September 20, 2023 • 16 mins
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Join us this evening for a soiree that will give Bridgerton a run for its money. But not really cause it'll be jiving to the conversation of fluoxetine and fluvoxamine: the twins of SSRIs that never were. Got that warm beverage ready yet for this episode?
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Amayo (00:00):
Do you, Thanh, you guys eat whole fish like that
with the head?
I know some Americans getfreaked out when they see the
head.
Dr. Nguyen (00:06):
My, my mom used to like, try to get me to eat like
the eyeballs of the fish.
No mom, nothing, she, but shewould just be like gnawing on
the head of the fish as well.
And I could never get into it.
Thanh (00:20):
Welcome to the Y in Psychiatry!
Dr. Amayo (00:22):
Hi, this is Dr.
Amayo C/L fellow.
Thanh (00:25):
Where we delve into the intricate nuances of psychiatric
topics.
Dr. Handratta (00:28):
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 (00:38):
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
this journey to unlock themysteries of the human psyche.
(01:02):
Only on The Y in Psychiatry.
Dr. Amayo (01:05):
Welcome back to the Y in psychiatry.
Today we are going to becontinuing our series of
strategy for choosing anantidepressants.
Just to give you a quickreminder, our last episode we
talked aboutcitalopram/escitalopram and
sertraline, and why not tochoose this antidepressants
(01:27):
Today we'll be talking aboutmore antidepressants with
Fluvoxamine, fluoxetine,venlafaxine and duloxetine.
As usual I'm your host, Dr.
Amayo C/L Consultant/LiaisonPsychiatry fellow, and we have
Dr.
V.
Dr. Handratta (01:44):
Hi, this is Dr.
Handratta how are you guysdoing?
Dr. Amayo (01:49):
Alright, so Fluvoxamine is a medication that
I've always stayed away from, Idon't think I've ever prescribed
fluvoxamine.
Seems like it has a lot of sideeffects.
Seems like it's not thateffective.
As a matter of fact, I don'teven think I knew fluvoxamine
was a antidepressant to like mythird year of residency.
So why or why not should we takefluvoxamine?
Dr. Handratta (02:09):
That's a great question.
So a lot of people have noteither heard of fluvoxamine or
they confuse it with Fluoxetineor they've not actually used it
at all, right?
They might have heard of it, butnot gotten an opportunity to use
it.
With my experience and mypractice, I've used fluvoxamine
plenty of times.
And especially I use fluvoxaminea lot in patients who have
(02:29):
obsessive compulsive disorder.
I sometimes combine fluvoxaminewith clozapine, but you have to
be very careful with thatcombination because it can
increase the clozapine level.
We'll talk about that.
So fluvoxamine is an SSRI,right?
But it also actually has a goodpotency towards 5HT3 receptors.
(02:51):
And as we know, 5HT3 receptorsare present in your gut as well
as they're also present in yourchemo receptor trigger zone.
So when you stimulate the 5HT3receptors, you can induce nausea
and vomiting, right?
And we have medications thatblock this receptor, which are
used as antiemetics, likeondansetron, right?
(03:11):
So fluvoxamine can stimulate5HT3.
So the common side effects thatyou see during the first one to
two weeks is headache, nausea,and vomiting, right?
So always tell the patients totake fluvoxamine with food,
right?
But the 5HT3 receptors willdownregulate over a period of
time, like in a week or twoweeks and the side effects will
(03:32):
subside.
Right.
Now fluvoxamine is a greatantidepressant once you start
tolerating it, you have to doseit in the evening.
Because it's sedating, butbecause of the short half-life,
you have to dose it twice a day.
But now you have an extendedrelease formulation of
fluvoxamine, which you can giveonce a day in the evening.
It's an SSRI safe in liverdisease.
(03:53):
You can prescribe it to patientswith cirrhosis.
It is safer in pregnancy.
It's safer in cardiac disease aswell as in renal disease.
It's not the choice in renaldisease.
Renal disease the choice isgoing to be either sertraline or
fluoxetine But the patient hasnot tolerated sertraline or
fluoxetine and you don't haveanything else you can use
fluvoxamine.
And as Dr.
(04:14):
Amayo just mentioned, there's alot of drug interaction.
Three cytochromes (04:17):
cytochrome 1A2, cytochrome 2C19, and
cytochrome 3A4.
So you have to be very carefulwhen you're combining
fluvoxamine in patients who areon a bunch of cardiac
medications, right?
Or they are on a bunch ofanticonvulsants.
(04:38):
Or if they're on a moodstabilizers.
So you have to be a littlecareful.
You have to look at the druginteraction.
I'm not gonna go through eachand every medications that it
interacts with, right?
But something to look for whenyou're prescribing fluvoxamine.
Now there's also a study thatwas done where fluvoxamine is
combined with clozapine toreduce the weight gain by
(05:00):
Clozapine, right because it's aninhibitor of cytochrome 1A2.
It prevents the breakdown ofclozapine to a metabolite called
norclozapine which is consideredto be cytotoxic, which can also
cause weight gain.
But the problem here is that youhave to be very careful and you
need to monitor the clozapinelevel because if you do not
monitor the clozapine level, youcan reach a toxic level of
(05:20):
clozapine and we know whathappens if the clozapine level
is too high, right?
You can actually developagranulocytosis as well as
seizures.
And also keep an eye on acutemyocarditis with the clozapine,
right?
So these are board questions,side effects of clozapine,
right?
Acute myocarditis is somethingthat is commonly missed by
people actually when they are onclozapine.
(05:42):
So you can combine fluvoxaminewith clozapine.
It's an off-label use to preventthe weight gain, but be careful
monitor the clozapine level.
Does it make sense?
Dr. Amayo (05:51):
Makes sense.
A lot to come up withFluvoxamine.
I did not know it was that.
It was that special.
All right, so big highlightshere.
It's a 5HT3 agonist, so you geta lot of headaches and nausea
when you're first starting.
So take with food, take at nightshort acting medication, but
there is a long acting versionof it Inhibit 1A2, 2C19, 3A4.
(06:14):
For that 1A2, you can use it incombination with clozapine to
help reduce the metabolite ofclozapine and hopefully that
would help reduce the weightgain.
But be careful, you mightincrease the level of clozapine.
Good in liver.
I was wondering with all this,with all these reactions with
the CYP enzymes.
Why is it still good with liver?
Dr. Handratta (06:35):
Because it does not go through first pass
metabolism.
Oh plus it doesn't have a toohigh a plasma protein binding.
Okay, so it's much safer.
Dr. Amayo (06:44):
So even though liver doesn't do much with it, it
still affects the enzyme to theliver, but it can be metabolized
and excreted even if you havelower liver function.
And it's safe in pregnancy, nottoo crucial in renal.
Okay.
So those are the highlights forFluvoxamine.
Now let's talk about fluoxetine.
I think Fluoxetine is yourfavorite
Dr. Handratta (07:06):
hahahaha.
Fluoxetine, it's a greatmedication.
I don't use it a lot.
Dr. Amayo (07:12):
Does big pharma pay you for fluoxetine?
Dr. Handratta (07:16):
Fluoxetine is a great medication, don't get me
wrong.
Alright, so the thing withFluoxetine is that it's is a
long halflife, So on one handit's good for patients who are
non-compliant with treatment,right?
But on the other hand it is verydifficult to take the patient
off the fluoxetine and startthem on something that is
(07:37):
inhibited by fluoxetine, right?
So when you're doing a crosstitration, it becomes a little
bit tricky when you're usingfluoxetine.
So let's talk about fluoxetine,right?
I do use fluoxetine.
It's not that I don't use it, Ido use it in younger population
who are not on too manymedications like cardiac
medications or cholesterollowering medications, or
(07:59):
antidiabetic, things like that.
Right now, the biggest advantageof fluoxetine is a long
half-life, right?
It stays in the system so youdon't have to worry about
patients withdrawing when theymiss one or two doses.
In psychiatry, we know thatpatients are non-compliant with
medications, right?
So we never actually ask thepatient, Hey have you been
(08:20):
forgetting your medication?
The best question to ask is weall forget to do things.
How many days in a week have youforgotten or to take your
medication?
That's a better way actually, toput it and the patients will
come forth and say, hey, I'vemissed one or two dose.
And that's very normal, right?
So it's great actually in thatsituation.
Patients are forgettingmedications you cannot prescribe
them fluvoxamine because it is ashort half-lifethen they'll
(08:42):
withdrawal, right?
Or paroxetine.
So that is the biggest advantageof fluoxetine.
The long half life, even afteryou stop the fluoxetine, it
takes five weeks for fluoxetineto be flushed out of the system.
So again, the dose titration,you have to be careful, right?
You have to titrate the doseonce every four weeks because a
(09:03):
steady state takes about fourweeks.
So if you do a very rapidtitration, you can actually
induce toxicity.
Fluoxetine is safer in patientswith renal disease.
So the two antidepressants weprefer is fluoxetine or
sertraline in patients withrenal disease.
In patients with liver disease,you can actually give it, but be
a little careful, It's not likea total contraindication in
(09:26):
patients with liver disease.
Pregnancy (09:28):
you can prescribe fluoxetine patients with
pregnancy, right?
The two plus fluoxetine is alsoconsidered to be safer in
patients who have cardiacdisease.
You can actually give it tothem, but also let's make sure
that you look at the druginteraction.
Okay?
Because it can interact with alot of cardiac medications,
right?
Fluoxetine.
(09:48):
Fluoxetine also inhibits a bunchof cytochromes, okay?
So it can inhibit cytochrome2D6, 2C19 and 3A4 And we know
that a lot of medications aremetabolized by these many
cytochromes, especially 2D6 isinvolved in the metabolism of a
lot of cardiac medication.
So you have to be careful withthat particular interaction.
(10:09):
Be very careful combiningfluoxetine also with a
medication called clopidogrel,right?
Which is basically used incardiac patients as well as
stroke patients.
Because clopidogrel is processedby 2C 19 and Fluoxetine inhibits
it.
So just make sure that you lookat the drug interaction when
you're prescribing fluoxetine.
Dr. Amayo (10:29):
That is it for Fluoxetine.
So Fluoxetine seems like the bigdeal for Fluoxetine is this long
half life.
So take your time when you aretitrating up and take your time
when you're titrating down aswell.
And then, be careful forserotonin toxicity if you're
gonna switch.
Make sure you give enough timefor the fluoxetine, to be out of
the system.
And also another big deal wouldbe the drug interaction.
(10:53):
Seems like it's a potentinhibitor of 2D6, 2C19, 3A4, and
a lot of cardiac medications.
Uses these enzymes, especiallycalled clopidogrel which for it
to be active, it needs to bemetabolized by 2C19.
So if fluoxetine is blockingthis enzyme they might get to a
stage where their platelets arefunctioning too well.
Dr. Handratta (11:14):
And there's one more thing actually, fluoxetine
is that once you hit an 80milligram dosage, the FDA
requires that you get an EKGbecause it can be associated
with QTC prolongation andfluoxetine.
This is a board question forpeople.
It can inhibit its ownmetabolism because fluoxetine is
by cytochrome 2D6.
It inhibits 2D6 so it canactually inhibit its own
(11:36):
metabolism, increasing itsplasma level.
So those are the two things tobe a little bit careful with
fluoxetine.
Dr. Amayo (11:44):
That's good to know.
And so even though it canprolong Q T C, this is not a
problem to you get to 18milligrams.
Yes.
Okay.
I think that's it forFluoxetine.
Alright.
Next we have.
Duloxetine.
This is my favorite medication.
Dr. Handratta (12:03):
Yeah.
So duloxetine is a lot ofpeople's favorite medication,
right?
It's used actually by internalmedicine.
It's used by rheumatology.
It's used by pain medicinepeople.
So it's a very, it's a favoritemedication by a lot of
specialties, right?
So duloxetine is not an SSRI,it's an SNRI, right?
(12:26):
It inhibits serotonintransporter, as well as
norepinephrine transporter.
So it'll increase two differentneurotransmitters.
Now, duloxetine, the one thingto be a little bit cautious
about duloxetine is its shorthalf-life.
So duloxetine, if a patientmisses a dose, they will feel
the side effects by the end ofthe day or the next day, right?
(12:49):
So I always tell the patients,actually keep few pills in your
office drawer so that even ifyou forget to take it at home,
when you're in your office, youhave a prescription, few pills
that you can take to preventbecause the serotonin withdrawal
can be pretty unpleasant.
So that is one thing that I'llbe careful with duloxetine,
because a lot of patients willstop it if they start
experiencing the withdrawalsymptoms, right?
(13:11):
Because a lot of times patientsthink if you have withdrawing,
that means that you'll getaddicted to it.
That's not the situation here.
We'll talk about the definitionof addiction when we talk about
substance use disorder.
So duloxetine, few things aboutduloxetine right?
It's great in patients withmajor depressive disorder.
It also has some off-label uses.
Duloxetine can also be used inpatients who have major
(13:31):
depressive disorder with stressincontinence.
It's not F D A approved for it,but it works in patients with
stress incontinence.
Duloxetine can also be used inpatients with chronic pain who
have depression with chronicpain.
Duloxetine can also be used inpatients with depression, with
fibromyalgia, because patientswith fibromyalgia can have
depression.
(13:52):
Few things about duloxetine youshould be careful in patients
with liver disease.
If patients have liver disease,you should not prescribe
duloxetine to those patients,right?
Patients have renal disease.
You have to be careful actuallyprescribing duloxetine, right?
If the creatinine clearance isless than 30 ml per minute, stop
duloxetine right?
Because it'll cause accumulationof its metabolite that can be
(14:14):
toxic Otherwise it's a greatmedication to be used.
Dr. Amayo (14:17):
But yeah, so duloxetine is a great drug, so
seems like it's a short actingone, so be careful for those
withdrawal.
It's an SNRI.
So it helps with pain, chronicpain, fibromyalgia, neuropathic
pain Be careful with liverdisease and renal disease.
So severely renal disease withcreatine clearance less than 30,
that's when you should probablystop using duloxetine
Dr. Handratta (14:37):
Another thing actually before we end is
duloxetine also be careful withdrug interaction because it's a
moderate cytochrome 2D6inhibitor, so be careful
combining with medication thatis metabolized by 2D6 especially
cardiac medications.
So pay some attention on thedrug interaction when you're
prescribing it.
Dr. Amayo (14:52):
What's QTC prolongation like?
Dr. Handratta (14:54):
The data is patients who have overdose on
duloxetine because it's an SNRIcan cause tachycardia, right?
But the problem with a lot ofthe research article is that
they've used Bazett's formula tocalculate the Q TC interval.
But when you use Bazett's andthe patient has tachycardia,
it'll overcorrect for the QTC.
So you should not use Bazetts's,you should use other uh, formula
(15:16):
for the for calculating the Q TCinterval.
So duloxetine can still be used,just make sure that the patient
doesn't have an underlyingcardiac condition.
But if the patient has anunderlying cardiac condition,
I'll say just get an E K G.
Just for the medical-legalpurpose, right?
You don't have to, but just forthe medical-legal purpose,
monitor the QTC and just monitorthe patients while they're on
(15:36):
duloxetine
Dr. Amayo (15:38):
And that's it for today's episode on the Y in
psychiatry.
Dr. Handratta (15:40):
Thank you guys.
Katrina (15:45):
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.
Do you, Thanh, you guys eat whole fish like that
with the head?
I know some Americans getfreaked out when they see the
head.
Dr. Nguyen (00:06):
My, my mom used to like, try to get me to eat like
the eyeballs of the fish.
No mom, nothing, she, but shewould just be like gnawing on
the head of the fish as well.
And I could never get into it.
Thanh (00:20):
Welcome to the Y in Psychiatry!
Dr. Amayo (00:22):
Hi, this is Dr.
Amayo C/L fellow.
Thanh (00:25):
Where we delve into the intricate nuances of psychiatric
topics.
Dr. Handratta (00:28):
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 (00:38):
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
this journey to unlock themysteries of the human psyche.
(01:02):
Only on The Y in Psychiatry.
Dr. Amayo (01:05):
Welcome back to the Y in psychiatry.
Today we are going to becontinuing our series of
strategy for choosing anantidepressants.
Just to give you a quickreminder, our last episode we
talked aboutcitalopram/escitalopram and
sertraline, and why not tochoose this antidepressants
(01:27):
Today we'll be talking aboutmore antidepressants with
Fluvoxamine, fluoxetine,venlafaxine and duloxetine.
As usual I'm your host, Dr.
Amayo C/L Consultant/LiaisonPsychiatry fellow, and we have
Dr.
V.
Dr. Handratta (01:44):
Hi, this is Dr.
Handratta how are you guysdoing?
Dr. Amayo (01:49):
Alright, so Fluvoxamine is a medication that
I've always stayed away from, Idon't think I've ever prescribed
fluvoxamine.
Seems like it has a lot of sideeffects.
Seems like it's not thateffective.
As a matter of fact, I don'teven think I knew fluvoxamine
was a antidepressant to like mythird year of residency.
So why or why not should we takefluvoxamine?
Dr. Handratta (02:09):
That's a great question.
So a lot of people have noteither heard of fluvoxamine or
they confuse it with Fluoxetineor they've not actually used it
at all, right?
They might have heard of it, butnot gotten an opportunity to use
it.
With my experience and mypractice, I've used fluvoxamine
plenty of times.
And especially I use fluvoxaminea lot in patients who have
(02:29):
obsessive compulsive disorder.
I sometimes combine fluvoxaminewith clozapine, but you have to
be very careful with thatcombination because it can
increase the clozapine level.
We'll talk about that.
So fluvoxamine is an SSRI,right?
But it also actually has a goodpotency towards 5HT3 receptors.
(02:51):
And as we know, 5HT3 receptorsare present in your gut as well
as they're also present in yourchemo receptor trigger zone.
So when you stimulate the 5HT3receptors, you can induce nausea
and vomiting, right?
And we have medications thatblock this receptor, which are
used as antiemetics, likeondansetron, right?
(03:11):
So fluvoxamine can stimulate5HT3.
So the common side effects thatyou see during the first one to
two weeks is headache, nausea,and vomiting, right?
So always tell the patients totake fluvoxamine with food,
right?
But the 5HT3 receptors willdownregulate over a period of
time, like in a week or twoweeks and the side effects will
(03:32):
subside.
Right.
Now fluvoxamine is a greatantidepressant once you start
tolerating it, you have to doseit in the evening.
Because it's sedating, butbecause of the short half-life,
you have to dose it twice a day.
But now you have an extendedrelease formulation of
fluvoxamine, which you can giveonce a day in the evening.
It's an SSRI safe in liverdisease.
(03:53):
You can prescribe it to patientswith cirrhosis.
It is safer in pregnancy.
It's safer in cardiac disease aswell as in renal disease.
It's not the choice in renaldisease.
Renal disease the choice isgoing to be either sertraline or
fluoxetine But the patient hasnot tolerated sertraline or
fluoxetine and you don't haveanything else you can use
fluvoxamine.
And as Dr.
(04:14):
Amayo just mentioned, there's alot of drug interaction.
Three cytochromes (04:17):
cytochrome 1A2, cytochrome 2C19, and
cytochrome 3A4.
So you have to be very carefulwhen you're combining
fluvoxamine in patients who areon a bunch of cardiac
medications, right?
Or they are on a bunch ofanticonvulsants.
(04:38):
Or if they're on a moodstabilizers.
So you have to be a littlecareful.
You have to look at the druginteraction.
I'm not gonna go through eachand every medications that it
interacts with, right?
But something to look for whenyou're prescribing fluvoxamine.
Now there's also a study thatwas done where fluvoxamine is
combined with clozapine toreduce the weight gain by
(05:00):
Clozapine, right because it's aninhibitor of cytochrome 1A2.
It prevents the breakdown ofclozapine to a metabolite called
norclozapine which is consideredto be cytotoxic, which can also
cause weight gain.
But the problem here is that youhave to be very careful and you
need to monitor the clozapinelevel because if you do not
monitor the clozapine level, youcan reach a toxic level of
(05:20):
clozapine and we know whathappens if the clozapine level
is too high, right?
You can actually developagranulocytosis as well as
seizures.
And also keep an eye on acutemyocarditis with the clozapine,
right?
So these are board questions,side effects of clozapine,
right?
Acute myocarditis is somethingthat is commonly missed by
people actually when they are onclozapine.
(05:42):
So you can combine fluvoxaminewith clozapine.
It's an off-label use to preventthe weight gain, but be careful
monitor the clozapine level.
Does it make sense?
Dr. Amayo (05:51):
Makes sense.
A lot to come up withFluvoxamine.
I did not know it was that.
It was that special.
All right, so big highlightshere.
It's a 5HT3 agonist, so you geta lot of headaches and nausea
when you're first starting.
So take with food, take at nightshort acting medication, but
there is a long acting versionof it Inhibit 1A2, 2C19, 3A4.
(06:14):
For that 1A2, you can use it incombination with clozapine to
help reduce the metabolite ofclozapine and hopefully that
would help reduce the weightgain.
But be careful, you mightincrease the level of clozapine.
Good in liver.
I was wondering with all this,with all these reactions with
the CYP enzymes.
Why is it still good with liver?
Dr. Handratta (06:35):
Because it does not go through first pass
metabolism.
Oh plus it doesn't have a toohigh a plasma protein binding.
Okay, so it's much safer.
Dr. Amayo (06:44):
So even though liver doesn't do much with it, it
still affects the enzyme to theliver, but it can be metabolized
and excreted even if you havelower liver function.
And it's safe in pregnancy, nottoo crucial in renal.
Okay.
So those are the highlights forFluvoxamine.
Now let's talk about fluoxetine.
I think Fluoxetine is yourfavorite
Dr. Handratta (07:06):
hahahaha.
Fluoxetine, it's a greatmedication.
I don't use it a lot.
Dr. Amayo (07:12):
Does big pharma pay you for fluoxetine?
Dr. Handratta (07:16):
Fluoxetine is a great medication, don't get me
wrong.
Alright, so the thing withFluoxetine is that it's is a
long halflife, So on one handit's good for patients who are
non-compliant with treatment,right?
But on the other hand it is verydifficult to take the patient
off the fluoxetine and startthem on something that is
(07:37):
inhibited by fluoxetine, right?
So when you're doing a crosstitration, it becomes a little
bit tricky when you're usingfluoxetine.
So let's talk about fluoxetine,right?
I do use fluoxetine.
It's not that I don't use it, Ido use it in younger population
who are not on too manymedications like cardiac
medications or cholesterollowering medications, or
(07:59):
antidiabetic, things like that.
Right now, the biggest advantageof fluoxetine is a long
half-life, right?
It stays in the system so youdon't have to worry about
patients withdrawing when theymiss one or two doses.
In psychiatry, we know thatpatients are non-compliant with
medications, right?
So we never actually ask thepatient, Hey have you been
(08:20):
forgetting your medication?
The best question to ask is weall forget to do things.
How many days in a week have youforgotten or to take your
medication?
That's a better way actually, toput it and the patients will
come forth and say, hey, I'vemissed one or two dose.
And that's very normal, right?
So it's great actually in thatsituation.
Patients are forgettingmedications you cannot prescribe
them fluvoxamine because it is ashort half-lifethen they'll
(08:42):
withdrawal, right?
Or paroxetine.
So that is the biggest advantageof fluoxetine.
The long half life, even afteryou stop the fluoxetine, it
takes five weeks for fluoxetineto be flushed out of the system.
So again, the dose titration,you have to be careful, right?
You have to titrate the doseonce every four weeks because a
(09:03):
steady state takes about fourweeks.
So if you do a very rapidtitration, you can actually
induce toxicity.
Fluoxetine is safer in patientswith renal disease.
So the two antidepressants weprefer is fluoxetine or
sertraline in patients withrenal disease.
In patients with liver disease,you can actually give it, but be
a little careful, It's not likea total contraindication in
(09:26):
patients with liver disease.
Pregnancy (09:28):
you can prescribe fluoxetine patients with
pregnancy, right?
The two plus fluoxetine is alsoconsidered to be safer in
patients who have cardiacdisease.
You can actually give it tothem, but also let's make sure
that you look at the druginteraction.
Okay?
Because it can interact with alot of cardiac medications,
right?
Fluoxetine.
(09:48):
Fluoxetine also inhibits a bunchof cytochromes, okay?
So it can inhibit cytochrome2D6, 2C19 and 3A4 And we know
that a lot of medications aremetabolized by these many
cytochromes, especially 2D6 isinvolved in the metabolism of a
lot of cardiac medication.
So you have to be careful withthat particular interaction.
(10:09):
Be very careful combiningfluoxetine also with a
medication called clopidogrel,right?
Which is basically used incardiac patients as well as
stroke patients.
Because clopidogrel is processedby 2C 19 and Fluoxetine inhibits
it.
So just make sure that you lookat the drug interaction when
you're prescribing fluoxetine.
Dr. Amayo (10:29):
That is it for Fluoxetine.
So Fluoxetine seems like the bigdeal for Fluoxetine is this long
half life.
So take your time when you aretitrating up and take your time
when you're titrating down aswell.
And then, be careful forserotonin toxicity if you're
gonna switch.
Make sure you give enough timefor the fluoxetine, to be out of
the system.
And also another big deal wouldbe the drug interaction.
(10:53):
Seems like it's a potentinhibitor of 2D6, 2C19, 3A4, and
a lot of cardiac medications.
Uses these enzymes, especiallycalled clopidogrel which for it
to be active, it needs to bemetabolized by 2C19.
So if fluoxetine is blockingthis enzyme they might get to a
stage where their platelets arefunctioning too well.
Dr. Handratta (11:14):
And there's one more thing actually, fluoxetine
is that once you hit an 80milligram dosage, the FDA
requires that you get an EKGbecause it can be associated
with QTC prolongation andfluoxetine.
This is a board question forpeople.
It can inhibit its ownmetabolism because fluoxetine is
by cytochrome 2D6.
It inhibits 2D6 so it canactually inhibit its own
(11:36):
metabolism, increasing itsplasma level.
So those are the two things tobe a little bit careful with
fluoxetine.
Dr. Amayo (11:44):
That's good to know.
And so even though it canprolong Q T C, this is not a
problem to you get to 18milligrams.
Yes.
Okay.
I think that's it forFluoxetine.
Alright.
Next we have.
Duloxetine.
This is my favorite medication.
Dr. Handratta (12:03):
Yeah.
So duloxetine is a lot ofpeople's favorite medication,
right?
It's used actually by internalmedicine.
It's used by rheumatology.
It's used by pain medicinepeople.
So it's a very, it's a favoritemedication by a lot of
specialties, right?
So duloxetine is not an SSRI,it's an SNRI, right?
(12:26):
It inhibits serotonintransporter, as well as
norepinephrine transporter.
So it'll increase two differentneurotransmitters.
Now, duloxetine, the one thingto be a little bit cautious
about duloxetine is its shorthalf-life.
So duloxetine, if a patientmisses a dose, they will feel
the side effects by the end ofthe day or the next day, right?
(12:49):
So I always tell the patients,actually keep few pills in your
office drawer so that even ifyou forget to take it at home,
when you're in your office, youhave a prescription, few pills
that you can take to preventbecause the serotonin withdrawal
can be pretty unpleasant.
So that is one thing that I'llbe careful with duloxetine,
because a lot of patients willstop it if they start
experiencing the withdrawalsymptoms, right?
(13:11):
Because a lot of times patientsthink if you have withdrawing,
that means that you'll getaddicted to it.
That's not the situation here.
We'll talk about the definitionof addiction when we talk about
substance use disorder.
So duloxetine, few things aboutduloxetine right?
It's great in patients withmajor depressive disorder.
It also has some off-label uses.
Duloxetine can also be used inpatients who have major
(13:31):
depressive disorder with stressincontinence.
It's not F D A approved for it,but it works in patients with
stress incontinence.
Duloxetine can also be used inpatients with chronic pain who
have depression with chronicpain.
Duloxetine can also be used inpatients with depression, with
fibromyalgia, because patientswith fibromyalgia can have
depression.
(13:52):
Few things about duloxetine youshould be careful in patients
with liver disease.
If patients have liver disease,you should not prescribe
duloxetine to those patients,right?
Patients have renal disease.
You have to be careful actuallyprescribing duloxetine, right?
If the creatinine clearance isless than 30 ml per minute, stop
duloxetine right?
Because it'll cause accumulationof its metabolite that can be
(14:14):
toxic Otherwise it's a greatmedication to be used.
Dr. Amayo (14:17):
But yeah, so duloxetine is a great drug, so
seems like it's a short actingone, so be careful for those
withdrawal.
It's an SNRI.
So it helps with pain, chronicpain, fibromyalgia, neuropathic
pain Be careful with liverdisease and renal disease.
So severely renal disease withcreatine clearance less than 30,
that's when you should probablystop using duloxetine
Dr. Handratta (14:37):
Another thing actually before we end is
duloxetine also be careful withdrug interaction because it's a
moderate cytochrome 2D6inhibitor, so be careful
combining with medication thatis metabolized by 2D6 especially
cardiac medications.
So pay some attention on thedrug interaction when you're
prescribing it.
Dr. Amayo (14:52):
What's QTC prolongation like?
Dr. Handratta (14:54):
The data is patients who have overdose on
duloxetine because it's an SNRIcan cause tachycardia, right?
But the problem with a lot ofthe research article is that
they've used Bazett's formula tocalculate the Q TC interval.
But when you use Bazett's andthe patient has tachycardia,
it'll overcorrect for the QTC.
So you should not use Bazetts's,you should use other uh, formula
(15:16):
for the for calculating the Q TCinterval.
So duloxetine can still be used,just make sure that the patient
doesn't have an underlyingcardiac condition.
But if the patient has anunderlying cardiac condition,
I'll say just get an E K G.
Just for the medical-legalpurpose, right?
You don't have to, but just forthe medical-legal purpose,
monitor the QTC and just monitorthe patients while they're on
(15:36):
duloxetine
Dr. Amayo (15:38):
And that's it for today's episode on the Y in
psychiatry.
Dr. Handratta (15:40):
Thank you guys.
Katrina (15:45):
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.
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