July 12, 2023 • 14 mins
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On this episode, we will continue our antidepressant journey and find out what the buzz around ketamine is all about. Hear Dr. Miracle and Dr. Hendratta discuss the use of ketamine in the treatment of depression. Explore everything from its receptors in the brain, why it works so fast, and why psychiatrists may be turning to this in their everyday practice. Tune in to find out what’s so special about Special K.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Handratta (00:00):
One is called reward seeking behavior.
(00:01):
Okay.
Where you actually run towardsthe reward.
Another one is called miseryfleeing behavior that you run
away from misery.
That is towards safety.
Dr. Amayo (00:09):
That's, that's my baseline.
Dr. Handratta (00:10):
Yes.
That's baseline.
Thanh (00:14):
Welcome to the Y in Psychiatry,
Dr. Amayo (00:16):
Hi, this is Dr.
Amayo C/L fellow.
Thanh (00:20):
Where we delve into the intricate nuances of psychiatric
topics
Dr. Handratta (00:23):
My name is Dr.
handratta attendingpsychiatrist.
I did my residency fromUniversity of Connecticut and
then I did my fellowship fromGeorgetown University in
consultation and liaison.
Thanh (00:33):
Each episode features interview style discussions that
explore the intersection of themind medicine and the human
experience.
Together we'll uncover thehidden why and the
groundbreaking discovery shapingthe psychiatric landscape.
So grab a seat, warm beverage,tune in, and let's embark on
(00:53):
this journey to unlock themysteries of the human psyche.
Only on The Y in Psychiatry.
Dr. Amayo (01:01):
So welcome back to the Y in psychiatry.
It is your host, Dr.
Amayo.
I also go by Miracle.
I'm a consultant liaison fellow,and as usual my co-host, Dr.
Handratta, is here with us.
Today we have a treat.
We are going to be talking aboutspecial K, and by that I mean
(01:21):
ketamine.
It's one of the newerantidepressants uh, out here on
the market and its been having alot of press a lot of, fanfare
and today we're and, uh, Dr.
Handratta, I just want to start,I just want to start simple.
Dr. Handratta (01:37):
Before we talk about ketamine, the definition I
want to clarify is treatmentresistant depression because
that's where we commonly useketamine is when patients have
treatment-resistant depression.
So what does it mean?
So there are differentdefinitions but the one that is
widely accepted is when apatient has failed two different
(02:01):
antidepressants that belong totwo different class prescribed
at an adequate therapeuticdosage, and for an adequate.
Duration of time, right?
So if they have failed two ofthem at a therapeutic dosage and
tried for the duration of time,that is about eight to 12 weeks.
(02:23):
Then we say that the patient hastreatment resistant depression.
So when patients actually havetreatment resistant depression,
that's when we usually thinkabout, Alternative treatment for
depression and one of thealternative treatment that has
been proved to be prettybeneficial in treatment
resistant depression is a use ofketamine.
Dr. Amayo (02:42):
Sounds like ketamine is the best, why aren't we just
giving it out there?
Why are we waiting fortreatment-resistant depression
to use it?
What should we be concernedabout?
Dr. Handratta (02:51):
So as we know, ketamine is always given in
association with a conventionalantidepressants.
Yeah.
You just do not give ketaminejust by itself.
The patient is also on anotherconventional antidepressants,
right?
The problem with ketamine is itsabuse potential.
So Ketamine is used as ananesthetic as well as an
(03:11):
analgesic agent.
Yeah.
So there is a huge abusepotential, especially of IV
ketamine.
And that's why it's actually notused as a first line treatment
for depression.
And saying is true actually forIV ketamine as well as the
intranasal esketamine.
Yeah, sure.
Dr. Amayo (03:30):
Okay, so mainly the abuse potential.
So can patients get addicted toketamine treatment?
Yes.
Is that correct?
Okay.
Dr. Handratta (03:38):
Yes, they can get addicted to ketamine treatment.
Plus you cannot give ketamine athome because a lot of patients
do in the first 60 minutes willdissociate.
And that is a reason whenever apatient comes to the ketamine
clinic, they're alwaysaccompanied by a family member.
They're not supposed to driveactually, after the treatment,
somebody actually has to takethem home.
Yeah.
(03:59):
So there is quite a good amountof risk using ketamine or
esketamine as a first linetreatment and to be used at
home.
Dr. Amayo (04:06):
And I know that there's also a concern or a
contraindication for psychosis.
Possible to worsen psychosis?
Do we know how that works?
Is it because we dissociate?
Dr. Handratta (04:18):
So some of the research data have actually
shown that the functionalconnectivity between the
thalamus as well as thehippocampus and the thalamus and
the prefrontal cortex isresponsible for the psychotic
symptoms we see when ketamine isgiven, right?
Because there's a disconnectionbetween the thalamus and the
hippocampus and thalamus and theprefrontal cortex in patients
with schizophrenia.
(04:39):
Right, we know that throughdifferent research data, some
people who actually have apredisposition for psychosis,
because of this impactfunctional connectivity between
the thalamus and the prefrontalcortex, thalamus, hippocampus
are more prone for psychosisthan they're introduced to
ketamine.
Dr. Amayo (04:57):
How does Ketamine help?
Dr. Handratta (04:58):
So in short and simple language, ketamine is an
NMDA receptor antagonist, and ithas an agonist property at AMPA
receptors.
So both are receptors that areacted on by glutamate.
So these are ionotropicreceptors.
Dr. Amayo (05:21):
And AMPA is also a glutamate receptor, so it's a
agonist on AMPA and as well, anantagonist on NMDA, which is
another glutamate receptor.
Is that correct?
Dr. Handratta (05:34):
That's right.
Dr. Amayo (05:35):
Oh wow.
Dr. Handratta (05:38):
So the way ketamine works is, so let's go
back to the pyramidal neurons aswell as the GABA interneurons.
So our prefrontal cortex is richin GABA interneurons, and as we
mentioned previously, GABAinterneurons are responsible for
fine tuning of the pyramidalneurons, which are glutaminergic
(06:01):
in nature.
So the way ketamine works is itbasically blocks the NMDA
receptors on these GABA interneurons.
So when you block the NMDAreceptors on the GABA
interneurons, you decrease therelease of GABA.
(06:22):
Your prefrontal cortex, apartfrom the pyramidal neurons that
it has, it also hasglutaminergic input coming into
the prefrontal cortex.
One of the glutaminergic inputthat comes into the prefrontal
cortex is from the thalamus.
Another one is from thehippocampus and so on, right?
So all these neurons that entersinto the prefrontal cortex, they
(06:43):
are rich in GABA a receptors.
So when you block the NMDAreceptor on the GABA inter
neuron, you disinhibit theseincoming pyramidal neurons.
Okay?
So you basically increase therelease of glutamate from the
presynaptic glutaminergicpyramidal neurons Does it make
sense so far?
Dr. Amayo (07:04):
Yes.
Yes.
So the prefrontal cortex, haslots of pyramidal neurons, which
is a mainly glutaminergicneurons, and then this pyramidal
neurons has the GABAinterneurons, which act as a
break for them, slows down theglutaminergic neurons.
Now, ketamine blocks the GABAinterneurons, which increases
(07:25):
glutamate by the pyramidalneurons.
Dr. Handratta (07:29):
Exactly.
So by inhibiting the GABAinterneurons, you basically
disinhibit the incomingglutaminergic connection into
the prefrontal cortex.
Dr. Amayo (07:40):
So is it mainly the glutaminergic connection from
the thalamus and the hippocampusthat we are targeting?
Dr. Handratta (07:47):
So those are some of the examples of incoming
neurons into the prefrontalcortex.
Okay.
Then you have the post-synapticpyramidal neurons in the
prefrontal cortex.
And these pyramidal neurons willhave NMDA receptors and AMPA
receptors because glutamate hasto act on the prefrontal cortex
(08:07):
pyramidal neurons.
Right Now, as we mentioned,ketamine blocks the NMDA
receptors.
So what ketamine will do is thatit'll block the NMDA receptors
on the prefrontal cortex,pyramidal neurons.
One of the downstream effect ofblocking these NMDA receptor is
increasing BDNF (08:25):
that is brain-derived neurotropic
factors.
And there is also an increase insomething called mTOR, which is
mammalian target of rapamycin.
So the overall effect ofincreasing BDNF, an mTOR that is
target of rapamycin is tostimulate the process of
(08:48):
synaptogenesis that isincreasing the number of
dendritic spines on thesepyramidal neurons so that they
can actually be more active.
Does it make sense?
Dr. Amayo (09:01):
And I have more connection?
Yes.
Makes sense.
Dr. Handratta (09:04):
Right now, this is one mechanism of action of
ketamine.
Now, ketamine is also brokendown into a metabolite called as
hydroxynorketamine.
This hydroxynorketamine is anagonist on the AMPA receptors.
Dr. Amayo (09:22):
So this is how it affects the AMPA receptors
through its metabolites.
Dr. Handratta (09:26):
Exactly.
And when you stimulate the AMPAreceptor, the downstream effect
is the same.
It basically increases the BDNFas well as the target of
rapomycin.
Dr. Amayo (09:37):
Yeah, as well as mTOR and our regular antidepressants,
our regular SSRIs does havesimilar effects, similar
downstream effect to increaseBDNF.
What makes ketamine, betterduring this?
Is it because of the dual actionwith the AMPA receptors?
Dr. Handratta (09:54):
That's a great question.
So why does ketamine work fasterthan conventional
antidepressants?
Now the way most of theantidepressants work, whether it
be ECT or it be SSRIs, SNRIs,NDRIs, or ketamines is by
increasing BDNF and is brainderived neurotropic factors.
Dr. Amayo (10:17):
Okay.
Dr. Handratta (10:18):
What conventional antidepressants do is that they
basically help in the process ofneurogenesis in the hippocampus,
right?
Because research work has shownthat there's a decrease in the
volume of hippocampus inpatients with depression.
Especially an area of thehippocampus called dentate
gyrus.
(10:38):
So conventional antidepressantswill stimulate the neurogenesis
in the hippocampus.
In the hippocampus there is anarea called dentate gyrus where
you have progenitor stem cells.
All right.
What antidepressant does is thatit stimulates the stem cells so
that the stem cells then developinto immature granule neurons
(10:59):
finally become a mature neurons.
So this entire process ofneurogenesis takes weeks.
So this is one of the theory whyconventional antidepressant
takes weeks to show the benefit.
Dr. Amayo (11:11):
Sure.
Fact, 70%.
Yes.
Dr. Handratta (11:15):
On the other hand, what Ketamine actually
does is that it acts directly onthese immature granule neurons,
which are called as the adultborn immature granule neurons.
So that is the reason whyketamine works faster as
compared to the conventionalantidepressant because of its
(11:37):
direct effect on these immaturegranule neurons.
Dr. Amayo (11:41):
Wow.
And do we know what it doesdirectly to these immature
granule neurons?
Dr. Handratta (11:48):
So when you stimulate the immature granule
neurons, so these immaturegranule neurons are rich in NMDA
and AMPA receptors.
So when you stimulate them, whatit does is that it increases the
synaptic connection between thehippocampus and the prefrontal
cortex.
Okay.
So it increases thecommunication between the two,
which is which is the hypothesisthat is responsible for the
(12:10):
antidepressant effect
Dr. Amayo (12:11):
Yeah, the antidepressant effects.
That, that makes sense.
And before I ask my lastquestion on ketamine, I just
wanna summarize.
So Ketamine is used fortreatment resistant depression,
which is a failure of twoantidepressant.
Ketamine works by antagonizingNMDA glutamate receptors and is
an agonist of AMPA glutamatereceptors.
(12:33):
Now this, doing this has adownstream effect of one
increasing BDNF, which promotesthe BDNF and mTOR, which
promotes and stimulatessynaptogenesis so causing more
neuron connections.
And then ketamine has an addedbenefit of itself working
directly to the immature granuleneurons, which are basically
(12:54):
progenitor cells in the dentategyrus of the hippocampus.
And as we're doing this again,increases the synaptogenesis and
increases the connection betweenthe hippocampus and the
prefrontal cortex, and in a way,this is similar to how other
antidepressant works.
Ketamine is just very good andbetter at doing it.
Okay.
And just one last question onthat.
(13:15):
So so does ketamine widen thatgap between the thalamus and the
prefrontal cortex when it'sgiven in these patients?
Dr. Handratta (13:24):
Yeah.
It's basically like thedisconnection between the
thalamus and the hippocampus andthe thalamus and the prefrontal
cortex predisposes thesepatients more to psychotic
features.
Because ketamine is an NMDAreceptor antagonist.
And patients with schizophrenia,they have hypofunctioning NMDA
receptors.
Okay.
So when you block an NMDAreceptor in susceptible
individuals, you increase therisk of psychosis.
Dr. Amayo (13:46):
Let's save it for our psychotic episode, but that
makes sense.
And so, ketamine, the things tobe concerned for is abuse
potential, its possibility tocause dissociation, and for
patients that are predisposed topsychosis, it increases the risk
of developing psychosis.
That's enough for this episode.
Thank you for listening.
Dr. Handratta (14:06):
Thank you, Dr.
Amayo.
Katrina (14:11):
Thank you for joining us on today's episode.
Our tireless team is alreadyhard at work, cobbling together
another potpourri of fascinatingdiscussion for next week, so be
sure to tune in, visit ourwebsite and our podcast feed and
let us know your thoughts on theepisode.
Subscribe so you don't miss ourreleases every Wednesday.
Until next time, keep smiling,keep shining, and stay curious.
One is called reward seeking behavior.
(00:01):
Okay.
Where you actually run towardsthe reward.
Another one is called miseryfleeing behavior that you run
away from misery.
That is towards safety.
Dr. Amayo (00:09):
That's, that's my baseline.
Dr. Handratta (00:10):
Yes.
That's baseline.
Thanh (00:14):
Welcome to the Y in Psychiatry,
Dr. Amayo (00:16):
Hi, this is Dr.
Amayo C/L fellow.
Thanh (00:20):
Where we delve into the intricate nuances of psychiatric
topics
Dr. Handratta (00:23):
My name is Dr.
handratta attendingpsychiatrist.
I did my residency fromUniversity of Connecticut and
then I did my fellowship fromGeorgetown University in
consultation and liaison.
Thanh (00:33):
Each episode features interview style discussions that
explore the intersection of themind medicine and the human
experience.
Together we'll uncover thehidden why and the
groundbreaking discovery shapingthe psychiatric landscape.
So grab a seat, warm beverage,tune in, and let's embark on
(00:53):
this journey to unlock themysteries of the human psyche.
Only on The Y in Psychiatry.
Dr. Amayo (01:01):
So welcome back to the Y in psychiatry.
It is your host, Dr.
Amayo.
I also go by Miracle.
I'm a consultant liaison fellow,and as usual my co-host, Dr.
Handratta, is here with us.
Today we have a treat.
We are going to be talking aboutspecial K, and by that I mean
(01:21):
ketamine.
It's one of the newerantidepressants uh, out here on
the market and its been having alot of press a lot of, fanfare
and today we're and, uh, Dr.
Handratta, I just want to start,I just want to start simple.
Dr. Handratta (01:37):
Before we talk about ketamine, the definition I
want to clarify is treatmentresistant depression because
that's where we commonly useketamine is when patients have
treatment-resistant depression.
So what does it mean?
So there are differentdefinitions but the one that is
widely accepted is when apatient has failed two different
(02:01):
antidepressants that belong totwo different class prescribed
at an adequate therapeuticdosage, and for an adequate.
Duration of time, right?
So if they have failed two ofthem at a therapeutic dosage and
tried for the duration of time,that is about eight to 12 weeks.
(02:23):
Then we say that the patient hastreatment resistant depression.
So when patients actually havetreatment resistant depression,
that's when we usually thinkabout, Alternative treatment for
depression and one of thealternative treatment that has
been proved to be prettybeneficial in treatment
resistant depression is a use ofketamine.
Dr. Amayo (02:42):
Sounds like ketamine is the best, why aren't we just
giving it out there?
Why are we waiting fortreatment-resistant depression
to use it?
What should we be concernedabout?
Dr. Handratta (02:51):
So as we know, ketamine is always given in
association with a conventionalantidepressants.
Yeah.
You just do not give ketaminejust by itself.
The patient is also on anotherconventional antidepressants,
right?
The problem with ketamine is itsabuse potential.
So Ketamine is used as ananesthetic as well as an
(03:11):
analgesic agent.
Yeah.
So there is a huge abusepotential, especially of IV
ketamine.
And that's why it's actually notused as a first line treatment
for depression.
And saying is true actually forIV ketamine as well as the
intranasal esketamine.
Yeah, sure.
Dr. Amayo (03:30):
Okay, so mainly the abuse potential.
So can patients get addicted toketamine treatment?
Yes.
Is that correct?
Okay.
Dr. Handratta (03:38):
Yes, they can get addicted to ketamine treatment.
Plus you cannot give ketamine athome because a lot of patients
do in the first 60 minutes willdissociate.
And that is a reason whenever apatient comes to the ketamine
clinic, they're alwaysaccompanied by a family member.
They're not supposed to driveactually, after the treatment,
somebody actually has to takethem home.
Yeah.
(03:59):
So there is quite a good amountof risk using ketamine or
esketamine as a first linetreatment and to be used at
home.
Dr. Amayo (04:06):
And I know that there's also a concern or a
contraindication for psychosis.
Possible to worsen psychosis?
Do we know how that works?
Is it because we dissociate?
Dr. Handratta (04:18):
So some of the research data have actually
shown that the functionalconnectivity between the
thalamus as well as thehippocampus and the thalamus and
the prefrontal cortex isresponsible for the psychotic
symptoms we see when ketamine isgiven, right?
Because there's a disconnectionbetween the thalamus and the
hippocampus and thalamus and theprefrontal cortex in patients
with schizophrenia.
(04:39):
Right, we know that throughdifferent research data, some
people who actually have apredisposition for psychosis,
because of this impactfunctional connectivity between
the thalamus and the prefrontalcortex, thalamus, hippocampus
are more prone for psychosisthan they're introduced to
ketamine.
Dr. Amayo (04:57):
How does Ketamine help?
Dr. Handratta (04:58):
So in short and simple language, ketamine is an
NMDA receptor antagonist, and ithas an agonist property at AMPA
receptors.
So both are receptors that areacted on by glutamate.
So these are ionotropicreceptors.
Dr. Amayo (05:21):
And AMPA is also a glutamate receptor, so it's a
agonist on AMPA and as well, anantagonist on NMDA, which is
another glutamate receptor.
Is that correct?
Dr. Handratta (05:34):
That's right.
Dr. Amayo (05:35):
Oh wow.
Dr. Handratta (05:38):
So the way ketamine works is, so let's go
back to the pyramidal neurons aswell as the GABA interneurons.
So our prefrontal cortex is richin GABA interneurons, and as we
mentioned previously, GABAinterneurons are responsible for
fine tuning of the pyramidalneurons, which are glutaminergic
(06:01):
in nature.
So the way ketamine works is itbasically blocks the NMDA
receptors on these GABA interneurons.
So when you block the NMDAreceptors on the GABA
interneurons, you decrease therelease of GABA.
(06:22):
Your prefrontal cortex, apartfrom the pyramidal neurons that
it has, it also hasglutaminergic input coming into
the prefrontal cortex.
One of the glutaminergic inputthat comes into the prefrontal
cortex is from the thalamus.
Another one is from thehippocampus and so on, right?
So all these neurons that entersinto the prefrontal cortex, they
(06:43):
are rich in GABA a receptors.
So when you block the NMDAreceptor on the GABA inter
neuron, you disinhibit theseincoming pyramidal neurons.
Okay?
So you basically increase therelease of glutamate from the
presynaptic glutaminergicpyramidal neurons Does it make
sense so far?
Dr. Amayo (07:04):
Yes.
Yes.
So the prefrontal cortex, haslots of pyramidal neurons, which
is a mainly glutaminergicneurons, and then this pyramidal
neurons has the GABAinterneurons, which act as a
break for them, slows down theglutaminergic neurons.
Now, ketamine blocks the GABAinterneurons, which increases
(07:25):
glutamate by the pyramidalneurons.
Dr. Handratta (07:29):
Exactly.
So by inhibiting the GABAinterneurons, you basically
disinhibit the incomingglutaminergic connection into
the prefrontal cortex.
Dr. Amayo (07:40):
So is it mainly the glutaminergic connection from
the thalamus and the hippocampusthat we are targeting?
Dr. Handratta (07:47):
So those are some of the examples of incoming
neurons into the prefrontalcortex.
Okay.
Then you have the post-synapticpyramidal neurons in the
prefrontal cortex.
And these pyramidal neurons willhave NMDA receptors and AMPA
receptors because glutamate hasto act on the prefrontal cortex
(08:07):
pyramidal neurons.
Right Now, as we mentioned,ketamine blocks the NMDA
receptors.
So what ketamine will do is thatit'll block the NMDA receptors
on the prefrontal cortex,pyramidal neurons.
One of the downstream effect ofblocking these NMDA receptor is
increasing BDNF (08:25):
that is brain-derived neurotropic
factors.
And there is also an increase insomething called mTOR, which is
mammalian target of rapamycin.
So the overall effect ofincreasing BDNF, an mTOR that is
target of rapamycin is tostimulate the process of
(08:48):
synaptogenesis that isincreasing the number of
dendritic spines on thesepyramidal neurons so that they
can actually be more active.
Does it make sense?
Dr. Amayo (09:01):
And I have more connection?
Yes.
Makes sense.
Dr. Handratta (09:04):
Right now, this is one mechanism of action of
ketamine.
Now, ketamine is also brokendown into a metabolite called as
hydroxynorketamine.
This hydroxynorketamine is anagonist on the AMPA receptors.
Dr. Amayo (09:22):
So this is how it affects the AMPA receptors
through its metabolites.
Dr. Handratta (09:26):
Exactly.
And when you stimulate the AMPAreceptor, the downstream effect
is the same.
It basically increases the BDNFas well as the target of
rapomycin.
Dr. Amayo (09:37):
Yeah, as well as mTOR and our regular antidepressants,
our regular SSRIs does havesimilar effects, similar
downstream effect to increaseBDNF.
What makes ketamine, betterduring this?
Is it because of the dual actionwith the AMPA receptors?
Dr. Handratta (09:54):
That's a great question.
So why does ketamine work fasterthan conventional
antidepressants?
Now the way most of theantidepressants work, whether it
be ECT or it be SSRIs, SNRIs,NDRIs, or ketamines is by
increasing BDNF and is brainderived neurotropic factors.
Dr. Amayo (10:17):
Okay.
Dr. Handratta (10:18):
What conventional antidepressants do is that they
basically help in the process ofneurogenesis in the hippocampus,
right?
Because research work has shownthat there's a decrease in the
volume of hippocampus inpatients with depression.
Especially an area of thehippocampus called dentate
gyrus.
(10:38):
So conventional antidepressantswill stimulate the neurogenesis
in the hippocampus.
In the hippocampus there is anarea called dentate gyrus where
you have progenitor stem cells.
All right.
What antidepressant does is thatit stimulates the stem cells so
that the stem cells then developinto immature granule neurons
(10:59):
finally become a mature neurons.
So this entire process ofneurogenesis takes weeks.
So this is one of the theory whyconventional antidepressant
takes weeks to show the benefit.
Dr. Amayo (11:11):
Sure.
Fact, 70%.
Yes.
Dr. Handratta (11:15):
On the other hand, what Ketamine actually
does is that it acts directly onthese immature granule neurons,
which are called as the adultborn immature granule neurons.
So that is the reason whyketamine works faster as
compared to the conventionalantidepressant because of its
(11:37):
direct effect on these immaturegranule neurons.
Dr. Amayo (11:41):
Wow.
And do we know what it doesdirectly to these immature
granule neurons?
Dr. Handratta (11:48):
So when you stimulate the immature granule
neurons, so these immaturegranule neurons are rich in NMDA
and AMPA receptors.
So when you stimulate them, whatit does is that it increases the
synaptic connection between thehippocampus and the prefrontal
cortex.
Okay.
So it increases thecommunication between the two,
which is which is the hypothesisthat is responsible for the
(12:10):
antidepressant effect
Dr. Amayo (12:11):
Yeah, the antidepressant effects.
That, that makes sense.
And before I ask my lastquestion on ketamine, I just
wanna summarize.
So Ketamine is used fortreatment resistant depression,
which is a failure of twoantidepressant.
Ketamine works by antagonizingNMDA glutamate receptors and is
an agonist of AMPA glutamatereceptors.
(12:33):
Now this, doing this has adownstream effect of one
increasing BDNF, which promotesthe BDNF and mTOR, which
promotes and stimulatessynaptogenesis so causing more
neuron connections.
And then ketamine has an addedbenefit of itself working
directly to the immature granuleneurons, which are basically
(12:54):
progenitor cells in the dentategyrus of the hippocampus.
And as we're doing this again,increases the synaptogenesis and
increases the connection betweenthe hippocampus and the
prefrontal cortex, and in a way,this is similar to how other
antidepressant works.
Ketamine is just very good andbetter at doing it.
Okay.
And just one last question onthat.
(13:15):
So so does ketamine widen thatgap between the thalamus and the
prefrontal cortex when it'sgiven in these patients?
Dr. Handratta (13:24):
Yeah.
It's basically like thedisconnection between the
thalamus and the hippocampus andthe thalamus and the prefrontal
cortex predisposes thesepatients more to psychotic
features.
Because ketamine is an NMDAreceptor antagonist.
And patients with schizophrenia,they have hypofunctioning NMDA
receptors.
Okay.
So when you block an NMDAreceptor in susceptible
individuals, you increase therisk of psychosis.
Dr. Amayo (13:46):
Let's save it for our psychotic episode, but that
makes sense.
And so, ketamine, the things tobe concerned for is abuse
potential, its possibility tocause dissociation, and for
patients that are predisposed topsychosis, it increases the risk
of developing psychosis.
That's enough for this episode.
Thank you for listening.
Dr. Handratta (14:06):
Thank you, Dr.
Amayo.
Katrina (14:11):
Thank you for joining us on today's episode.
Our tireless team is alreadyhard at work, cobbling together
another potpourri of fascinatingdiscussion for next week, so be
sure to tune in, visit ourwebsite and our podcast feed and
let us know your thoughts on theepisode.
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