0:00

From the greenhouse, where it's currently raining and it's

0:02

gonna be loud, sorry. It's the Adam Ragusea podcast,

0:04

episode 84, and let me tell you something.

0:07

I, a couple of months ago, started

0:09

taking an antidepressant called

0:11

Sertraline, which you probably know

0:13

from the brand name Zoloft,

0:16

and it has been dismaying,

0:20

but more than that, fascinating, the

0:23

extent to which this medication has affected

0:25

my digestive system and my appetite. Like,

0:27

profound stuff. And I've looked it up,

0:30

I've done the Googles, and I have

0:32

seen that this is, in fact, incredibly

0:34

common, that all kinds of antidepressants have

0:36

a profound effect on appetite, and on

0:38

the gut in particular. I want

0:42

to know why, so I invited my

0:44

brother on the show. Hey, it's Dr.

0:46

Tony Ragusea, who is not just my

0:48

brother, but he's also a board

0:50

certified clinical psychologist at

0:53

Evangelical Community Hospital in

0:56

Lewisburg, Pennsylvania. You got that right. That's where I'm at.

0:58

All right, all right. I'm gonna keep going, I'm gonna

1:01

keep going. And in addition to

1:03

his doctorate, he also has a, what

1:05

is it, a postdoc or a second

1:07

master's in psychopharmacology? I have a postdoctoral

1:09

master's, so it's a master's degree intended

1:11

for people who already have their doctorate,

1:13

and just, you know, like, you know, just like can't get enough.

1:17

Right, okay. It's basically a postdoc. Okay.

1:19

So like, this is what you do, okay? So maybe

1:24

a good place to start would be,

1:26

basically, how do we think that these

1:29

particular kinds of antidepressants, SSRIs, basically, how

1:31

do we think those work? Okay,

1:35

so the SSRIs. Okay,

1:37

so let's define some terms here.

1:39

So SSRI is an abbreviation that

1:42

stands for Selective Serotonin Reuptake Inhibitor.

1:44

And you were so good, you

1:46

said abbreviation instead of acronym, because

1:48

it would only be an acronym if you pronounce

1:51

it SSRI. Fine.

1:56

Anyway, continue. Have it your way. So

2:01

an SSRI, take

2:04

your pick, abbreviation acronym, it

2:07

means selective serotonin reuptake inhibitor.

2:10

And what they

2:12

do is they block the reuptake

2:14

of serotonin in

2:18

the brain, it's blocked going

2:21

back up into the neuron. So

2:23

what happens is that serotonin gets

2:25

released from certain neurons

2:27

in the brain. And the drug

2:30

winds up blocking the transporter

2:33

which carries the serotonin

2:36

back up into the neuron. So

2:39

the effect is actually on a

2:41

transporter molecule. And

2:43

by blocking the transporter

2:45

molecule, it prevents serotonin from

2:47

being brought back into

2:49

the neuron where it would normally

2:52

get recycled and reused. But by

2:54

being left out in the synaptic

2:56

cleft, which is the gap, this

2:59

tiny, tiny, tiny, tiny, tiny,

3:01

tiny little gap that exists

3:03

between two neurons, by

3:05

sitting out in the gap longer, the

3:09

receptors on the postsynaptic

3:11

neuron have a

3:13

longer amount of time to

3:15

attach to serotonin molecules. And

3:17

so the end effect is

3:19

that you have more stimulation

3:22

of the postsynaptic neuron than

3:24

you would have had otherwise.

3:26

However, if you'll bear with

3:28

me for another second here.

3:31

I'm there, I'm so there. Okay, all right. That

3:34

is- I love having my postsynaptic thing stimulated, whatever.

3:36

Not a lot of people I've met can do

3:39

it, but you know. Yes, that's

3:41

right. So

3:43

there's more activity in the postsynaptic

3:46

neuron. And

3:48

what ends up happening is that, so

3:50

you might think that that's the therapeutic

3:52

effect right there, but that's probably not

3:55

the therapeutic effect. Okay, that's not where

3:57

it comes from. What

4:00

probably happens is that by

4:03

overstimulating the postsynaptic neuron, like

4:06

boosting the stimulation, what winds

4:08

up happening is that the

4:11

receptors on the postsynaptic neuron

4:13

winds up closing off. The

4:16

specific term for that is downregulating.

4:20

So the number of receptors on

4:22

the other side decreases. And

4:25

when they decrease, that results in

4:27

an overall

4:29

less responsive postsynaptic

4:32

neuron. So it's

4:34

sort of like the postsynaptic neuron is saying, okay,

4:36

enough already. I've got the stimulation. This is too

4:38

much. This is more than we usually do. I'm

4:41

going to slow things down here. And

4:44

you might say that... That sounds like classic desensitization. Yeah,

4:46

that's right. You're kind of... Yeah, that's right.

4:48

Exactly. You're sort of

4:50

desensitizing the postsynaptic neuron. So you might say

4:53

then, well, okay, well, is that the therapeutic effect? And

4:55

the answer, of course, is that no. The

4:58

way I explain it is

5:02

that that is what we can see

5:04

in this process is like imagine

5:07

like a giant machine, okay? That is

5:09

your brain. And it has like billions

5:11

of gears in it. And

5:13

you're staring down at this machine with billions

5:15

of gears in it. And

5:18

someone says to you, yeah, we don't know how

5:20

exactly how this machine works. But

5:23

something's broken. It's not working. But

5:26

it's been like thousands of years since anyone's had to do any

5:28

repairs on it and no one knows how to fix it again.

5:30

So can you like try your best to fix it? And

5:34

you're looking at this giant box of gears thinking, well, how

5:36

do I fix this? And you've got a rock in your

5:38

hand. And you say, okay,

5:40

well, that gear right there looks a little wonky

5:42

to me. Like a little vibrating a little bit.

5:45

If I hit that gear with the rock, then

5:48

it might go back into place and work better. So

5:51

you drop the rock into the machine

5:54

and it hits that gear and thumps it a

5:56

little bit. But it doesn't

5:58

stop there, okay? up

6:00

falling into the box of gears

6:02

and winds up having less

6:06

predictable downstream effects. So

6:10

what we think is that the

6:13

downstream effect of down regulating

6:15

the postsynaptic receptors ultimately

6:17

goes down to the genetic level

6:20

and alters the way how genes

6:23

express themselves. And

6:25

then that change works its way back

6:27

up to the cellular level in some

6:29

way that we do not understand. Wow.

6:34

Yeah. Well,

6:36

it's great that we're all on them. Yeah,

6:39

exactly. Well, let

6:42

me – so I want to go ahead

6:44

and specify – you can say whatever you

6:46

want and you've certainly earned the opinion, but

6:48

given that it's my show, I feel like

6:50

I should also say that I

6:53

want you, dear listener, to seek treatment in

6:55

whatever way makes sense to you and whatever

6:58

you feel you need, I want you to go

7:00

to someone and try it, someone

7:03

reputable. So

7:06

any bad things that I

7:08

might say now about my

7:10

experience with antidepressants is entirely

7:12

personal and we all have to

7:14

make our own cost benefit analysis and I'm not trying

7:16

to scare you away or anything, right?

7:18

Yes, correct. Okay.

7:21

Do you – you have privately

7:23

shared with me like a top-line opinion

7:25

on the value of SSRIs. Do

7:29

you feel comfortable saying that in public right now? Yeah.

7:35

So, okay, let me answer that question this

7:38

way. So I think

7:41

that the public perception of

7:44

SSRIs, which are – and that's

7:46

only one type of antidepressant, right? There are

7:48

several updates. There are several other, right? That's

7:50

right. They are the

7:53

most commonly prescribed antidepressants currently, but there

7:55

are many others and

7:57

they all work slightly differently.

8:01

And I think the public

8:03

perception about antidepressants, just in general,

8:05

because I don't think the public

8:07

really understands the difference between them

8:09

all. But I think the public

8:11

perception is that antidepressants are helpful

8:14

medications that work really well at

8:16

fixing depression and maybe even anxiety.

8:20

The reality is that

8:22

antidepressants are pretty mediocre

8:26

psychotropic drugs as

8:28

a class. They

8:32

are more helpful in certain types of people,

8:35

in certain situations. So

8:37

what I say here needs to be taken with

8:40

a grain of salt here, your results

8:42

may vary. And I can't

8:44

predict what any one person's response will

8:46

be to these medications. But

8:50

in general, SSRIs and other antidepressants

8:52

tend to work better on people

8:55

with more severe types of depression

8:58

and on people with more chronic

9:00

types of depression that

9:04

seem less likely to be related to

9:06

a specific stressor in

9:09

a person's life. So

9:13

if it seems like the person is upset, and

9:16

very, very upset by something that's happened, let's

9:18

say it's the death of a loved one,

9:20

okay? That kind

9:23

of a situation is one that

9:25

probably isn't going to get much

9:27

benefit from antidepressants. But

9:29

someone like me who basically won the lottery in

9:32

life and yet I'm going completely insane. Maybe

9:35

it's just something that's wrong with my brain,

9:37

right? Possibly, although there's really no evidence if

9:39

there's anything wrong with your brain. Let's be

9:41

also clear about that. There's really

9:43

no evidence that people who benefit

9:46

from antidepressants have, well, okay,

9:48

I'm gonna qualify that. Okay,

9:51

there is some evidence that people

9:53

who are depressed, okay, clinically depressed,

9:55

not just unhappy, not

9:57

just sad, not just a little bummed

9:59

out. not having a bad week,

10:01

okay, these are clinically depressed people

10:03

who have clinically

10:05

significant impairing symptoms and have

10:08

had them for a sustained

10:10

period of time. Those

10:13

folks, their brains do

10:15

work differently in MRI

10:17

studies, functional MRI studies.

10:20

What you can see is that

10:22

that certain parts of the brain

10:24

are smaller, so

10:27

there's evidence that the brain is under

10:29

stress and it's resulting in

10:31

a shrinkage of overall volume of certain

10:33

parts of the brain. That's what we

10:35

believe is going on there. That tracks,

10:37

let me tell you. But whether that's

10:39

a symptom of depression or a cause

10:41

of depression

10:46

is unclear, okay, so it may be

10:48

that it's just the stress of being

10:50

that depressed that results in the brain

10:52

changes. We haven't necessarily,

10:55

we haven't identified a vulnerability

10:57

in certain people's brains that

10:59

would explain why air-depressed and

11:01

other people aren't, okay. There's no known

11:04

simple genetic vulnerability or structural

11:06

difference that would explain it.

11:10

But the big picture thing that I feel I want to

11:12

make sure that we communicate at this juncture

11:14

before we move on to talking about the effect

11:16

of such antidepressants on our digestion and our appetite

11:18

is that you don't have to take Dr. Ragusea's

11:20

word for it, you don't have to take Mr.

11:22

Ragusea's word for it, which you really shouldn't take

11:24

at all. Just go

11:26

on the Google and look for recent literature

11:28

reviews on SSRI efficacy or something like that,

11:31

and they'll all tell you the same basic

11:33

thing, which is that the observable clinical effect

11:35

of these drugs is pretty modest in most

11:37

people. That's right. And therefore must be weighed

11:40

against the side effects, which for me

11:42

have been considerable. Which we'll get to

11:44

in a second. And so the

11:48

effect size, the statistical effect size

11:50

in antidepressants as a whole is

11:52

about 0.3, which

11:56

is a relatively... A relatively...

11:58

What? Which is relatively... small.

12:00

Did you just say that? Yes, I

12:02

did just say that. So

12:05

what that means is, so think

12:07

of a fact-side... Is

12:09

that a controversial scientific evaluation on your part

12:12

or as well? No, I mean... No,

12:15

there's going to be some variability depending

12:17

on the study that you look at

12:19

and of course the population that is

12:21

studied. Okay, so you may get different

12:23

variability. This is kind of an overall

12:25

meta generalization. And

12:30

for those of you who didn't

12:32

take statistics in college, an effect

12:34

size, the physical effect size is

12:36

a number between zero and one usually. It

12:39

could be

12:41

negative as well as positive. So

12:43

it would be negative zero point

12:45

something. But it's between zero and

12:47

one. And it's

12:50

an estimate of how

12:53

much better the drug is beyond

12:55

what you would get from the

12:58

placebo effect below. Okay,

13:01

so antidepressants have a

13:03

fairly substantial placebo effect.

13:05

As do most

13:08

psychotropic medications

13:10

used to treat mental illness. They all

13:12

have a pretty sizable placebo effect. What

13:15

I'm saying is that the

13:18

benefit, if you nullify that

13:20

placebo effect, antidepressants have

13:23

a relatively small effect beyond

13:25

that. So they're not

13:27

really adding much more beyond a placebo. And

13:31

most people, again there are exceptions. And

13:34

indeed in most people, from what I've read, the most

13:36

common side effect, at least when you first start these

13:39

drugs, and these are drugs you have to like take

13:42

for many weeks to let them build

13:44

up in your system before you start

13:46

to see clinical benefits. And that's probably

13:48

why they take several weeks, by the

13:50

way. That's the amount of time it

13:52

takes for that epigenetic response to take

13:54

place. Oh, for that gene

13:56

expression to actually happen. That's right. its

14:00

way back up to the surface where it

14:02

results in cellular changes, right? So

14:05

that process takes several weeks. Okay.

14:07

But it is very common in the

14:10

initial, especially in the initial phases when

14:12

you first get on for people to

14:14

have upset stomach and diarrhea with SSRIs.

14:19

Yes, my life force has been leaving my

14:21

body at an unprecedented rate. If

14:23

you can hear the sound of the rain outside the

14:25

greenhouse, that's basically been my life. Um,

14:29

so do we have, what would you

14:31

think based upon the science that you have looked at,

14:33

what is your best guess as to why these drugs

14:35

cause upset stomach and diarrhea? So

14:39

the reason for those particular

14:41

side effects probably

14:43

has to do with the

14:46

reality that most of

14:48

the serotonin receptors in

14:51

your body in cells are not

14:53

located in your brain, but are located

14:56

in the rest of your body, particularly

14:58

the gut. Yeah.

15:02

What the hell is their serotonin doing in

15:04

my gut? What is its job there? Produced

15:06

there? Lots of, lots of,

15:08

lots of hormones and all kinds of crap gets

15:10

made by cells in the, in the gut and

15:12

gut lining, right? Uh-huh. That's right. Yeah, sure. It

15:14

gets, it does get made there, um, uh,

15:19

in, in some cells and then there are other

15:21

places where it has effects or it does get

15:23

made. So for example, uh, platelets. Uh,

15:26

platelets rely on, uh,

15:28

on serotonin to have

15:30

their clotting effect. Okay. Um,

15:34

and, but platelets don't produce,

15:36

uh, serotonin, uh, but

15:38

they do uptake it. They

15:41

do, they do receive it. And so when

15:43

you use an SSRI and it messes with

15:45

the transporter that connects the

15:47

serotonin to the platelet, it,

15:49

it's, it reduces the clotting effect

15:52

and that results in a, um, a

15:55

slight but notable increase

15:57

in risk of GI bleeding.

16:00

particularly for people who are at risk for that.

16:03

People who are taking NSAIDs or elderly

16:05

people. But

16:07

in the cases of gut serotonin, it's basically, do

16:09

we have, is

16:12

the drug having the same effect that it has

16:15

on the brain, it's doing the same thing to

16:17

the gut, it's preventing the reuptake of serotonin in

16:19

the gut and that's interfering with normal gut processes

16:21

in some way and causing inflammation? That's

16:25

my understanding. Understand that I am

16:27

not a gastroenterologist or other specialist

16:30

in the gut. That's

16:32

okay. I've done my research and

16:34

what you just said is basically what they

16:36

say. Yes, yes. Yeah,

16:40

so my specialty of the brain, trust me,

16:42

that's enough. Yeah,

16:47

but all this talk about how

16:49

the gut is the second brain

16:51

is not just fodder for cheap

16:53

supermarket magazines, right? That's kinda, seems to be

16:55

kinda real in a way. The

16:58

side effects you mean? No, that

17:00

the gut is the second brain. Oh, the gut is the second

17:02

brain, right, yes. Profound

17:04

interaction between gut and brain.

17:06

Yeah, yeah, particularly the gut

17:08

microbiome, right? Which is its own

17:10

kinda thing. Yeah,

17:12

I mean the gut microbiome

17:14

and there's all kinds of things

17:16

going on with the gut. It's a really

17:19

complicated system and we're

17:21

just beginning to understand its

17:23

connection to your mood

17:26

and mental health, but

17:29

it's clear that it does have one. But

17:32

it's gonna take us many years to tease all that

17:34

apart. No

17:36

doubt. The search goes on.

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You need Indeed. And we

19:09

need my brother, Dr. Tony

19:11

Ragusea, to talk about why

19:15

these medicines seem to impact appetite.

19:19

I will put my cards on the table

19:22

and say that long,

19:26

well, as you,

19:28

my brother, who has known me for 41

19:30

years, as you know, and

19:33

as the viewers who have known me for about

19:35

five years, they know that my body composition tends

19:38

to kind of like go back and forth a

19:40

lot. That whatever is going

19:42

on in my life and my brain tends to manifest

19:44

in my body in really obvious ways. And

19:47

so where was I? I, you

19:49

know, sort of toward the end

19:51

of summer, early fall, I kind of like

19:53

rocketed from like 190 to 210. And

19:58

then around there is where I had my. does

22:00

it. And

22:02

so yeah, this morning I was down

22:04

to like 193. And

22:07

this is complicated for me, because

22:09

I know that a lot of

22:11

my psychological problems are

22:13

deeply intertwined with very

22:16

old body image issues that I have. And so

22:18

it's to me kind of this, you know, there

22:20

be dragons, this is hazardous. Because

22:23

I don't really trust

22:25

myself to make smart

22:27

decisions regarding the cost

22:30

benefit analysis of this medication. I

22:32

also want to go ahead and make sure that

22:34

the listeners understand that lest you are thinking that

22:37

you should, if you want to

22:39

lose some weight, just go hop on some, go

22:41

tell a sob story to your physician and hop

22:43

on some Zoloft. Be aware that like lots of

22:46

people have the exact opposite side effect. They tend

22:48

to gain a lot of weight, eat

22:50

a lot more, get a lot hungrier. So please don't

22:53

be doing that. The question

22:55

is, why do these drugs affect our appetite?

22:58

So profoundly. Well,

23:00

okay, hold on now. In

23:03

me. Yeah, in you. That's right. One out of one

23:05

Adams. Yeah. That's

23:08

100%. All right. That's a hell of a

23:10

finding. It is. One. But

23:13

you know, the joke I

23:18

just told Lauren, I said, something happens once. It's a

23:20

funny story. You tell it a party. If it happens

23:22

three times, it's journalism. If it happens a thousand times,

23:25

it's science. So

23:30

the overall data, it doesn't

23:33

suggest that antidepressants generally

23:36

have a major effect on

23:38

people's appetite and weight changes.

23:40

Okay. We have psychotropic that

23:42

have much bigger effects

23:44

on people's appetite than the

23:47

typical SSRIs. Okay.

23:50

Such as the

23:53

antipsychotics, the

23:59

tricyclic, like antidepressants may have

24:01

a greater effect because

24:04

of their histamine effects. And that's largely

24:06

the culprit in psychotropics that cause a

24:08

lot of weight gain is

24:11

its effects on histamine. When

24:14

you block histamine, then

24:17

that increases appetite leads to weight gain.

24:21

But the SSRIs don't have a histamine

24:23

effect. And while,

24:26

yes, I think that the

24:29

overall, I think, belief

24:31

is that the antidepressants can't, the

24:34

SSRIs can still cause weight gain

24:36

or weight loss, more

24:38

likely weight gain. It's

24:41

usually modest. And it's

24:43

usually in people who have

24:45

had it, they've been taking these medications

24:47

for a long time, maybe

24:50

over a year. But

24:53

there are definitely, I think, cases

24:55

of people that gain, maybe, they

24:58

may gain 10 pounds over

25:01

several weeks, maybe a couple of months

25:03

of taking an SSRI. I'm

25:06

not saying that that doesn't happen or can't

25:08

happen. But the other thing that is unclear

25:12

is whether it's actually the SSRI that causes

25:14

that weight gain or weight loss, or

25:17

if it's another factor. And maybe only

25:19

indirectly the SSRI. So what I mean

25:21

is that, understand

25:25

that people who are really depressed tend

25:27

to have appetite disturbance as a symptom

25:29

of their depression. And

25:31

depression itself, the distress

25:34

of depression can

25:36

lead people to eat more as

25:38

a way of comforting themselves, or

25:41

it may cause people to eat less. Because

25:44

some people who are under stress

25:46

just tend to eat less. Like I'm one

25:48

of those, why I eat less under stress.

25:50

Nuclear appetite, yeah. Yeah. So

25:54

that may be the cause of the

25:56

weight change right there. It's just how

25:59

people feel. But

26:03

we don't actually know if

26:07

the SSRI in any one person

26:09

is causing their change in weight.

26:11

It could be their mood. It

26:14

could be that the SSRI is

26:16

having an effect on the person's mood that

26:19

in turn affects their eating habit. So for

26:21

example, one of the most common ways that

26:24

the SSRI make people feel is they

26:26

make people feel less. Yeah,

26:29

exactly. What I

26:31

mean by that is that

26:33

people on SSRIs will often

26:35

say things like, I feel

26:38

numb or apathetic or

26:42

more indifferent

26:45

to whatever stress is going on in their life. And

26:49

so because they feel less

26:51

of things, that may cause

26:53

them to eat less if

26:57

they were already overeating. But

27:01

it also might lead them to eat more

27:03

if they're not paying as close attention to

27:05

what they're eating. So

27:08

there are ways in which the effects of

27:10

SSRIs on people could affect their eating habits.

27:14

And then it's also possible that

27:16

the SSRI itself could have some

27:18

effect on changing appetite directly because

27:21

there are several

27:23

serotonin receptor subtypes. And

27:26

we know that at least some

27:28

of them have a direct impact

27:30

on modulating your

27:32

appetite. That

27:35

said, again, it's unclear that the

27:37

SSRIs are always to blame for

27:39

changing appetite. Sure. No doubt. I

27:42

think people get that asterisk. Okay, okay. But here

27:44

– let me tell you something. Okay. Eyewitness

27:48

testimony should be

27:50

nearly worthless in court or in science,

27:53

but here it is. So I

27:56

do think that I am a particularly self-aware

27:58

person, and I am a self-aware person. particularly

28:00

good at articulating

28:03

my feelings. And

28:06

with that background, like I, in as much as

28:08

a person can be sure about such a thing,

28:10

I feel pretty sure that

28:12

this pill is having a direct

28:14

impact on my appetite. It really

28:16

feels like that. It

28:19

does not feel like anything having to do

28:21

with my mood. I feel I have felt

28:23

my mood stabilize. I've gotten that kind of

28:25

weird, numb kind of

28:27

robot thing where things that should

28:30

feel really good don't feel as good as they should, but

28:32

the flip side is also true and that's great. But

28:37

anyways, it just feels

28:40

really physical. And my

28:43

little hypothesis that I went looking for

28:45

some science to back to, because I

28:47

did what the internet is for,

28:49

which is to confirm what you want to believe.

28:52

So I went looking for other people to

28:54

confirm my preconceived notion about what's wrong with

28:56

me. And I found like very little, you

28:58

know, science one way or another, because it

29:01

feels like it could be a gut thing. You

29:03

know, we know from other research, the

29:06

extent to which gut

29:09

dynamics and gut microbiome in

29:11

particular affect appetite. And

29:13

we have these mouse studies where they'll just transplant

29:16

poop from one mouse's gut to

29:18

another mouse and that mouse will

29:20

end up developing the body composition

29:22

of the first mouse. Right. And

29:26

so it seems to me that a very

29:28

likely thing that could be going on here

29:30

is that either by directly

29:32

affecting my guts or

29:35

by just agitating my gut such that I'm shitting

29:37

out my life force and therefore depleting

29:40

my gut microbiome, something

29:42

that was causing some bug that was

29:44

in there that was dominant previously and

29:46

causing a biological chain of events that

29:48

resulted in me being hungry, especially

29:51

at night. Right. That bug,

29:53

I think that I think I flushed

29:56

out that bug. That's my

29:58

best guess. That's what it feels like. It

30:00

feels profound and physical. It doesn't feel like

30:02

it's happening in my brain. Yeah,

30:05

well, and so I can't rule that out and

30:07

yeah. No, no, no, no, I can't.

30:09

And like no one, I just went like looking for

30:12

life studies along these lines. There's like, I mean, people

30:14

are thinking about this, you know, indirectly and approximately in

30:16

all kinds of ways. But like, yeah, this is not

30:18

a thing that anyone, I'm not, no one can confirm

30:20

or deny what I just said. But

30:22

you, as a scientist, I'm asking if you're honest impression.

30:25

Yes, I think that's

30:27

definitely possible. Definitely,

30:29

I think it does occur in people that

30:32

they have a particularly strong reaction to these

30:35

kinds of effects of SSRIs. And

30:38

I can't, you can never predict who will and who

30:40

won't. That's the other thing. You never know who's going

30:42

to have what kind of reaction. Indeed.

30:44

Yeah. But further, and why I

30:47

feel this experience has been interesting for me and

30:49

why I kind of wanted to get on the

30:51

internet and talk about it. Well, there's two reasons.

30:53

One, I can't talk about anything on

30:55

the show other than what I'm actually thinking about

30:57

this week. So, you know,

30:59

that's just why what it is. It's not necessarily that I want

31:01

to be talking about this publicly. It's just that I can't talk

31:03

about anything else right now. So

31:06

here there's that. The

31:08

other thing is that,

31:10

you know, every

31:12

time I've had an experience where

31:15

a medicine or a recreational drug

31:17

or a sickness or something, you

31:21

know, provoked like a very strong swing and appetite

31:23

in me. I have been reminded of the extent to

31:25

which I suspect

31:28

much of the variation in body composition that

31:30

we see across the human race is the

31:32

result of factors that are beyond our control.

31:35

You know, like smug son of a

31:37

bitch over there who's super skinny may think it's because

31:39

he has better self control and really it's just that

31:41

he has less ghrelin or whatever. I

31:45

mean, no doubt those

31:47

higher functions are also relevant to these

31:49

discussions. Of course they are. But I

31:51

just feel it seems obvious that the

31:53

lower functions are also highly relevant and

31:57

we should be that should

31:59

maybe. let us let ourselves

32:01

off the hook a little bit sometimes and

32:04

probably more importantly, let other people off the hook

32:06

sometimes, I think? Yeah,

32:09

well I think- But you're a judgy son of

32:11

a bitch, so whatever. Oh man. You skinny bitch,

32:13

go ahead and talk. Oh man, it

32:16

all comes out, all the resentment. Well so,

32:19

well no, no, no, no, so here's, okay, I mean you wanna

32:21

talk about it, let's talk about it. So here's the thing, no,

32:24

no, no, I mean I guess I, because you,

32:26

you know, look, brothers torture each other

32:28

and I have, you know, long

32:30

since forgiven you in my own mind for

32:32

any torturing that you did of me, right?

32:35

Okay, that's just how it

32:37

is, okay? But

32:39

you did torture me about my weight a lot when I

32:41

was a kid. I did, yeah. But the

32:43

record's so good. And I always, indeed, exactly,

32:45

and I always took it as you, I

32:49

just took it at face value, right? You

32:53

know, skinny guy feels superior to fat guy,

32:55

so, you know, but honestly,

32:57

you know, what I would like to ask

33:00

you about is, I

33:02

mean, in retrospect, you were,

33:05

you were just a, you were a small kid

33:07

growing up. You were a slight kid and you

33:10

got pushed around a bit. And

33:12

was this you

33:14

dealing with that feeling

33:18

or deflecting that feeling onto me

33:20

in some way? Um,

33:23

first of all, I don't

33:25

know that I remember a

33:30

long time ago, but

33:33

my inclination, my hunch, is

33:37

to say that, um, no, I

33:47

don't think it had much to do

33:49

with deflection. And I honestly, I honestly

33:51

didn't see, like,

33:54

your difference in sizes between you and me

33:56

is like a better

33:58

than, less than kind of dynamic. It

34:02

was just a lever that you could pull to torture me.

34:04

Yes, that's really what I think it was more about. Whatever

34:07

it was, it was also a subway. I'm

34:16

not using this as a

34:18

full excuse here. It was a somewhat different

34:20

time where our... Oh,

34:23

it was radically different. No, no, no.

34:25

It was radically different. It

34:27

was the kinds of things that our

34:29

parents did vis-a-vis this issue with me.

34:32

While I think that they were acting with

34:34

the very best of intentions, and

34:36

to an extent, in accordance with

34:38

the best science available at the time, a

34:42

lot of what they did looks to me

34:44

like a mistake in retrospect and would certainly

34:46

be frowned upon socially nowadays. Yeah,

34:49

for sure. In polite

34:51

society at least. Yeah, that's

34:53

right. I think the way

34:56

we talk about weight and

34:58

our appreciation of weight as

35:02

a sensitive issue has just really changed

35:04

since you and I were kids. I'm

35:07

not sure that if this were happening now, I

35:10

don't know if I would be picking on that lever in the

35:12

same way that I did. If it's possible,

35:14

I would. I don't know. That's right. Six-year-old

35:18

Tony is worried he's going to get canceled. Well,

35:22

it's better that we just get this all out right at

35:24

the beginning so

35:27

that if the canceling is going to

35:29

happen, it happens right away. Well,

35:33

let's go ahead and point everyone to your content so

35:35

that they can decide if they want to cancel you.

35:39

Dr. Tony Ragusea makes lots of things for

35:41

public consumption on the Internet. Would you tell

35:43

the people about some of them? I

35:45

mean, I do less of it lately. I've just

35:47

been too busy doing other stuff. But

35:50

yeah, I have on my

35:52

YouTube page, or

35:54

if you go to Facebook and you

35:57

go to Art by Ragusea, that's

35:59

my handle. on Facebook and Instagram. I

36:02

do post a lot of pictures of

36:05

either photography or woodworking that I

36:07

do on my YouTube. Cutting

36:09

boards, if you're listening to

36:12

the Adam Raguciapod, you have a demonstrated elevated

36:15

interest in cutting boards. Yes,

36:17

yes. Dr. Tony makes beautiful cutting boards. I do make a

36:19

lot of cutting boards. Or

36:23

do like drone videography, is lately what I've been doing

36:25

a lot of. But

36:28

on my YouTube page, I've also got some

36:30

old videos trying to teach some very simple

36:32

basics of bonsai, the art

36:34

of bonsai to people who like

36:36

never done anything with bonsai before, trying

36:39

to get, increase their comfort level with the idea. I

36:44

think I may have posted a couple of things on mental health

36:46

topics too. I should do more of

36:48

that. People tell me I should do more of that, but I just, it's

36:51

time consuming. Don't do it.

36:54

But you'll also be in local media

36:56

frequently talking about psychology

36:59

related topics. Yeah. You're in

37:01

the paper a lot. Yeah, I'm in the paper

37:03

a lot. People wanna, sometimes on radio or TV

37:05

or something like that. Yeah,

37:07

and a lot of that is on the internet and findable.

37:10

If you like more of this guy and

37:12

you wanna get some more of him. I

37:15

don't know why you would. I

37:18

just ramble a lot. Well,

37:22

I'm not hunchie like you. Could you, could

37:24

you? No, no, no, no, no, no. You

37:26

were talking off the dome much

37:29

better than I normally do. Like I'm a

37:31

good writer and I'm good at

37:33

delivering written stuff in

37:36

a way that sounds natural and somewhat extemporaneous,

37:38

right? But that's, I'm not, in terms of

37:40

talking off the dome, I'm way, you're way

37:43

cleaner than me. I

37:45

don't know, man. You did that same way

37:47

into the ad like really well. Like that

37:49

was really quick thinking. And this

37:51

is a topic that I think a lot about.

37:53

So like I've been talking about. This is your

37:56

thing. I just like your thing. Yeah, yeah.

37:58

Okay, anything else you wanna. to tell the people

38:00

about it? About

38:03

SSRIs? Yeah, and in

38:05

particular as it applies to kind of diet. I guess the

38:10

takeaway is I

38:12

think that I would have

38:14

given particularly

38:17

to people who wind up being

38:19

on SSRIs for a long time

38:22

because that's that's increasingly common, right?

38:26

The number of people who have been on

38:29

SSRIs for years or

38:31

decades just increases over

38:33

time. And people

38:36

often think that it's because that they like

38:38

they need to be on the medication and

38:40

that may be the case. But

38:42

in my experience oftentimes it's just because

38:45

the primary care doc who is usually

38:47

the one prescribing it just

38:49

hasn't had the time or the skills

38:51

to talk to you about like taking you off of

38:54

it. And you go in for

38:56

a 15-minute med check and they don't

38:58

even need to ask about your your antidepressant or

39:00

they may say, how's your antidepressant going? And you

39:02

say, fine. And they say, all right well let's

39:04

not mess with that. You know if it ain't

39:06

broke don't fix it. So they just

39:08

sort of leave you off. And of course you can't

39:10

cold turkey SSRIs, right? You have to taper off? So

39:13

it gets more risky I

39:15

think at higher doses. It

39:18

gets riskier the longer you've been taking it

39:21

and it gets riskier with certain

39:23

SSRIs like Paxil. It's

39:25

somewhat safer with like

39:28

fluoxetine Prozac which has

39:31

a very very long half-life which

39:33

makes it harder to experience withdrawal symptoms

39:35

from. But again it's very

39:38

hard to predict who will have a

39:40

bad reaction to coming off cold turkey.

39:42

And some people have a hard time

39:44

even with a slow taper, okay?

39:46

This happens very commonly and people

39:49

don't recognize it. And

39:51

they will often like if they come off

39:53

their antidepressant and they start feeling worse or

39:56

if they skip a couple doses and they feel

39:58

a lot worse they'll interpret that as evidence

40:00

that I should be on this medication because I

40:02

feel terrible when I don't take it. And

40:05

they don't realize that what they're experiencing is

40:07

a withdrawal effect from the medication. Yeah, so

40:09

that's important to be aware of. The

40:12

point I was leading to was

40:15

that if you've been on these

40:17

medications for years or decades, understand

40:19

that that's not entirely risk-free. And

40:22

we don't fully understand what the

40:24

impacts of really long-term and antidepressant

40:26

use is on the brain and

40:28

the body. And so

40:30

I tend to discourage people from

40:32

being on these medications longer than they need to.

40:36

Unless you've got a real history

40:38

of recurrent, serious, depressive

40:42

episodes that really do

40:44

clearly benefit from antidepressant treatment, most

40:47

people should not be on antidepressants long-term.

40:52

And one of the risks is what

40:54

you've gone at today, which is the

40:56

weight gain effects of SSR. Like

40:59

I said, it's usually weight gain. And

41:02

the longer that you're on these medications,

41:04

the more that that weight may accumulate.

41:07

And it may be very subtle. Like, it

41:09

may not be obvious what it sounds like

41:11

you're maybe experiencing. It may be pound

41:14

here, pound next week, pound next week, pound

41:16

next week. And so people may

41:18

chart that up to other factors. And it may

41:20

be due to other factors. It may be due

41:22

to Thanksgiving dinner. But it

41:25

could be due to the antidepressant. And

41:27

therefore, if you don't want to be on it, or

41:29

if you have problems with weight gain, and

41:32

you've been on this medication for a really long time and may

41:34

not be off it, you may want to talk to your doc

41:36

about trying to come off of it and

41:39

seeing if that helps your weight issue a

41:41

little bit. You

41:45

know what I really struggle with? Like, I know

41:48

that

41:50

eating less, I feel better. You

41:54

know? Yeah. And I

41:56

know that that is at least partially

41:59

due to... body image issues

42:01

that would be better,

42:04

probably better addressed other ways. You

42:07

know, that's treating the symptom and not the

42:09

cause, right? But

42:11

I also think that, I mean, I

42:13

know how

42:16

much binge

42:18

eating in particular, like binge eating carbs, which is

42:20

a thing that, I don't know if, that's

42:22

the kind of thing that I don't know if you ever

42:24

do. I don't know if Tony Raghousia, like ever

42:27

ate an entire box of milk duds. That doesn't seem

42:29

like the kind of thing you do. You

42:31

know? It's not my MO, but

42:33

I'll tell you, since moving

42:35

back up north, I have,

42:39

because I used to live in Florida, I

42:42

have gained several pounds,

42:45

and it tends to happen in winter,

42:48

when it's like watching TV is like the

42:50

only thing to do. And

42:53

you just wind up out of boredom, just like

42:55

eating lots of pretzels. Okay,

42:57

yeah. So you don't understand this. Fundament,

42:59

I just think that genes, gene

43:02

expression for hedonism or whatever, is much stronger

43:05

in me than it is in you. Yeah,

43:07

yeah, yeah. I definitely agree with that. Yeah,

43:11

and that has been just

43:13

interesting to me, our whole lives. But

43:16

anyway, so the point is that it's

43:18

like, so yes, a pathological behavior, and

43:21

I really wanna distance my remarks from fat

43:23

shaming. I think people should be,

43:26

who they wanna be, what they wanna eat, okay. I'm

43:30

talking about me and my things, okay.

43:32

So for me, what I would identify

43:34

as kind of like a pathological behavior

43:36

is kind of like solitary eating, like

43:39

getting away from people, going upstairs in the dark in

43:41

the night, or going downstairs,

43:43

and then just like piling

43:45

sweet things in. And I know

43:48

that that kind of,

43:51

when you get on, I call it

43:53

the carb train, that's that constant cycle

43:55

of blood sugar spike and influence spike

43:57

and blah, blah, blah, right. this

44:00

like, you know, vicious cycle that

44:02

I know affects me psychologically in

44:04

ways that I feel are beyond

44:06

the body image issues, right? It

44:09

feels like, you know, it's that sort of,

44:11

it might be the inflammatory response is associated

44:14

with eating lots of sugar or, I don't

44:17

know, but I feel as though

44:19

having way too much quick, having

44:21

way too much, my

44:23

blood glucose being high

44:27

makes me cranky or

44:29

maybe it's the ensuing insulin spike,

44:31

right? I

44:35

know it affects my mood and

44:37

therefore, if a drug

44:40

can help me control my appetite and

44:43

therefore avoid those episodes, is

44:46

that not a legitimate psychological

44:48

medication? Ah, oh

44:50

yeah, yeah, we're touching on a

44:52

controversial subject now, aren't we? Yeah?

44:56

Yeah, yeah. I'm not

44:58

telling, you don't have to agree with that,

45:00

but is that not conceivable? I mean, I'm

45:02

not asking you to accept that as an

45:04

axiom, but is that like an arguable position?

45:06

No, yes, and sometimes, yes, that's a right

45:08

to use for that, like in people who

45:10

struggle with, to maintain a high weight. Sometimes,

45:12

they will prescribe this as a right in

45:14

the hopes that it will add to weight

45:16

gain. Yeah. And

45:19

if you have a- It's just agreed, but okay. Right, yeah. And

45:25

yeah, and I mean, is

45:28

it appropriate to

45:31

use antidepressants to regulate weight

45:33

in some way? Is

45:36

it appropriate to use the stimulant- We

45:38

do shit off label all the time. They don't

45:40

even know why I'm trying to work for the

45:42

thing it's prescribed for. Yeah, I, yeah, no, no,

45:44

no, no, I'm not talking about just off label

45:46

use. I'm talking about these kinds of issues like,

45:50

like is it okay to use stimulants

45:52

that are used for ADHD? Is

45:54

it okay for like normal people to take just to

45:56

help them stay up all night to study for an

45:59

exam the next day? Right? Right.

46:02

And I suppose I would argue

46:04

that it's not because

46:06

the healthier way

46:08

to handle that

46:10

problem is to start studying several

46:12

days earlier. And what would benefit

46:14

you is to like work with

46:16

yourself or someone else to like

46:19

not be in a position where you need a

46:21

stimulant in order to do your

46:23

job at night. Whereas what

46:26

I'm, the scenario that I'm like laying

46:28

out is I think categorically different, right?

46:32

You could argue that the better solution to the problem

46:34

is just to get, you know, for me to get

46:36

control over my milk dudding or whatever. And

46:39

I might

46:41

take that on board. On the other hand,

46:44

I would think that like if you compare

46:46

me to the bulk of the human race,

46:48

I am a person of uncommonly high self-control

46:50

already, okay? You know, I'm pretty

46:54

good at like exerting effort, okay? I've

46:58

tried, okay? And

47:00

if I can, and if

47:03

I can eliminate this thing, if I

47:06

can take a pill that will help

47:08

me eliminate this behavior that is hurting

47:10

my body and hurting me psychologically, that

47:13

strikes me as legitimate as long as

47:16

it's not doing me, you know, greater long-term

47:18

harm. And that's

47:20

a big question, right? And we don't need to re-litigate that

47:22

because you just talked about all of the long-term harms of

47:25

these drugs, right? Or potential long-term harms,

47:27

right? Yeah, there's more a lot of

47:30

unknowns, yeah. Okay,

47:32

yeah, no, I think you're making

47:34

a perfectly legitimate point. And

47:38

I also, maybe this is part

47:40

of my broader kind of project to

47:42

try to get the kinds

47:44

of people who would listen to a

47:46

guy like me to be a little

47:48

more open to the incretinimidetic drugs that

47:50

have come out and are, you know,

47:52

causing, you know, how Donald Trump has

47:54

just lost a whole bunch of weight

47:56

with possessing not an ounce of self-control

47:58

in his entire genome. Right? I

48:01

hate that that son of a bitch gets credit for

48:03

his weight loss. All these politicians losing weight because they're

48:05

on $3,000 a month drugs. Oh,

48:08

it pisses me off. But on the other

48:10

hand, I actually am really encouraged

48:13

by the promise of those drugs, and

48:15

I'm dismayed by a lot of the

48:18

fear mongering around them. Like, fucking like

48:20

Sharon Osborn

48:22

gave a quote to CNN, and it's like, now

48:24

it's a CNN story. And forgive me if it's

48:26

not CNN, but it was some other major publication.

48:29

But like Sharon Osborn was just like, I went

48:31

on what's it called? What's the main the famous

48:34

one called? Oh, Zen pick. Oh, Zen pick. Yeah.

48:36

Oh, Zen pick. Yeah. Okay. She

48:38

went on what, you know, probably was probably really

48:40

we govi, but whatever, whatever she was on, and

48:42

she said, like, Oh, the people need to know

48:44

these drugs. Wow, you know, they they're

48:46

very dangerous, because they they I mean, I lost so much

48:49

more weight than I intended to do. And I felt very

48:51

sick to my stomach. And I did not want food at all.

48:53

And I'm just like, Sharon, take

48:57

less. It

49:00

sounds like your dose is too high. Like,

49:03

the hell, your

49:05

complaint is that the drug is working too

49:07

good. Take it less.

49:10

That's not a problem

49:12

with the drug. And

49:14

more profoundly, that is

49:16

not the basis of a

49:18

fucking mainstream news article, cable

49:21

news network, or whichever of you

49:23

committed this crime. A

49:25

celebrity having a complaint about

49:27

a drug is not news.

49:31

Anecdotal reports with this stuff

49:33

are nearly worthless, unless

49:36

they are extremely voluminous. Now

49:38

I am someone who will say that the

49:41

only difference between journalism and science is that

49:43

journalism is quick and dirty and science is

49:45

slow and methodical. Okay. Journalism

49:47

is supposed to be sloppy. Three is

49:49

a trend. Okay, that's a thing. But

49:52

there have to be at least three. There's gotta

49:54

be something it can't just be Sharon Osborne saying

49:56

that she took too much of something. Jesus.

50:00

I just want to point out

50:02

that I think it was you just a few minutes

50:04

ago called me judgy It's

50:08

so it's I mean, I don't know if

50:10

it's because I spent so I like in

50:13

I understand how much of myself I gave

50:16

to that industry and how you know how

50:18

many sacrifices I made and how How

50:21

much I hurt myself going above and beyond

50:23

to try to save

50:25

that godforsaken industry in

50:28

my own little way and yeah,

50:30

like I It

50:35

in so many ways has deserved its

50:37

death, you know, and I and it's

50:39

such a terrible thing for me to say because I I

50:43

especially on the local level I feel that legacy

50:46

journalism and news organizations have

50:49

done immeasurable good in their

50:51

their absence is a travesty

50:53

a catastrophe But

50:57

oh my god Wow

51:00

people's complaints about us were really

51:02

really valid. Oh Jesus

51:04

we were so smug for so long

51:07

about people's core complaints about how we did our

51:09

jobs Like we were bad at

51:11

our jobs. We were just bad at our jobs a

51:15

Lot of the time, you know Adam I think then

51:17

again so then again So is most other people right

51:19

so are most other people everybody half

51:22

the people in any field suck right or

51:24

half the people in any Field are below

51:26

average performance. Oh My definition

51:28

that's an axiom you have to accept

51:30

that as an axiom. That's just statistical

51:32

reality. Yeah, I Think

51:36

I think that we've shown a lot

51:38

of growth today here Adam. Oh, yeah.

51:40

Okay. This session is really good because

51:43

I see you I super coming up on time

51:45

before we started today You

51:48

told me that that you could only talk

51:50

about like one thing at a time which

51:52

was appetite and SSR eyes And

51:55

but now we've talked about two things media

51:59

criticism And SSRIs. So

52:03

I think with practice you might be able to

52:06

entertain more than two things in

52:09

the course of a week. With

52:11

practice, well. Yeah. I'll talk about

52:14

it in the big chair next time. Yeah, yeah. Someone

52:16

other than my brother. Someone other than my brother,

52:18

Dr. Tony Ragusea. Thanks

52:20

for being here. Well, thanks for having

52:22

me. We should do this again sometime. We'll do

52:25

some on like, disordered eating or something like that.

52:29

There's also a bonsai thing we could do. Yeah,

52:31

we could do something bonsai. Because

52:33

there's, well, I'll tell you about it after the call.

52:35

I don't want to. Oh, you

52:37

got your early Christmas present? It's

52:41

the end of the episode, so only the really

52:43

hardcore super fans are listening. So I'll give them

52:45

a preview. Yes,

52:48

this is, I

52:50

don't know how I could do a cooler aquarium than my

52:52

goldfish trough, but I think I've done it. So

52:56

it's a crab habitat that

52:59

imitates a mangrove forest. And

53:03

so I want

53:05

to grow these mangroves bonsai style.

53:08

Oh, cool. I'm going to try to get

53:10

them to try to train them so they kind of

53:12

arch over the rest of the tank and stuff. Interesting.

53:15

I'm excited. I want to see this. I'm

53:17

going to justify doing it on my channel by

53:20

doing a video about rice fish because I'm stocking it

53:22

with rice fish. And rice fish actually are an incredibly

53:24

fascinating topic, but this

53:27

is also so I can make a video about my fish tank. I

53:29

don't blame you. Thanks, Joe. Okay.

53:34

Well, I'll talk to you soon. And

53:38

you, audience, I'll talk to you

53:40

next time, whenever that may be. As

53:44

you can tell, I'm going through some stuff and

53:47

work product may be spotty. And

53:50

I'll just try to communicate with you about that as best

53:52

as I can. Make

53:55

good choices. Talk to you next time.