Episode Transcript
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Speaker 1 (00:00):
My name is Will and my experience with ssriyes and
esenriyes started when I was in pharmacy school. Actually, I
was diagnosed with both anxiety and depression at the same time,
which was a lot of fun, especially when I was
in a doctorate program and my doctor started me on
(00:21):
s a telegram on lexaprob. It worked fairly well for
a while, needed a little bit of help from buse
Peronne to get through the anxiety, but I did okay.
That said, I still had some breakthrough symptoms and I
especially had side effects. I had a lot of the
sexual dysfunction side effects, and I also gained about thirty pounds,
(00:43):
so I swapped off of that for a while when
I'm a little bit of a vacation, but then my
symptoms started coming back and getting worse. So I got
started on wellbutrin bupropion, and I did a lot better
symptom wise on it, but again I had really really
bad side effects. And it wasn't so much suicidal ideation
as it was just an acute knowledge of my own mortality,
(01:05):
which is not great when you had anxiety and depression.
So at that point I had the wherewithal because of
my education as a pharmacist to ask my doctor to
go on and do genetic testing, which I'm glad I
did because when we got the results back, it turned
out that there were only about two antidepressants and a
(01:25):
couple of anxiolytics that were on my green as go list.
That is to say, you know that my hepatic enzyme
is going to metabolize without giving me two bad side effects.
And that is kind of the journey of how I
found pristique des been the fact sine that is the
miracle drug that worked for me. But I still can't
help but wonder how long it would have taken me
(01:47):
to find my miracle drug if we did it kind
of the old fashioned way. If I hadn't known to
ask for this genetic testing, I could have been trying
and failing SSRIs and SNRIs for years, years before I
found the drug that worked for me. So you know,
I try and advocate for the genetic testing and for
(02:07):
being your own advocate as a patient whenever I can,
because I just I know that there are a ton
of people that don't have the same sort of background
as I had the good fortune of having. So as
a fellow health professional, I definitely tell patients all the time,
make sure you're advocating for yourself, even if it's just
(02:29):
asking questions.
Speaker 2 (02:33):
Taking SSRIs is the best thing I've ever done. I've
always had trouble with OCD in terminal anxiety from a
young age, probably as long as I can remember. I
would have like a baseline level of anxiety and OCD,
and then every so often I'd have these periods where
it got so much worse and it was all consuming.
(02:53):
I spent all my time in my own head, worrying, ruminate,
in doom, mental compulsions. I struggled to eat, or sleep
or socialize, and it really started to have an effect
on my personal life. I managed to get through work
and other commitments without most people noticing, but I wasn't
present and it was really horrible to endure. I felt
(03:13):
like I didn't deserve anything nice or for my family
to be even sympathetic to me because of these awful,
intrusive thoughts I was having. These periods were so difficult
that when they subsided, I was so grateful that I
didn't even notice the baseline level of anxiety I had
all the time, and how much of an impact that
was having on my life. Last October, I had an
(03:33):
OCD flare up, and it was the worst it's ever been.
I was in a really dark place. My therapist recommended
taking fla woxatine, and I was so desperate to feel
better I would have taken anything. Within a few weeks,
I started to feel more myself again. The thoughts quietened,
and I remember getting really emotional because it was so
strange for me to feel like that, my mind being
(03:56):
quiet for once. I can't emphasize enough how much of
a sitive impact they've had on my life. It was
the first time in my life I'd actually felt content
in myself and excited for the future. I'm so much
happier now and just enjoying life to the fun. I'm
so grateful that I don't have to feel that permanent
level of anxiety and intrusive thoughts anymore.
Speaker 3 (04:18):
I've literally never felt.
Speaker 2 (04:19):
Like this in my life before, and it really hammered
home how much I'd been struggling on a daily basis
and didn't even notice. The tablets alongside the therapy were
like a helping hand to pull me out of a
really dark hole. My only regret is not taking them.
Any sooner.
Speaker 4 (05:22):
Thank you so much for providing your first hand account.
That really means it means so much. I know we
say it all the time, but it always does. It
really does.
Speaker 5 (05:30):
It means so much every single time, honestly, So thank you,
and thank you to everyone who wrote in. We really
really do appreciate it.
Speaker 3 (05:37):
We do.
Speaker 5 (05:38):
Hi.
Speaker 3 (05:39):
I'm Aaron Welsh.
Speaker 5 (05:40):
And I'm Erin Alman Updike and this is this podcast
will kill You. And today we're talking about SSRIs.
Speaker 4 (05:47):
About SSRIs, and next week we're talking about SSRSR. Yeah,
I mean, it really does warrant at least two full episodes,
Like there's so much there in the history, in the
biology and sort of the current the discourse.
Speaker 3 (06:09):
James, we did not plan that, No, we did. That's thrilling.
Just shows that we're best friends.
Speaker 5 (06:15):
Like yeah, and we spent way too much time like
thinking about this too and with each other.
Speaker 3 (06:21):
Yeah yeah, yeah.
Speaker 5 (06:23):
But yeah, So we're gonna do a two parter this week.
Aaron Welsh's gonna tell me all about the history because
I don't know it other than like we had MAOIs
and then TCAs and now SSRI's what I've done. Next
episode and then next week, I'll get into what we
think we know about how SSRIs actually work and their mechanism,
(06:47):
and then yeah, I'm excited to tell you what I know,
and then some of the yeah, the current discourse.
Speaker 3 (06:55):
Current.
Speaker 4 (06:58):
But before we get into all all of that, it
is of course quarantine.
Speaker 5 (07:02):
Quarantin any time or should we say plusy berrita time.
Speaker 4 (07:06):
This week we've been like mixing it up and every
now and then it's like, what do you what do
you feel like doing plasy parita This week we'll do
this one. Yeah, this week is the serotonin sprits.
Speaker 5 (07:17):
Couldn't be anything else. It could have been Actually we
thought about other things.
Speaker 4 (07:22):
We were like, this is as bad as it is.
It's the best we can do.
Speaker 3 (07:27):
Saraton sprits. It's pretty simple.
Speaker 4 (07:29):
It's it's got soda water, hence the sprits. It's got
sparkling apple cider and some pineapple juice. And it's tasty.
It's simple, it's refreshing.
Speaker 5 (07:39):
Yeah, for a warm or a cold day.
Speaker 4 (07:44):
Yeah, sure, jack of all trades anyway.
Speaker 5 (07:48):
The full recipe on our website, this podcast with kill
you dot com and our socials. Are you following us there?
Because you could and should be. We're on Instagram, TikTok,
the Facebook, loose Sky. We're also online on a website
called This Podcast Will Kill You dot com. Have you
checked it out yet, because if you haven't, what a
wealth of things you'll find there.
Speaker 3 (08:09):
So many things.
Speaker 5 (08:10):
The bookshop dot org affiliate list account that we have.
You're doing you're doing it, thank you, good reads list, transcripts,
We've got Bloodmobile. We've got sources from every single one
of our episodes, including this one.
Speaker 3 (08:27):
What else is now on Instagram?
Speaker 5 (08:29):
So oh really that's exciting.
Speaker 3 (08:32):
Check them out.
Speaker 5 (08:33):
Check we've got merch We've got a link to our
Patreon account. If you haven't yet dropped a what do
you call it? Rate and review and subscribe. I'm trying
to do too much.
Speaker 3 (08:47):
Be sure to do that. Do it?
Speaker 5 (08:49):
Okay, we're on YouTube.
Speaker 1 (08:51):
There we go.
Speaker 3 (08:53):
Let's just try to take a little off your plate.
Thank you.
Speaker 5 (08:56):
My plate is done.
Speaker 4 (08:57):
The end, the end, and the beginning. Let's take a
quick break and get started.
Speaker 5 (09:04):
I can't wait.
Speaker 4 (09:22):
In December nineteen eighty seven, the FDA approved Prozac for
treatment of depression, and it became the first ssri to
hit the US market. The following January within two years,
pharmacies were filing one million prescriptions each month.
Speaker 5 (09:41):
Wow in the US.
Speaker 3 (09:44):
In the US Wow.
Speaker 4 (09:46):
Today, global numbers are hard to pin down. I'm sure
you'll do some Aaron math maybe, but no, I won't. Sorry, well,
they're really hard to find. I mean, googled for like
five minutes and no, it was longer than that.
Speaker 5 (10:04):
Was I believe it was substantially longer than that.
Speaker 4 (10:09):
But I did find one estimate from the CDC from
twenty eighteen where they suggested that thirteen percent of people
in the US are on antidepressants, which comes out to
around forty two million people, and this is likely an
underestimate since prescriptions have increased in recent years. As antidepressant
use has grown, so has the controversy surrounding these medications.
(10:33):
RFK Junior, the Secretary of the US Department of Health
and Human Services, despite having zero medical training, has made
claims that SSRIs are more harmful and addictive than heroin,
so claims not supported by any data, and has proposed
limiting their use, instead sending people to quote unquote wellness farms. Yeah,
(10:59):
I mean we could do an entire Yeah.
Speaker 5 (11:02):
I'm sorry, it's just so unseerious, but it's very very serious.
He's very much in charge of everything right now. But
it's one of those you laugh or you just break
down and give up on everything.
Speaker 3 (11:14):
Is I laugh?
Speaker 4 (11:16):
I mean I'm scared every day and it feels surreal
every day.
Speaker 5 (11:20):
And yeah, yep, I mean.
Speaker 3 (11:22):
This is like.
Speaker 4 (11:23):
Wellness farms are not a new concept, and it's never
been a good concept. We could do an entire episode
in the dark history of wellness farms or the ones
similar to the ones that he presumably has in mind,
my guess, and how ablest and racist and sexist and
classist they are.
Speaker 5 (11:42):
It's dark. It's dark.
Speaker 3 (11:44):
It's dark.
Speaker 4 (11:45):
But this controversy extends beyond conspiracy theories and conspiracy theorists
like RFK Junior, with some psychiatrists and researchers expressing reservations
about the way that we use or think about antidepressants
and mental health disorders, prompting the popular media to release
articles exploring this controversy with headlines like the risks and
(12:08):
Rewards of antidepressants and do antidepressants work better than Placebo?
Speaker 3 (12:15):
Despite all the.
Speaker 4 (12:16):
Progress that has been made in raising awareness and being
open about mental illness, it is still a taboo subject
in many ways, very much so. Acknowledging that you struggle
and seeking help because of that is perceived by some
as or by many, as a weakness.
Speaker 3 (12:33):
Oh we all.
Speaker 4 (12:33):
Get a little blue here and there. You don't need meds.
Just think on the bright side, go get some fresh air,
just take a walk, take a nice little stroll. Or yeah,
I get anxious too. Sometimes I just try not to
think about it.
Speaker 3 (12:47):
Just kind of put it in a box, put it away.
Just stop.
Speaker 5 (12:53):
Yeah, just stop to stop. Just stop being anxious and depressed.
Speaker 3 (12:57):
That's easy, that's easy.
Speaker 4 (13:00):
The stigma surrounding mental health disorders also extends to the
treatments that people seek, whether that's an SSRI or therapy,
and the stigma, no doubt, contributes to the constant questioning
of antidepressants by the general public. However, the skepticism that
some researchers or healthcare practitioners express towards SSRIs, while likely
(13:25):
influenced by this overarching doubt, is also informed by the
gaps in our scientific knowledge about the causes of mental
illness and the mechanisms by which SSRIs may work to
improve symptoms. So, in other words, like what do these
medications do and how do they do it? And next week, Aaron,
(13:45):
I know that you're going to take us through the
long answers to these questions, but the short answer is
that we don't really know.
Speaker 5 (13:53):
Yeah, I mean, that's the conclusion of next week's episode.
Speaker 4 (13:56):
Yeah, yeah, yeah, I mean we have some ideas, and
those ideas have changed over the decades, but we don't
know for certain how these medications work. And that's partly
because we don't understand the underpinnings of depression, of anxiety,
of obsessive compulsive disorder, and of other mental health disorders. Yeah,
(14:17):
and at first glance that maybe that sounds a little strange,
like what do you mean we use these antidepressants but
we don't quite know how they work.
Speaker 5 (14:26):
It doesn't sound strange if you work in medicine.
Speaker 4 (14:27):
Aaron I was gonna say, there are still there's so
many medications that are also mysterious. There's acetaminifin paracetamol. We
don't know why or how it reduces pain and fever.
Met Foreman is still a bit of a black box.
Even a few of our general anesthetics holds some mystery.
Speaker 5 (14:43):
There is probably more medicines that we do not fully understand.
And I don't just mean like how they work, like
a lot of things we know, like it binds to
this receptor and this mechanism happens. That does not mean
that we understand how like why do they improve the
thing that they improve, because we use a lot of
medicines for a whole bunch of different stuff, Like I'm
(15:05):
going to get into it next week more as well too,
like this concept and the way that we talk about
these medicines for depression versus other medicines that we don't understand.
But yeah, it's it is not just SSRIs.
Speaker 3 (15:18):
It's not it's not.
Speaker 4 (15:19):
And I think that this speaks to how our approach
to drug development is not always guided by a find
the specific problem, engineer the targeted solution mindset, Like that's
just not the way that drug development often works, and
maybe maybe that's the ideal way, but like that rarely
rarely happens, or it doesn't happen, and we think that
(15:41):
we've found the solution, but it's like, well, we didn't
quite understand the problem in the first place.
Speaker 5 (15:46):
That's the thing. You have to know the problem very
clearly to be able to do that kind of targeted development.
So we have that for some situations, right, for some cancers,
for example, Yes, but not for a lot of other
disorder that are more nebulous, that have multiple factors that
contribute to their development. Right.
Speaker 4 (16:05):
I mean it's kind of it's kind of amazing, like
and just just how much serendipity can play a huge
role in bridging these gaps of like, we here's this problem.
Speaker 3 (16:18):
What's the solution? Right?
Speaker 4 (16:20):
We don't have the information, But then something comes along
and it's like, hey, that seems to work.
Speaker 5 (16:26):
How does it work? How does We'll figure that out
later right now? Yeah, it's what is it doing first?
And then how does it work? How does it We
don't have the how does it work for a lot
of things?
Speaker 3 (16:37):
Yes? Yeah?
Speaker 4 (16:38):
And so what I want to do in this episode
is take us through the story of SSRIs, starting with
serotonin itself and how the first antidepressants were developed, and
then ultimately ending with kind of a small reflection of
how these medications have led a revolution in our understanding
and perception of mental illness. That's the good, the bad,
(17:00):
and everything in between.
Speaker 5 (17:01):
I can't wait.
Speaker 4 (17:02):
So let's start at the beginning with serotonin. The neurotransmitter
and cellular messenger. That's the star of this episode.
Speaker 5 (17:11):
I can't wait.
Speaker 3 (17:13):
Which to do.
Speaker 4 (17:15):
This means that we have to start pretty far back, Okay,
billions of years back.
Speaker 3 (17:21):
You know.
Speaker 5 (17:21):
I love it when you go deep time a time.
Speaker 4 (17:23):
I mean, I'm not going to stay deep for very long,
but it's okay, it is.
Speaker 3 (17:28):
I was so.
Speaker 4 (17:28):
Surprised to learn how ancient serotonin serotonin, I mean two
to three billion years ago.
Speaker 5 (17:37):
Wow.
Speaker 4 (17:37):
It can basically be found in all walks of life,
from bacteria to protozoans, leeches, worms, fishes, birds, plants. Did
you know that plants make serotonin?
Speaker 5 (17:47):
No? But that makes me so happy.
Speaker 3 (17:49):
I know why I don't know dogs humans?
Speaker 4 (17:53):
I mean basically yeah, I mean dogs make sense. Plants
is a little more like it's a little what so
basically everything. It exists in all the organs of the
human body, which is pretty fascinating, but not as fascinating
as the fact that it's found in basically every living
organism on this planet.
Speaker 3 (18:12):
Wow, So what does this tell us?
Speaker 4 (18:15):
Like, it's so widespread and so ancient that it means
that a this serotonin is got to be really important,
super important, and be just how many ways. It is important,
like the varied roles that it can play.
Speaker 5 (18:30):
It's obviously not just doing one thing exactly.
Speaker 4 (18:33):
It's not just oh, this is the depression neurotransmitter in
humans only, right, Yeah, I mean, and we tend to
think of and describe serotonin as a neurotransmitter, which it is,
but it also existed before neurons did.
Speaker 5 (18:49):
Oh my gosh, stop.
Speaker 3 (18:51):
Isn't that wild?
Speaker 5 (18:52):
Well, yeah, because if you're talking about bacteria have serotonin,
I didn't know that. Yeah, yeah, you don't have neurons exactly,
You're just one cell.
Speaker 4 (19:02):
This neurotransmitter existed before it could be transmitted by neurons.
Speaker 3 (19:06):
Like, what is so cool? It's so cool?
Speaker 5 (19:10):
Do we know what that does in bacteria?
Speaker 4 (19:13):
I'm watching a lot of it is like energy capture
or regulation or management. Sometimes there's like intracellular or like
a signaling between.
Speaker 5 (19:23):
Different still signal what it is for us? Okay, okay, yeah, yeah.
Speaker 3 (19:28):
I mean it is involved.
Speaker 4 (19:29):
Like these are just some of the things that it's
involved in just across life, which is regulating cell activity
and signaling. Development and plasticity plays a huge role generation,
energy consumption, metamorphosis, embryogenesis, digestion, feeding behaviors, motor activities, sleep regulation,
(19:49):
neurological development, decision making, stress responses, mood behavior, social dynamics, anxiety, learning,
and memory, just to name a few, just a few.
It's everywhere does everything. Yeah, and so Aarin, I know
that next week you'll tell us more about what seratonin's
role is thought to be in humans, or like at
least some of the things that we know it does, right,
(20:12):
But I wanted to share just a couple of fun
tidbits that I discovered in researching for this. I can't
not on the non human side of things. Okay, So
we love leeches, we do, and we.
Speaker 3 (20:24):
Love kissing bugs.
Speaker 4 (20:25):
Is love is not the right word, But we are
intrigued by kissing gigs.
Speaker 5 (20:29):
Appreciate their They are interesting.
Speaker 4 (20:31):
Creatures, yes, and we have episodes that feature both of
these creatures. In these two In medicinal leeches and kissing bugs,
serotonin acts as a signal to expand their stomach so
that they can eat many, many, many more times their
body size blood.
Speaker 5 (20:47):
It's what, lets just suck all of our blood.
Speaker 4 (20:50):
Yep yep, just expand expand. It also seems to help
leeches swim.
Speaker 5 (20:55):
Oh.
Speaker 4 (20:56):
In some species of worms, it stimulates development and egg laying.
In certain marine molluscs, environmental serotonin is needed to induce
metamorphosis from the larval to the adult stage, and so
it's thought that the serotonin is produced by algae which
the mollusks feed on. And so if you are detecting
(21:17):
not high enough levels of serotonin and you're a mollusk
and you're like, wait, where's the serotonin the environment and
it's a little low, that could signal a resource poor area.
So it's like, don't metamorphose here, you won't get enough
to eat. What serotonin?
Speaker 5 (21:31):
Serotonin?
Speaker 4 (21:33):
It's incredible, I mean, and we could spend forever talking
about what serotonin does in different species or tissues or organs.
But do you know what else is fascinating about serotonin?
I want to how it was discovered, Okay, okay. I
was surprised that how much serotonin history. I was like, okay,
I got to start at the beginning. What's the story
(21:55):
of serotonin?
Speaker 5 (21:57):
Right?
Speaker 4 (21:57):
And then I was like, actually, this is fascinating. But
I've thought about serotonin in isolation, like I've always thought
about it in the context of SSRIs or in mental
health disorders and like, what does it do in humans?
Without thinking of it? It's a broader picture. Yeah, yeah, okay,
So serotonin discovery. The early decades of the twentieth century
(22:18):
were an exciting time to be a molecular biologist because
what they found was that these increasingly sensitive bioassays allowed
them to tease apart the functions of the tiny compounds
that are constantly flitting around within the bodies of animals,
humans and other animals, things like hormones or antibodies, vitamins,
(22:41):
and of course neurotransmitters. What do these different molecules do,
how do they interact with one another, what happens if
things go awry? And how can we use all this
knowledge to develop medications to treat certain conditions. These were
the types of questions that motivated many researchers in the
(23:02):
nineteen thirties, among them an Italian physiologist and pharmacologist named
Vittorio or Spammer.
Speaker 3 (23:09):
We'll try that.
Speaker 4 (23:10):
I say his name a bunch more times, so great,
but Erspimer had a particular interest in deriving pharmacologically active
substances from nature to use in medications because he so
he would be like, what is this plant alkaloid. Can
we use this as a medication? What does it do
these sorts of things? Okay, it was a very hot
(23:30):
time for that. If you think also of things like
willow and aspirin, and you think of quinine malaria, that's
sort of right anyway.
Speaker 3 (23:40):
So his work.
Speaker 4 (23:41):
Erspimer's work centered around the smooth muscle of animals and
trying to figure out which substances caused it to constrict
or contract. So he looked at the skins and intestines
of rabbits, of molluks, of molluscs it's a hard word
to say, and of frogs to name a few, and
substance found in a certain type of cells in the
(24:03):
gut caught his eye. When he isolated it and tested
it out. He observed that it caused smooth muscle contraction,
and it didn't seem to be any of the recently
discovered usual suspects. It was something completely undescribed at that point,
and so he named it enteramine in his nineteen thirty
seven paper.
Speaker 5 (24:22):
Okay.
Speaker 4 (24:24):
In the subsequent years, he found the substance in many
other organisms and tissues, mollus cart octopus, salivary glands like
I guess had a particular bent towards ocean creatures. Yeah, creatures,
and he seemed quite enamored with it. In a letter
that he wrote at eighty nine years old, so way
(24:44):
way later, he described it as quote unquote my firstborn daughter, Okay,
really loved enter remine.
Speaker 3 (24:52):
Yeah.
Speaker 4 (24:53):
But where Erstimer was actively looking for this stuff, another
research group which was comprised of researchers Maurice, Rapport, Arta Green,
and Irvine Page, they were looking for how to get
rid of it. So since nineteen forty eight they had
been investigating the cause of hypertension in the hopes of
(25:16):
developing a drug and kept coming across the substance in
their clotted blood samples, where it seemed to act as
a vasoconstrictor interesting erin. Yeah, and so they were like, gosh,
this is like one collaborator later said, Yeah, the group
just kind of thought of it as a contaminant, and
they were like, how can we identify this so that
(25:36):
we can get rid of it, get rid of it
out of our samples, I mean, And that might be
underestimating their interest or understating their interest, because they ended
up isolating, synthesizing and then producing an elemental analysis of
the serum vasoconstrictor, which they named seratonin in nineteen forty eight,
(25:56):
not knowing that it already had a name.
Speaker 5 (25:58):
Right, Yeah, they went out.
Speaker 4 (26:01):
They yeah, they won out. I mean, and I think
they won out because it was the serum part. The
pharmaceutical company liked the name sarah like SCR to indicate
that it was found in the serum.
Speaker 3 (26:14):
I don't know first they named it.
Speaker 4 (26:16):
Yeah, five hydroxy trip trip to mean. But the pharmaceutical company, yeah,
they were like serotonin.
Speaker 5 (26:22):
I mean, that is still what it is called. It's
like five hydrox yeah, five h yeah yeah, five ht yes.
Speaker 4 (26:29):
But they yeah, they wanted a catchier which I appreciate.
I five hydroxy trip to mean is a hard is
a harder one to say, for sure. But within a
few years this research group realized that, oh wait a second,
this thing already like has been described, and so enter
I mean and serotonin actually the same thing. And then
they published this in a paper saying like, hey, these
(26:52):
these two things are the same. And this kind of
like expanded the interest and sort of the knowledge base
of what this thing does. Right, But at the time
it was still thought of as primarily a vasoconstrictor and
involved in smooth muscle contraction. Its role as a neurotransmitter
had not yet been uncovered, and when it was, it
(27:16):
would launch serotonin out of the realm of like cool
physiological things like this is neat, maybe this does something
in mollusks and into the burgeoning field of brain chemistry.
(27:43):
There was a researcher named Betty Tuurog who had been
interested in understanding a phenomenon in the muscles of muscles. Okay, yeah,
the organized the vibe out and she had identified serotonin
as a likely candidate for were the mystery neurotransmitter that
that she had suspected of playing a role. The structures
(28:05):
seemed to match, and analyzes confirmed her hypothesis, making serotonin
a neurotransmitter. But this landmark finding had trouble getting published
because the editor of the journal that she submitted to
sat on it for two years because he was like,
this is not worthy of review two years, and he
(28:25):
only sent it out for review after her advisor was like, hey, man, like,
what's the deal.
Speaker 3 (28:30):
Can you please review this? This might be a.
Speaker 4 (28:32):
Pretty huge finding. Yeah, And it was. It didn't get
a ton of traction. It's funny because it came out
I think after another paper that got a lot more traction,
which makes sense. But anyway, so TWAA didn't stop there
with just this like this is a neurotransmitter. She reasoned
that if saratonin was an important neurotransmitter in invertebrates like muscles,
(28:55):
it was probably invertebrates too. One of her advisors was like,
I don't so, I think this is just a this
is just just an invert thing. Yeah, just an invert thing,
just like a very you know, like primitive transmitter of course, right, Yeah,
but she got the last laugh because she isolated serotonin
(29:15):
not only from muscle nervous tissue like in the bivalve,
but from mammalian brain as well, and her resulting nineteen
fifty three publications started a new chapter or even a
new book really on serotonin in brain function and mental illness.
Speaker 5 (29:33):
Fascinating.
Speaker 4 (29:34):
So that is how serotonin was like discovered and then
discovered to be a neurotransmitter in the mammalian brain.
Speaker 5 (29:44):
Something that was in the mammalian brain that potentially was
having effects. Yes, in the mammalian brain.
Speaker 3 (29:49):
What do we do with this?
Speaker 5 (29:50):
Yeah?
Speaker 4 (29:50):
So since the nineteen forties, LSD fascinated those who knew
about it, of course that dead who also wondered at
its psychedelic properties. So a couple of these researchers, Dilworth
Woolley and Elliott Shaw followed these developments on serotonin with
great interest because the neurotransmitter was structurally very similar to LSD.
(30:15):
So when they like, when that chemical structure was published
by that first group, they were like, this is this
is really interesting and they thought, Okay, maybe because it's
so structurally similar to LSD, does this mean that LSD
could act as a block, like fitting into serotonin's receptors
(30:36):
and preventing it from working. Okay, And this concept of
like a lock and key for neurotransmitters would form the
basis for understanding how drugs could act as either mimicking
a natural substance like a neurotransmitter or a hormone, or
blocking its action like LSD did to serotonin. So it
(30:56):
was like, what does this do? Can this either flood
brain with more of the same and then there are
all the receptors are filled in the way that it
normally and things continued to act the way they would,
but maybe like kind of elevated elevated or would it
block block the action exactly? Yeah, And so sure enough,
(31:17):
when it came to LSD, that is exactly what happened
when someone tried it out. It blocked serotonin and so
receptors receptors, and so for Woolley and Shaw, this raised
the question of whether serotonin could play a role in
mental illness because they had observed that people who were
on LSD could experience mental disturbances that looked very similar
(31:40):
to something like schizophrenia, for example, And so what if
those disturbances were the results of the drug blocking serotonin.
So maybe, to extend this even further, they thought, Okay,
maybe it's not just about someone on LSD and these disturbances,
but what if mental illnesses, mental health disorders like schizophrenia,
(32:02):
are actually some sort of mismatch or decrease in serotonin serotonin. Yeah,
And so subsequent experiments and closer scrutiny in this idea
showed that it didn't quite work out that way, particularly
when it came to schizophrenia, But there was something to
the idea, and researchers began testing other drugs that could
(32:26):
either deplete or replenish stores of serotonin.
Speaker 5 (32:29):
Okay.
Speaker 4 (32:30):
One of these serotonin depleters was recurpene.
Speaker 3 (32:34):
Does this sound familiar? Yeah?
Speaker 5 (32:36):
Okay, did we talk about it on the podcast or
you the podcast?
Speaker 3 (32:40):
Yeah?
Speaker 4 (32:41):
Because I was like, this sounds familiar, So I did
a control f of our transcripts.
Speaker 3 (32:46):
Sure enough, and yeah.
Speaker 4 (32:48):
So recurping is an alkaloid from the snake wood plant
Rau Wolfia serpentina, and it was examined as a possible
treatment for hypertension. And then but this is not this
is not when we I'll tell you about it in
a second, okay, Okay, Okay, First I'm going to get
to like the serotonin part. So researchers found that people
(33:10):
were given recurping, uh, and then they tended to become depressed,
which was resolved if treatment stopped. So they were like,
what is recurping doing that is causing these symptoms of depression?
And it seems very clearly resurping because it stops with
stopping the treatment.
Speaker 3 (33:28):
Stopping treatment.
Speaker 4 (33:29):
Yeah okay, And so in tests carried out on rabbits,
resurping was found not only two deplete stores of serotonin,
which was a big contender, but also nouropinephrin, and a
newly discovered neurotransmitter called dopamine.
Speaker 5 (33:44):
Dopamine.
Speaker 4 (33:45):
Yes, so we talked about this in our Parkinson's arkansans.
This is how el dopa was found because they they
found that when you when you gave rabbits high doses
of recurping, they tended to exhibit some of like paraals symptoms.
Speaker 5 (34:00):
Similar to Parkins.
Speaker 4 (34:03):
And then they added el dopa and that sort of
snapped them out of it, ultimately meaning the researchers to
discover dopamine.
Speaker 3 (34:09):
Wow.
Speaker 4 (34:09):
Okay, but what does this all mean for depression and
under and other mental health disorders? Like talked about Parkinson's,
I've talked about hypertension, I've talked about schizophrenia. We haven't
really talked about depression yet. Okay, the precise mechanism wasn't clear,
but researchers hypothesized that maybe it was depletion of serotonin, dopamine,
(34:31):
and nouropinephrine that underlay the development of depression, and that
accesses might also lead to psychosis, especially when it came
to dopamine. So, in other words, mental illness might be
a result not of psychological imbalances, but rather chemical ones.
And so this is really when like the imbalance sort
(34:55):
of notion of mental health illnesses began.
Speaker 5 (34:59):
And specific imbalances of those three like monozines.
Speaker 4 (35:02):
Yeah, the monoamine or catacholamine hypothesis of depression was essentially
born out of these experiments.
Speaker 5 (35:09):
Okay, okay, yeah, okay.
Speaker 4 (35:11):
So I want to take a second here to ground
ourselves in what depression meant. At the time this research
was happening, this is the nineteen fifties, nineteen sixties or so,
it was rarely diagnosed. It wasn't often even included as
a separate category of diagnosis. Like there was really like
depression as a diagnosis. When patients expressed symptoms that today
(35:36):
we would associate with depression, so despondent, low energy, chronically sad,
something that would interfere with their everyday life, they were
usually ascribed to an expression of someone's anxiety, so like
anxiety was thought to be at the heart of most
mental health disorders at the time, some clinicians felt that
depressive symptoms were like a self defense against anxiety. Oh,
(35:58):
I can't work too much if I just become apathetic.
Speaker 5 (36:03):
That was sort of like.
Speaker 4 (36:04):
The idea that I think decission fell into Yeah, it is.
It is really interesting, especially considering like today sort of
the lines between anxiety and depression and the yeah.
Speaker 5 (36:16):
Yeah, I mean there is. There is so much overlap
with anxiety symptoms of anxiety and depression, and a lot
of times depression is a lot harder to treat if
there is an anxiety component versus if there isn't.
Speaker 3 (36:29):
Yeah.
Speaker 5 (36:29):
So that's really interesting, it is.
Speaker 4 (36:30):
It's yeah, the history of anyway we could yeah.
Speaker 5 (36:34):
I know that, like the history of psychiatry. Wo oh,
that's not this episode.
Speaker 3 (36:40):
That not this episode. Yeah.
Speaker 4 (36:42):
And so there was a distinct diagnosis for depression separate
from anxiety, but it was reserved for extreme, like really
severe cases that involved psychosis.
Speaker 5 (36:54):
Okay. Interesting.
Speaker 4 (36:55):
So from the nineteen fifty two DSM describing quote unquote
psychotic depression reaction quote, these patients are severely depressed and
manifest evidence of gross misinterpretation of reality, including at times
delusions and hallucinations end quote. Okay, so it's it's not again,
it's a very narrow definition compared to what we have today, exactly. Yeah,
(37:19):
And things like melancholia or melancholy had also been a
popular diagnosis in the late eighteen hundreds and into the
nineteen hundreds, and it was believed to have a biological
basis until Freud. That biological basis and melancholia in general
kind of fell out of favor as Freudian theory took over,
(37:40):
which held that biology had nothing to do with it.
Speaker 5 (37:42):
Yeah, it was all your mom and stuff.
Speaker 3 (37:44):
It's all your mom.
Speaker 5 (37:45):
Yeah, that's the conclusion of freud the end.
Speaker 4 (37:52):
So all this is to say that in the nineteen
fifties and nineteen sixties, depression was not the widespread, broadly
defined cli entity that we think of today, and so
it really wasn't seen as a major problem warranting extensive
searches for effective treatment or better understanding of its underlying cause. Wow,
(38:13):
the framing of it really prevented interest. I think, yeah,
and like consideration.
Speaker 3 (38:18):
Yeah.
Speaker 4 (38:19):
And some treatments did exist, such as electroconvulsive therapy, which
was used for severely depressed patients with psychosis in the
nineteen forties, and it seemed effective in the short term,
but no one knew why, and it quickly fell out
of favor as long term negative effects emerged, like extreme
memory loss and other things. Amphetamines were prescribed for the
(38:43):
Blues in the nineteen forties and the nineteen fifties.
Speaker 5 (38:46):
Okay.
Speaker 4 (38:47):
And then there were combination amphetamines sedatives to treat anxiety
and the depressive symptoms that came with it.
Speaker 5 (38:55):
Oh gosh, okay, upper runed downer, mix it all up, Okay, great, yep.
Speaker 4 (39:02):
But again none of these drugs were antidepressants. They were
treating what was understood at the time to be a
symptom of anxiety. What turned things around was tuberculosis.
Speaker 5 (39:18):
Stop it, everything is tuberculosis.
Speaker 3 (39:22):
I was just, yeah, I have here.
Speaker 4 (39:23):
John Green was right, everything really is tuberculosis.
Speaker 5 (39:26):
Stop it, yes, tell me more, Okay, okay.
Speaker 4 (39:30):
So, as the nineteen fifties rolled around, the hunt for
an effective tuberculosis treatment had been going on for decades
with how much success. And then a new drug called
iproniazid okay, m hmm came on the scene. And if
you listen to our book club episode on the Black
Angels by Maria Smilios, this is one of the new
anti tuberculosis drugs that the nurses at Seaview Hospital on
(39:52):
Staten Island tested out on their patients.
Speaker 5 (39:55):
Okay.
Speaker 4 (39:56):
And when these patients, when these tuberculosis patients were getting
this drug, their moods improved, their appetite increased. There were
even reports of dancing in the wards. Whoa yep. Initially,
these positive side effects of euphoria, psychostimulation, increased appetite, improved
sleep weren't of much interest to the drug manufacturer, especially
(40:18):
since ipronized It only did so so when it came
to treating tuberculosis, its sister drug, ionized It did much better.
But the pictures of dancing patients that seeview caught the
attention of one psychiatrist, doctor Nathan Klein, who wondered whether
ipronized It held the answer to a question that had
(40:39):
long interested him. If something like schizophrenia was caused by
an excess of psychic energy quote unquote, which is kind
of the idea at the time, could depression be caused
by a lack of it? Could this tuberculosis drug, with
its euphoric effects increase psychic energy. So began a trial
(41:01):
using Iproniazid to treat his patients who had severe depression
at the state hospital where he worked. He detected an
improvement in seventy percent of them, wow, which he reported
in nineteen fifty seven, and so with this, iproniazid came
the became the first of our modern antidepressants on the
market ANDI or a monoamine oxidase inhibitor. Isn't that unbelievable
(41:28):
from tuberculosculosis.
Speaker 5 (41:30):
Wow, Jock Green had it right.
Speaker 3 (41:33):
He had it right.
Speaker 4 (41:34):
I just I love that it was this researcher, the
psychiatrist who saw these pictures and was.
Speaker 5 (41:39):
Like, whoa they seem pressed?
Speaker 1 (41:42):
Ye?
Speaker 3 (41:43):
Can we use this?
Speaker 5 (41:45):
How interesting?
Speaker 3 (41:46):
Yeah, that's it's amazing. Yeah.
Speaker 4 (41:49):
And the popularity of iproniazid and other similar MAOIs that
quickly appeared at following iproniazid in the late nineteen fifties,
it was they were fairly lived as a as a
popular antidepressant because while they did seem to be effective
in treating depression, they came with some pretty nasty side
effects constipation, difficulty urinating, even jaundice. Death could occur if
(42:14):
someone eat cheese or chocolate.
Speaker 5 (42:17):
Yeah, and drug tresines.
Speaker 4 (42:19):
Drug companies withdrew the drug and it would soon be
replaced by another class of drugs, the tricyclic antidepressants or TCAs,
which were approved.
Speaker 3 (42:28):
In nineteen fifty nine.
Speaker 4 (42:30):
And these had first been tested as a possible treatment
for schizophrenia, where they were found to be not effective. No,
but definitely not definitely not Again it was all like depletion,
you know, that great sort of the sea cell of
what do we want the balance? Yeah, exactly, But these
these TCAs did show some positive impact for people with
(42:53):
depressive symptoms. At side effects again left something to be desired, dizziness,
memory impairment, drowsing, et cetera. But I just think it's
amazing that we keep finding antidepressants when we're not looking,
which speaks to this phenomenon that I mentioned at the
very beginning, like sometimes we have these drugs that are
effective for certain conditions we don't know why, right, And
(43:14):
stories like MAOIs and TCAs show us that we don't
necessarily have to know how something works to develop effective treatments.
And even if we think we know, like we thought
we did with SSRIs, because this was like this was
a more targeted drug development, and we're proven wrong about
(43:35):
our initial hypothesis or not totally right, we can still
make a difference.
Speaker 5 (43:40):
Yeah.
Speaker 4 (43:41):
Yeah, Okay, so we're finally at the point in the
story where SSRIs.
Speaker 3 (43:45):
Come onto the scene.
Speaker 4 (43:46):
Okay, it's taken us a little bit to get here,
but I feel like it was important to understand the
big picture, like, oh yeah, it's just fascinating, you know,
from two billion, three billion years ago all the way to.
Speaker 5 (44:00):
Till the day in nineteen sixties.
Speaker 3 (44:02):
Nineteen sixties, there you go.
Speaker 4 (44:05):
And so the advent and effectiveness of MAOIs and TCAs
kind of lent support to the idea that depression and
other mental health disorders are related in some way to serotonin, orpinephrine,
and dopamine. So like there's something to the monoamine hypothesis
of depression, right, And how exactly they were involved was
(44:28):
unclear since they both worked in different ways TCAs and MAOIs, Right,
they both led to kind of the same end result.
Speaker 5 (44:36):
Right, you're increasing the amount of these neurotransmitters.
Speaker 4 (44:39):
Exactly, and how you're doing that, that's not really sure.
And how is it improving your symptoms?
Speaker 5 (44:43):
I would really know. No.
Speaker 4 (44:45):
And so it seemed like antidepressants were on a trajectory
of incremental improvements. But like we talked about, those two
existing classes had some serious drawbacks with their prevalent and
sometimes serious or deadly side effects, which were due in
part to how they weren't super specific. They were kind
(45:05):
of ramping up all of those three dopamine, norpinephrin, serotonin.
It was kind of just like across the board. And so,
you know, some researchers thought, well, what if we could
make these more specific, What if you could target just
one of these neurotransmitters, Maybe that would help with the
side effects, Maybe that would get to the root underlying
(45:26):
cause of these disorders. And so by the late nineteen sixties,
interest had gathered specifically on the role that serotonin might
play in depression. Specifically, again it's depletion, with the logic
following that if you could restore serotonin, you could alleviate depression.
We know that that's.
Speaker 3 (45:47):
Not the case.
Speaker 5 (45:48):
It's not exactly the truth.
Speaker 4 (45:50):
It's not exactly the truth, but it was a it
was a hypothesis. Yeah, it's not Yeah, it's anyway, there's
a lot of us were starting points, the starting point exactly.
Speaker 5 (46:01):
Yeah, And so.
Speaker 4 (46:02):
Pharmaceutical companies set their sites on making a compound that
prevented the reuptake of serotonin at serotonin transporters, specifically, meaning
that it had reduced affinity for Nora Bernephrin. So put
that jargon another way, and you've got a selective serotonin
reuptake inhibitor SSR.
Speaker 5 (46:20):
Yeah.
Speaker 4 (46:22):
Eli Lilly found success in nineteen seventy two with a
compound that they called fluoxetine, and thirteen years later it
became the first SSRI approved by the FDA under the
trade name Prozac. And it is interesting to me that
with Prozac with fluoxetine, we did have this plan, here's
(46:45):
what the drug that we want to make, and here's
what we're going to do, and here's how we think
it works. Right, And it still didn't work out, but
it still had some effect. And it's just different than
like ipronize it, which was like, oh, tuberculosis, right.
Speaker 5 (46:58):
It was much more like intentional.
Speaker 3 (47:01):
It was an intentional design. Okay.
Speaker 4 (47:05):
So in the time between PROZACX development and its approval,
which is, you know, decade and a half, depression had
time long time. Depression had undergone quite a transformation really,
so beginning in the late nineteen sixties, clinicians started to
think of it as separate from anxiety, or that what
(47:28):
had been thought of as anxiety was actually depression. So
the depression was both increasing in its prevalence as well
as broadening in its definition. Okay, So the WHO in
nineteen seventy four declared depression much more widespread than previously thought,
affecting one fifth of the global population.
Speaker 2 (47:50):
Wow.
Speaker 3 (47:51):
Yeah in nineteen seventy four.
Speaker 5 (47:53):
In nineteen seventy four, Wow okay, huh.
Speaker 4 (47:57):
And part of this transformation, and also what made such
estimates possible, was the creation of standardized scales by which
to measure and diagnose depression. These scales allowed researchers to
conduct clinical trials where they could track depression symptoms over
time and with or without treatment, and these trials revealed
(48:19):
that by and large, antidepressants were effective in alleviating symptoms
of depression, with some differences among formulations and of course
among different individuals, and their efficacy held whether someone could
identify specific reasons for their depression, like this thing is
going on in my life or this you know, my
(48:40):
dog died, my car broke down, my house was foreclosed upon,
or if they couldn't right so, in response like to
this sort of depression happens, antidepressants work whether or not
you can define a specific incident. The DSM was like,
we need to make some adjustments, and so the three
(49:00):
published in nineteen eighty removed any questions about life circumstances,
family history, triggers, and so forth, and its description of depression.
Speaker 5 (49:09):
Ooh interesting.
Speaker 4 (49:11):
Yeah, so instead it just provided a checklist of symptoms. Yeah, okay,
so because previously diagnoses depended more on whether you could
pinpoint fact life life situations.
Speaker 5 (49:22):
That's so interesting, especially thinking about now, like when you
have life stressors a lot of times you're less likely
to diagnose depression real till yeah, I mean because a
certain amount of depressive symptoms are to be expected with
significant life events, right, and so then it's like a
grief reaction which you then have to separate out from depression.
So that's interesting. I mean, it can certainly lead to depression,
(49:44):
but it just sort of it complicates a picture more
and it sounds like in the past it was like, no,
you need to have that in order to be depressed.
How interesting.
Speaker 4 (49:52):
The transformation's huge, yeah, huge, huge, And so this shift though,
what it did was it it really increased diagnoses across
the board, because now you don't have to say, oh, well,
I don't think I think you're just I think you're
just a little bored, or I think you're just a
little bumped, you know what I mean, Like, I'm not
(50:13):
saying that's exactly what was said, but I think legitimized
no cases of depression where it was like nonspecific right,
life events, Yeah, right. And so when Prozac hit the
market in January nineteen eighty eight, there were many more
people who sought prescriptions for this new antidepressant than there
had been in past decades. Not necessarily because depression overall
(50:38):
was on the rise, like because which it may may
have been just because of the world or whatever, but
also because our framing and perception of the condition had broadened.
People now had the vocabulary to describe the things that
they felt, and then they were often, though not always,
taken more seriously about the impact of this on their
(51:01):
day to day functioning.
Speaker 5 (51:02):
Right.
Speaker 4 (51:04):
By nineteen ninety, this is just two years. Within two
years of its release in the US, Prozac became the
most widely prescribed drug in North America.
Speaker 5 (51:15):
Wow, and just a.
Speaker 4 (51:17):
Few years later, the second most sold drug in the world.
Speaker 5 (51:21):
Wow W.
Speaker 3 (51:24):
This was unexpected. I don't think it illiglally anticipated.
Speaker 4 (51:28):
This Prozac was not the first antidepressant or even the
first SSRI. There were other previous SSRIs but they were
never approved for the US market, and they seemed to
have more side effects, but prozac had fewer side effects,
and so it was considered a safer drug compared to
like TCAs, which meant that physicians were more likely or
(51:50):
felt better about prescribing it not only to their patients
who had like severe depression, but also those with milder symptoms.
The continued pop popularity of prozac and later SSRIs showed
that clearly these medications were working, but how were they working?
Even before their release, researchers knew that these SSRIs were
(52:14):
not acting under the hypothesis of low or imbalanced serotonin
equals depression. That idea had been rejected decades before.
Speaker 5 (52:26):
It's just so fascinating that that doesn't like that is
so often left out of the story.
Speaker 4 (52:30):
It doesn't get translated. It's like, yeah, people are like, oh,
serotonin is not the only thing related to depression, you know,
scream the headlines and it's yeah. All the researchers are like,
what year.
Speaker 3 (52:41):
Is this right? We've known this, I was taught this.
Speaker 5 (52:44):
Said that, who said that it was sorry said that.
Speaker 3 (52:46):
It was Yeah.
Speaker 4 (52:47):
It's a straw man argument, because if that was the hypothesis,
then they would have expected to see You would expect
to see improvement in symptoms in someone very soon after
someone starts taking SSRIs, not after weeks, which is the
timeline that we usually see. But given that these drugs
are effective, serotonin likely plays some role in depression and
(53:09):
other mental health disorders, maybe in like a regulatory capacity.
But even though researchers had long acknowledged that the biological
underpinnings of depression are more complicated than just serotonin.
Speaker 5 (53:21):
Add serotonin, yeh, sprinkle some serotonin.
Speaker 4 (53:25):
Well, serotonin on top, this message didn't reach the general
public until I feel like, relatively recently, you've got again,
like popular media articles or TikTok saying things like you've
been lied to. Antidepressants don't do what we think, and
it's like yeah, or the final nail in the depression
(53:45):
serotonin coffin?
Speaker 5 (53:48):
Is that a real headline?
Speaker 4 (53:49):
Narin, I don't remember it, Okay, I think it actually,
I think it was because researchers again were like, final nail.
That thing's been dead for decades, it's been buried. What
are you talking about? But a few promoted or even
we're behind this misrepresentation of the science of SSRIs. You know,
(54:12):
this is where like this again the serotonin hypothesis as
the straw man argument against these medications, right, and this
I mean to go, I don't want to go too
much into like the motivations or the reasons for this misrepresentation,
because I do think that there is like an anti
psychiatry movement that you don't need drugs, You just need
(54:33):
to pull yourself up by the bootstraps, bootstraps and work hard.
Just get out of bed, clean your house, just do it,
just push.
Speaker 5 (54:39):
Do it, just do it, right. I mean, that's the
same thing as before anyone recognized that depression was a thing, Right,
It's the same, that's the same end result.
Speaker 3 (54:48):
It's the same end result.
Speaker 4 (54:49):
The thing is this, this misrepresentation saying that scientists think
that SSRIs work on depression in this way and they're wrong.
That has the capacity to do real damage.
Speaker 5 (55:04):
Especially to people who are on SSRIs, who have benefited
from SSRIs, who are now in charge of regulating our SSRIs.
Speaker 4 (55:12):
It has or could encourage people to stop treatment under
these false pretenses. And it also just overall deepens mistrust
in science and medicine. The truth is that the general
public has been lied to, or at least not been
told the whole truth about our understanding of SSRIs and depression. Ads,
(55:34):
like pharmaceutical ads, which should be outlawed in my opinion,
for antidepressants, have long claimed that the drugs work by
correcting a chemical imbalance, and these ads reduce these complicated
disorders to a simple issue of brain chemistry. It's a
catchy thing. You got, you know, thirty seconds for an ad.
(55:56):
Of course you're going to say the simplest thing possible.
And what company wants to be like, we don't know.
Speaker 3 (56:01):
How this works.
Speaker 4 (56:03):
Of course they're going to say something like it's a
chemical imbalance. But I think that that under represents or
falsely represents the complexity of the issue and how much
we know or don't know about this. And I think
this trickles down into physicians who will use the same
language when explaining the medications to their patients. Again, not
(56:24):
wanting to sit there in an office, you have five
minutes to talk to your patient, and you don't want
to say we don't know how this works.
Speaker 3 (56:30):
Number one.
Speaker 4 (56:31):
Number two, let me tell you about how serotonin receptors
work in your brain.
Speaker 3 (56:37):
And your gut. Right, I know. So it's laughing chemistry.
It's an imbalance.
Speaker 5 (56:41):
I'm laughing so much erin because I it's my favorite
thing when I get to explain mechanisms to my patients.
So you're in the office or you get to be like, Okay,
this is too detailed, but just give me one and
then and then at the end be like, yes, so
we don't know how it works, but.
Speaker 3 (56:55):
Right, but it's yeah, but no, but most people.
Speaker 5 (56:58):
Don't do that. Yeah, yeah, most people. We also don't
do that, and like, yeah, okay, we learned the mechanism
in med school and then you obviously forget it because
there is way too much to know. And what you
really need to know is do I have something that
can help my patient or not? Right exactly so.
Speaker 3 (57:17):
And I think that, like you know, I was thinking.
Speaker 4 (57:19):
I just I've spent so much time thinking about SSRIs,
like in a very focused, directed way where I'm like, okay,
this these ads for example, or this message I'll say,
whether it's in an ad or in your doctor's office
or wherever, about depression and other mental health disorders being
a result of an imbalance in your brain chemistry. That
(57:40):
message has been really important for reducing stigma and for
underscoring the idea that these disorders are real and that
they can be treated with medical solutions. But by framing
it in this unnuanced way, by not acknowledging that there
are still unknowns, it ignores the need for more research
(58:02):
both on SSRIs as well as depression and other mental
health disorders. It disregards the experiences of many people for
whom these medications don't work, and it minimizes the importance
of non pharmaceutical interventions such as therapy. And it does
a disservice to everyone who uses, prescribes, or researches these
(58:23):
medications or alternative treatments for depression and other mental health disorders.
There is no question that in the decades since Prozac's release,
SSRIs have completely changed the landscape of depression. They have
provided relief to so many people. They've been a life
saving to so many people. They have helped to reduce
(58:43):
stigma surrounding depression and other mental health disorders. They have
forced us to reconsider how we think of mental illness.
They are not perfect, but I don't know anyone who
claims they are, besides maybe the pharmaceutical companies.
Speaker 5 (58:59):
Don't know any neat drug that is perfect.
Speaker 3 (59:02):
No drug, you're perfect.
Speaker 4 (59:04):
Yeah, But I'm I'm excited though for next week, Arin,
when you get to tell me about more about how
much we don't know and how much we do know
about these medications and how we can make them maybe
not perfect but better.
Speaker 5 (59:22):
Hmmm, that's a good one. I probably won't answer that question,
but I will provide quite a lot of data to
support what we do and don't know. And then a
little bit in my opinions about how we talk about
all of this too.
Speaker 3 (59:34):
Oh love it?
Speaker 5 (59:35):
Okay, next week more next subscribe so that you don't
miss an.
Speaker 4 (59:40):
Episode, never miss an EPP. And in the meantime, how
about some reading?
Speaker 5 (59:46):
How about some reading? I'd love to do more reading, Aaron.
Speaker 4 (59:51):
I have a bunch of sources, but I'm going to
shout out three in particular. There's by Whittaker as Media
in nineteen ninety nine, The Discovery of serotonin and its
role in neuroscience from Hillhouse and Porter twenty fifteen, A
brief history of the development of interdepressant drugs from Monoa
means to glutamate, and then kind of just the broad scope,
(01:00:12):
big picture of depression and the advent of SSRIs and
how that changed the landscape. There was a couple great
chapters in a book called Mind Fixers Psychiatry's Troubled Search
for the Biology of Mental Illness by Anne Harrington, and
I've got more I'll post.
Speaker 3 (01:00:31):
Them on our website.
Speaker 4 (01:00:32):
This podcast will kill you dot Com.
Speaker 5 (01:00:35):
Thank you again so much to the providers of our
first hand account. We appreciate you so so so much.
And thank you to everybody who wrote in to share
your story about SSRIs. We really appreciate it.
Speaker 3 (01:00:47):
Yeah, thank you, Thank you.
Speaker 4 (01:00:48):
Thank you also to Bloodmobile now on Instagram for the
music that you provide for this episode in all of
our episodes.
Speaker 5 (01:00:57):
Thank you to Leanna and Tom and Brent and Pete
and Mike and Jess and everybody exactly right for all
your help making these episodes happen.
Speaker 4 (01:01:09):
Yes, thank you, and thank you to you listeners and
watchers and anyone who partakes in the podcast in some way.
Speaker 3 (01:01:16):
We really appreciate it that we do. Thank you. Thank you.
Speaker 5 (01:01:20):
Thank you as always to to our patrons for your
support over on Patreon. We really really appreciate it. It means
a lot.
Speaker 3 (01:01:26):
We do well.
Speaker 5 (01:01:28):
Until next time, wash your hands, you filthy animals,