSRIs, who have benefited

0:55:07.320 --> 0:55:12.680
<v Speaker 5>from SSRIs, who are now in charge of regulating our SSRIs.

0:55:12.400 --> 0:55:16.799
<v Speaker 4>It has or could encourage people to stop treatment under

0:55:16.840 --> 0:55:21.160
<v Speaker 4>these false pretenses. And it also just overall deepens mistrust

0:55:21.200 --> 0:55:24.800
<v Speaker 4>in science and medicine. The truth is that the general

0:55:24.840 --> 0:55:28.359
<v Speaker 4>public has been lied to, or at least not been

0:55:28.400 --> 0:55:34.319
<v Speaker 4>told the whole truth about our understanding of SSRIs and depression. Ads,

0:55:34.680 --> 0:55:37.880
<v Speaker 4>like pharmaceutical ads, which should be outlawed in my opinion,

0:55:38.960 --> 0:55:43.120
<v Speaker 4>for antidepressants, have long claimed that the drugs work by

0:55:43.160 --> 0:55:49.000
<v Speaker 4>correcting a chemical imbalance, and these ads reduce these complicated

0:55:49.000 --> 0:55:53.000
<v Speaker 4>disorders to a simple issue of brain chemistry. It's a

0:55:53.040 --> 0:55:55.560
<v Speaker 4>catchy thing. You got, you know, thirty seconds for an ad.

0:55:56.000 --> 0:55:59.240
<v Speaker 4>Of course you're going to say the simplest thing possible.

0:55:59.320 --> 0:56:01.759
<v Speaker 4>And what company wants to be like, we don't know.

0:56:01.640 --> 0:56:02.400
<v Speaker 3>How this works.

0:56:03.280 --> 0:56:05.160
<v Speaker 4>Of course they're going to say something like it's a

0:56:05.200 --> 0:56:10.880
<v Speaker 4>chemical imbalance. But I think that that under represents or

0:56:11.000 --> 0:56:14.000
<v Speaker 4>falsely represents the complexity of the issue and how much

0:56:14.040 --> 0:56:16.600
<v Speaker 4>we know or don't know about this. And I think

0:56:16.640 --> 0:56:20.680
<v Speaker 4>this trickles down into physicians who will use the same

0:56:20.760 --> 0:56:24.319
<v Speaker 4>language when explaining the medications to their patients. Again, not

0:56:24.360 --> 0:56:27.000
<v Speaker 4>wanting to sit there in an office, you have five

0:56:27.040 --> 0:56:29.440
<v Speaker 4>minutes to talk to your patient, and you don't want

0:56:29.480 --> 0:56:30.759
<v Speaker 4>to say we don't know how this works.

0:56:30.840 --> 0:56:31.279
<v Speaker 3>Number one.

0:56:31.480 --> 0:56:36.200
<v Speaker 4>Number two, let me tell you about how serotonin receptors

0:56:36.239 --> 0:56:37.280
<v Speaker 4>work in your brain.

0:56:37.120 --> 0:56:40.400
<v Speaker 3>And your gut. Right, I know. So it's laughing chemistry.

0:56:40.480 --> 0:56:41.319
<v Speaker 3>It's an imbalance.

0:56:41.560 --> 0:56:44.840
<v Speaker 5>I'm laughing so much erin because I it's my favorite

0:56:44.840 --> 0:56:47.480
<v Speaker 5>thing when I get to explain mechanisms to my patients.

0:56:47.480 --> 0:56:49.640
<v Speaker 5>So you're in the office or you get to be like, Okay,

0:56:49.640 --> 0:56:52.719
<v Speaker 5>this is too detailed, but just give me one and

0:56:52.760 --> 0:56:54.160
<v Speaker 5>then and then at the end be like, yes, so

0:56:54.200 --> 0:56:55.479
<v Speaker 5>we don't know how it works, but.

0:56:55.880 --> 0:56:58.480
<v Speaker 3>Right, but it's yeah, but no, but most people.

0:56:58.200 --> 0:57:01.040
<v Speaker 5>Don't do that. Yeah, yeah, most people. We also don't

0:57:01.040 --> 0:57:03.400
<v Speaker 5>do that, and like, yeah, okay, we learned the mechanism

0:57:03.560 --> 0:57:07.480
<v Speaker 5>in med school and then you obviously forget it because

0:57:07.680 --> 0:57:10.520
<v Speaker 5>there is way too much to know. And what you

0:57:10.600 --> 0:57:13.480
<v Speaker 5>really need to know is do I have something that

0:57:13.520 --> 0:57:16.880
<v Speaker 5>can help my patient or not? Right exactly so.

0:57:17.160 --> 0:57:19.280
<v Speaker 3>And I think that, like you know, I was thinking.

0:57:19.280 --> 0:57:21.920
<v Speaker 4>I just I've spent so much time thinking about SSRIs,

0:57:22.160 --> 0:57:25.160
<v Speaker 4>like in a very focused, directed way where I'm like, okay,

0:57:25.240 --> 0:57:29.400
<v Speaker 4>this these ads for example, or this message I'll say,

0:57:29.440 --> 0:57:31.920
<v Speaker 4>whether it's in an ad or in your doctor's office

0:57:32.000 --> 0:57:36.000
<v Speaker 4>or wherever, about depression and other mental health disorders being

0:57:36.040 --> 0:57:40.440
<v Speaker 4>a result of an imbalance in your brain chemistry. That

0:57:40.520 --> 0:57:44.680
<v Speaker 4>message has been really important for reducing stigma and for

0:57:44.800 --> 0:57:48.480
<v Speaker 4>underscoring the idea that these disorders are real and that

0:57:48.600 --> 0:57:54.360
<v Speaker 4>they can be treated with medical solutions. But by framing

0:57:54.440 --> 0:57:58.320
<v Speaker 4>it in this unnuanced way, by not acknowledging that there

0:57:58.360 --> 0:58:02.440
<v Speaker 4>are still unknowns, it ignores the need for more research

0:58:02.680 --> 0:58:06.000
<v Speaker 4>both on SSRIs as well as depression and other mental

0:58:06.040 --> 0:58:10.640
<v Speaker 4>health disorders. It disregards the experiences of many people for

0:58:10.680 --> 0:58:15.160
<v Speaker 4>whom these medications don't work, and it minimizes the importance

0:58:15.200 --> 0:58:19.080
<v Speaker 4>of non pharmaceutical interventions such as therapy. And it does

0:58:19.120 --> 0:58:23.320
<v Speaker 4>a disservice to everyone who uses, prescribes, or researches these

0:58:23.360 --> 0:58:27.320
<v Speaker 4>medications or alternative treatments for depression and other mental health disorders.

0:58:28.640 --> 0:58:32.480
<v Speaker 4>There is no question that in the decades since Prozac's release,

0:58:32.840 --> 0:58:37.000
<v Speaker 4>SSRIs have completely changed the landscape of depression. They have

0:58:37.080 --> 0:58:40.320
<v Speaker 4>provided relief to so many people. They've been a life

0:58:40.320 --> 0:58:43.440
<v Speaker 4>saving to so many people. They have helped to reduce

0:58:43.480 --> 0:58:47.480
<v Speaker 4>stigma surrounding depression and other mental health disorders. They have

0:58:47.600 --> 0:58:50.560
<v Speaker 4>forced us to reconsider how we think of mental illness.

0:58:51.320 --> 0:58:55.240
<v Speaker 4>They are not perfect, but I don't know anyone who

0:58:55.280 --> 0:58:59.400
<v Speaker 4>claims they are, besides maybe the pharmaceutical companies.

0:58:59.160 --> 0:59:02.680
<v Speaker 5>Don't know any neat drug that is perfect.

0:59:02.760 --> 0:59:03.840
<v Speaker 3>No drug, you're perfect.

0:59:04.120 --> 0:59:10.360
<v Speaker 4>Yeah, But I'm I'm excited though for next week, Arin,

0:59:10.720 --> 0:59:13.320
<v Speaker 4>when you get to tell me about more about how

0:59:13.400 --> 0:59:15.920
<v Speaker 4>much we don't know and how much we do know

0:59:16.200 --> 0:59:19.480
<v Speaker 4>about these medications and how we can make them maybe

0:59:19.560 --> 0:59:21.360
<v Speaker 4>not perfect but better.

0:59:22.160 --> 0:59:24.920
<v Speaker 5>Hmmm, that's a good one. I probably won't answer that question,

0:59:24.960 --> 0:59:28.480
<v Speaker 5>but I will provide quite a lot of data to

0:59:28.600 --> 0:59:31.560
<v Speaker 5>support what we do and don't know. And then a

0:59:31.600 --> 0:59:33.439
<v Speaker 5>little bit in my opinions about how we talk about

0:59:33.440 --> 0:59:34.120
<v Speaker 5>all of this too.

0:59:34.160 --> 0:59:34.960
<v Speaker 3>Oh love it?

0:59:35.000 --> 0:59:39.640
<v Speaker 5>Okay, next week more next subscribe so that you don't

0:59:39.640 --> 0:59:40.120
<v Speaker 5>miss an.

0:59:40.040 --> 0:59:45.200
<v Speaker 4>Episode, never miss an EPP. And in the meantime, how

0:59:45.200 --> 0:59:45.920
<v Speaker 4>about some reading?

0:59:46.200 --> 0:59:49.320
<v Speaker 5>How about some reading? I'd love to do more reading, Aaron.

0:59:51.280 --> 0:59:53.160
<v Speaker 4>I have a bunch of sources, but I'm going to

0:59:53.200 --> 0:59:58.040
<v Speaker 4>shout out three in particular. There's by Whittaker as Media

0:59:58.280 --> 1:00:00.880
<v Speaker 4>in nineteen ninety nine, The Discovery of serotonin and its

1:00:00.960 --> 1:00:04.880
<v Speaker 4>role in neuroscience from Hillhouse and Porter twenty fifteen, A

1:00:04.920 --> 1:00:08.160
<v Speaker 4>brief history of the development of interdepressant drugs from Monoa

1:00:08.200 --> 1:00:11.880
<v Speaker 4>means to glutamate, and then kind of just the broad scope,

1:00:12.280 --> 1:00:18.040
<v Speaker 4>big picture of depression and the advent of SSRIs and

1:00:18.080 --> 1:00:21.439
<v Speaker 4>how that changed the landscape. There was a couple great

1:00:21.520 --> 1:00:26.040
<v Speaker 4>chapters in a book called Mind Fixers Psychiatry's Troubled Search

1:00:26.080 --> 1:00:30.200
<v Speaker 4>for the Biology of Mental Illness by Anne Harrington, and

1:00:30.720 --> 1:00:32.040
<v Speaker 4>I've got more I'll post.

1:00:31.920 --> 1:00:32.760
<v Speaker 3>Them on our website.

1:00:32.760 --> 1:00:34.720
<v Speaker 4>This podcast will kill you dot Com.

1:00:35.200 --> 1:00:38.320
<v Speaker 5>Thank you again so much to the providers of our

1:00:38.320 --> 1:00:41.920
<v Speaker 5>first hand account. We appreciate you so so so much.

1:00:42.040 --> 1:00:44.120
<v Speaker 5>And thank you to everybody who wrote in to share

1:00:44.160 --> 1:00:46.920
<v Speaker 5>your story about SSRIs. We really appreciate it.

1:00:47.080 --> 1:00:48.200
<v Speaker 3>Yeah, thank you, Thank you.

1:00:48.920 --> 1:00:53.200
<v Speaker 4>Thank you also to Bloodmobile now on Instagram for the

1:00:53.320 --> 1:00:55.720
<v Speaker 4>music that you provide for this episode in all of

1:00:55.720 --> 1:00:56.480
<v Speaker 4>our episodes.

1:00:57.640 --> 1:01:01.960
<v Speaker 5>Thank you to Leanna and Tom and Brent and Pete

1:01:02.200 --> 1:01:07.480
<v Speaker 5>and Mike and Jess and everybody exactly right for all

1:01:07.480 --> 1:01:08.960
<v Speaker 5>your help making these episodes happen.

1:01:09.200 --> 1:01:12.200
<v Speaker 4>Yes, thank you, and thank you to you listeners and

1:01:12.360 --> 1:01:16.520
<v Speaker 4>watchers and anyone who partakes in the podcast in some way.

1:01:16.560 --> 1:01:19.800
<v Speaker 3>We really appreciate it that we do. Thank you. Thank you.

1:01:20.320 --> 1:01:23.080
<v Speaker 5>Thank you as always to to our patrons for your

1:01:23.160 --> 1:01:26.240
<v Speaker 5>support over on Patreon. We really really appreciate it. It means

1:01:26.280 --> 1:01:26.560
<v Speaker 5>a lot.

1:01:26.720 --> 1:01:27.600
<v Speaker 3>We do well.

1:01:28.400 --> 1:01:31.920
<v Speaker 5>Until next time, wash your hands, you filthy animals,