I have no disclosure's.

And we're going to talk about

factors influencing selection of

antidepressants in patients with

complex medical comorbidities.

So yesterday

I actually changed some of the

slides and you'll see why when I get

there. I think it's for a good

reason. And I think you'll

appreciate the change.

We'll see. You may disagree with me

and we'll see, but there are some

changes at the end.

So not at the beginning, though.

John is a 32 year old man who came

in with the first episode of

diagnostic diagnosed four

criteria, major depression.

He has no major medical

comorbidities and no personal or

family history of manic

or hypo manic episodes.

And I should have told you this talk

is sort of a little cases, a little

pearls, some information.

We're just sort of going to guide or

glide around and hopefully learn

some things on the way.

So this is John.

I never see anybody this

straightforward, but if you did,

which antidepressant would you

choose for him?

Prozac, Valiasr Donor hybrid.

That's Venlafaxine Presti Dellucci

18 Cymbalta.

It doesn't matter. I'm too burned

out to care.

OK, so Fluoxetine was the clear

frontrunner.

The correct answer actually is it

doesn't matter.

The second part is also probably

true.

So studies show

that for a population,

every single antidepressant works

equally well to every single other

antidepressant out there.

There is no clear frontrunner.

So if you have somebody like John

walking in and you're right out of

the bat, it doesn't matter which one

you pull out of your pocket.

We'll talk at the end about which

one you might pull out of your

pocket. And by the way, I think

Fluoxetine probably would have been

my choice for John based on

this list. So I think you're

probably thinking what I'm thinking

about that and I'll come back as to

why it would have been.

But it actually doesn't matter if

you're just looking at potential

efficacy for your choice.

So weight gain and antidepressants,

Natasha's 39 years old,

she's got depression, she's morbidly

obese, and she has prediabetes,

she's resistant to taking

antidepressants because she doesn't

want to gain any more weight.

These are the antidepressants least

likely to cause waking up

so and here you might look at

these and think, well, which ones

are generically available

while tolerated, you might make

those kinds of decisions.

But if you have a patient and this

comes up so commonly,

who is worried about taking the

antidepressant for fear of weight

gain? These are going to be your go

to choices. And it's more than just

Wellbutrin, which is the one we tend

to think of.

OK, so this is Jackie.

She's 42 years old.

She has a Cuneen score of 24

consistent with severe clinical

depression.

She has a history of bulimia and

her cutesie is five hundred and

twenty five milliseconds.

So bulimic, very depressed

and prolonged cuchi.

Considering her cutesie, which

of these is the safest

antidepressant choice for her,

Zoloft is out in front.

Bupropion for Stic

is actually your right answer here.

Why does it matter?

All this cutesy stuff is driving

me crazy.

I was so much happier when I didn't

know about it.

And it seems like everybody we see

in the hospital now has a prolonged

cutesie interval and it's just the

bane of my day.

But does it really matter?

The reality is that all the

accessories, all the antidepressants

for most of them and I'm going to

show you the exceptions, do cause

cutesie prolongation, but in about

six milliseconds

is the about the amount that they

prolong it. So it's not a lot

compared to placebo, but it is a

statistically significant

difference.

And that was a comprehensive review

of all of this that showed that, by

and large, there's little evidence

that psychotropic drug use

by itself is sufficient to

predict to Assad

in more than 90 percent of the cases

is at least one additional risk

factor.

And in the cases that did have

to decide, 20 percent

of them actually had a cutesie

less than 500 going into the whole

thing.

And 75 percent of them, the drugs

were at a therapeutic dose.

So a high dose didn't even

predict the tortured.

These were the other risk factors.

So if there's a congenital,

prolonged, cutesie, not

surprisingly, and

you guys are used to looking

at these things as primary care

providers, female hypoglycaemia,

hyperkalemia, bradycardia, a recent

MRI or co administering

cutesie, prolonging medications.

And these.

Absolutely.

I look at it and take care of and

address and ask about

suggests things about all day long,

especially that bottom line, because

we see a lot of transplant patients

and they're on five or seven

different medications that can

prolong the cutesie and looking

at those and trying to figure out

which ones are essential.

And are there alternatives for some

of those, like the antidepressants,

that may not cause acute

prolongation that we could use

instead?

So these are the ones that are

higher risk for causing cutesie

prolongation.

I saw that the least popular choice

of the options there was the North

Tripplehorn, which is a tricyclic

antidepressant.

And you are correct, all of those

do cause cutesie prolongation.

Citalopram, you are probably

familiar with by now, has a black

box warning for cutesie

prolongation, especially at higher

doses.

All of these SSRI also cause

cutesie prolongation, as do

mirtazapine and venlafaxine.

So most of the things you would

reach for right off the bat are

listed here.

These things don't

so Cymbalta or plastic

for Stik was the option I think I

gave you back there or Cymbalta,

either of those or fat similar

do not cause cutesie prolongation.

At all these others do,

but not clinically significant

at therapeutic doses, so vibrant

DRL Wellbutrin or Treinta

Alex.

See some people writing things down,

I'll give you a second to do that.

So in that transplant patient,

for example, a liver transplant

patient.

We'll come back to that second,

we're going to get to that as

another case anyway.

OK, so

if we go back to Jacqui with bulimia

and prolonged cutesie,

which one of the antidepressants is

contraindicated because of her

eating disorder?

Actually, Wellbutrin is

contraindicated for patients with

eating disorders because it lowers

the seizure threshold and increases

the risk of seizures in

that population, specifically

the Mirtazapine or Imuran actually

is the drug of choice many people

treating eating disorders may go to

to help with appetite, stimulation

and weight gain.

But it does not have an FDA

indication that sometimes people

will choose it for that purpose.

Fluoxetine has demonstrated

efficacy and FDA approval

for the treatment of bulimia.

There are no antidepressants that

have an FDA indication for the

treatment of anorexia.

So I'm throwing some pearls and in

some cases.

Guiding along, driving along here,

OK, pharmacogenomics,

LeBron has been diagnosed with major

depression, he's read that

genetic testing can help you pick

the medication. That's right for

him.

Regarding pharmacogenetic testing,

all of the following are true except

so which one of these is not true?

It'll help you determine which

medications your patient

metabolizes, normally more quickly

or less rapidly than normal.

It can help predict medication

tolerance.

It can help predict medications that

will not be helpful.

It will predict which medication is

most likely to benefit the patient.

And all of these are actually true.

You get a double negative going on

there. So just go with the last.

All of these would be true.

OK, so actually the answer

is D.

The pharmacogenetic testing will not

predict which medicine is going to

most likely benefit the patient

if you take a person who has normal

pharmacogenetics.

They're going to respond to whatever

antidepressants that you give them

based on just their clinical

response.

How can I phrase this, because this

does get confusing for folks, it

will tell you what they're

metabolizing and how they're

metabolizing it, a is is

pretty clear.

It can help predict medication

tolerance. So if patients have

if they're poor metabolism of 2006,

for example, so they're tricyclic

antidepressants are going to start

back up and backing up and backing

up and their tricyclic level is

going to go up. We're going to have

lower tolerance so that medication

somebody else would tolerate at the

same dose, it's going to predict

that.

It may predict which ones are not

going to be helpful because they're

metabolizing them too quickly.

So they're rapid, ultra rapid

metabolism or something.

So they're never going to get to a

therapeutic drug or

level, but it's not actually going

to tell you. It's going to say which

ones are metabolizing, but it's not.

We'll tell you whether that was

going to work for them.

It's just going to tell you if

they've got Skari metabolism or that

medication.

I phrased it can help predict

versus it will predict.

It's very subtle, but it will not

predict actually which medication

will be the medication that helps

any more than I could have

predicted.

Paxil is going to work for you and

Prozac is going to work for you and

Vibert is going to work for you.

There's no test is going to tell me

which one is going to work.

That makes sense.

Or if I can just confused everybody.

We'll go on as though I didn't

confuse everybody.

OK?

Gerard has end stage liver disease

and is listed for transplant,

which of the following is

contraindicated for Gerard?

Wellbutrin, Cymbalta, Zoloft,

Effexor, plastic.

So actually, the one that is

contraindicated for Jerrard with

advanced liver disease is Dulac

Sateen.

It's contraindicated in patients

with advanced liver disease,

so Jerrard is still Jarrard,

we didn't pick Cymbalta.

So we need a medicine that has

minimal hepatic metabolism,

it might be a really good choice for

him. Which of these has the least

hepatic metabolism going

to be a really good choice for a

patient with advanced stage liver

disease?

All right, so very evenly divided,

though, among the choices, I mean,

it was very good that you didn't go

to that's what I was thinking,

but bupropion, sertraline

and des Venlafaxine

were equal runners, very equal.

And the correct answer actually is

Des Venlafaxine has

very minimal hepatic metabolism

and is one of its

real neches is in patients with

very advanced liver disease.

With prolonged Kutty interval, it

turns out to be, I'm not pushing

that medicine, it just happens to be

the.

Well, you think?

We've taken care of those folks,

maybe I should try one of the new

antidepressant medications, what's

one? Should I pull out one of those?

And these are the newest ones.

Until just recently, Vibert

came out in 2011 26,

2013, and Fitzsimon 2013.

So Vibert is an SSRI,

but also a partial serotonin

agonist.

That's his sort of niche, has a high

rate of gastrointestinal side

effects, but its niche

is in patients with

with major depression and comorbid

generalized anxiety disorder.

So consider that for anxious,

depressed patients.

Keeping in mind that none of these

work any better than the others, so

the other SSRI also have FDA

indications for the treatment of

generalized anxiety disorder.

And I know of no particular

study that's showing that this is

better at that. But if you're

looking for when would I use this,

I would think about this situation.

26 or 40 Occitan,

the mechanisms not really well

understood, is sort of playing

poker at the serotonin receptor

and lauded several different ways.

It's Nitsch maybe that

there were some findings that it may

improve cognitive functioning in

patients with major depression that

was independent of his

antidepressant effect.

I'm truly kind of trying to find you

a niche for these for these

medications, when would you go for

this one rather than another one?

And this was a finding that came

from this study.

And Leavel Marzipan, which is

Fitzsimon, is an enantiomer,

M.A. Sopranos, Savelli, which is

approved, as you know, for

fibromyalgia, SAVOLA

did not have any does not have

an FDA indication or proven efficacy

for the treatment of major

depression.

But this enantiomer

does.

It's a potent SSRI

and because it's an NRI,

the nor nor adrenergic

reuptake inhibition increases

motivation and energy.

So that's going to be true of any

norepinephrine medication.

So I can't say that it's unique to

this one, but that may be a niche

for it if you're looking for a

reason to use it.

High incidence of nausea as well

with this one.

So there's similar efficacy between

all of those, and I've already said

that. So sexual dysfunction,

James is a 23 year old.

He's coming in with sexual

dysfunction from the SSRI you

prescribed for him.

What?

These are the antidepressants

associated with minimal sexual

dysfunction, Wellbutrin is probably

the one that's going to come to your

mind first and foremost.

But Vibert and Intellichoice also

have no sexual dysfunction

or none were found in the studies.

Mirtazapine is one that we will

sometimes try and patients who are

having sexual dysfunction associated

with their antidepressants.

It does seem better

than the others, but there is a risk

of it as well.

These are probably true.

Goto's keeping in mind again

that this is generic and these may

be very expensive for your patient.

This is generic.

So here, here's the changes I made

that are

so Rick Santillan, who's

heard of this, Rick Santorum

just scattering.

OK, well, this is why I'm telling

you about this, because this was

just approved three days ago.

For postpartum depression,

it will be released sometime

in May. It looks like it

is a synthetic alow pregnant

alone, which is the

the metabolite

of progesterone.

It's Agaba, a receptor

Alistaire modulator.

It works within 48 hours

of infusion.

It requires 60 hours

of continuous infusion in

the medical setting.

Its main side effects are dizziness

and syncope.

It only requires one treatment of 60

hours in the medical setting,

but that one treatment costs thirty

four thousand dollars.

For the drug.

That does not include the cost of

being in the hospital or

the doctors or any of that stuff.

And does anybody have any idea what

it cost to be in the hospital for a

day?

Any idea?

How many?

33000 per day.

My God,

I was thinking maybe five,

wow, so that adds up

quickly.

It is FDA approved.

Women did find that suicidal

thoughts started clearing as early

as 24 to 36

hours after starting the infusion.

Thiers progesterone rises

during pregnancy plummets at the

time of delivery.

And that's one of the thoughts as to

what's triggering postpartum

depression.

And it works.

So it's gotten FDA indication,

but it's 34000.

There is a formulation similar

to this compound that's being

developed for oral administration is

not yet available, but it's in the

pipeline.

So that may be coming out.

But this is just very much

off the presses and just available

as of three are just approved

by the FDA as of three days ago.

Then there's S.

S ketamine's bravado,

and it's the first and and this was

just approved two weeks ago,

it's the first and only NMDA

receptor antagonist and it's

approved as an adjunct to other

antidepressant medications for

treatment resistant depression.

So you keep taking your oral

medication and

you're using this spray.

So ketamine,

this was after the 300 viewing

of Lamees,

so ketamine was a horse tranquilizer

is a picture of the horse.

It is a party drug nicknamed a

Special K

that gives people dissociative,

floating, kind of out of it kind of

experience, can have psychotic

side effects with it.

That's ketamine, ketamine was first

studied in 1964 on

prisoners in this

compound, later named ketamine.

It became approved by

the FDA in 1975 as

an anesthetic.

And in 2000, studies started

to be done around its use as an

antidepressant.

It is as as as is

ketamine and NMDA receptor

antagonist, it has

a rapid onset antidepressant

effect within hours, sometimes

within 30 minutes,

people's depression will clear.

It's really amazing.

There's something here is working on

the glutamate receptor, something

novel and different about

the way this is working and very

promising about the future in

treating depression.

And it works even for treatment

resistant depression.

So there were studies that have also

been shown that it works very

quickly and very effectively for

suicidality patients coming

into a psychiatric emergency room,

given a single infusion of

point, five milligrams per kilogram,

intravenous ketamine had resolution

of their suicidality within 40

minutes.

So this bravado, this is ketamine

is an S and antima of

ketamine itself.

It was approved on March the 5th

of this year and became

available.

Three days ago

can now be prescribed.

The dosing is 56 to 84

milligrams, and you start with 56

and it's not a response the next

time you do 80 for

it's approved for treatment

resistant depression.

And that's defined as patients who

failed at least two antidepressant

trials used at adequate

doses for an adequate duration

of time, which is usually defined as

six weeks.

The the administration of it is

twice a week for four weeks, then

you go weekly for four weeks

and then you can go every one

or two weeks thereafter, usually

go to every two weeks thereafter.

But some patients need it more.

And then there's the punch line,

six hundred and nine hundred dollars

per session.

For the medicine.

Not including the cost of the doctor

and the visit and all of that stuff.

Its side effects are dissociation,

dizziness, nausea.

You can read them there.

I'll let you read.

So another catches, you can't drive

for 24 hours after you've taken the

medication, so if you're getting

it twice a week, that's four days

a week that you can't drive.

There's restricted distribution

system, so only certain pharmacies

will be able to get it.

They have to sign up and register to

be part of it.

There is a special risk evaluation

and mitigation strategy program,

just like there is for Clozaril and

some other medications that are high

risk. And that's because this is a

drug of abuse.

That's why I had the special case

slide up there.

People get high off of ketamine

and using high doses and this is

just a little spray thing.

You can only get so much out of it

and you get to have one little

thing. You spray once and then five

minutes later you spray again.

And that's all there is to the whole

kit. So you're not going to get very

far with that little kid if you were

to steal it or get it.

But if you had a lot of it

somewhere, you'd have a lot of

street value and people would really

want it. It was very highly

controlled.

It does have to be administered

in a physician's office or hospital,

and they have to have at least two

hours of monitoring by

a health care professional before

they can go home because of the risk

of dissociation, because of the risk

of treatment, emergent psychosis,

hypertension, the other side effects

I showed you.

So it's not without risk.

It has amazing potential,

very powerful benefit,

but it has its issues.

So let me close with just talking

about general considerations when

choosing an antidepressant,

and we're going back to that first

guy whose name I forget

where he was at, no medical

history, no bipolar history, any of

that stuff where how do you choose

antidepressants for people in

general?

So which side effects do

you want or not don't want?

Do you want this patient to gain

weight?

Do you when you might use

mirtazapine, do you want them to not

gain weight? So you might use

Wellbutrin or Villazon?

Do you want to sedate them so

you may use Mirtazapine

or do you want to activate them and

give them some energy?

So in essence, Arri or some of the

less sedating ones

is sexual dysfunction.

One of the considerations that

you're looking at

and what gave you the list of those

that don't cause sexual dysfunction

is their liver disease, comorbid

liver disease, liver kidney

problems, metabolism,

drug interactions, all of that

stuff.

Does that patient have a personal

history of taking something and

responding to it?

That's your choice.

If they do, I took Prozac

before and it did great and I

stopped it. Why do you stop it?

Because I was better.

Well, let's go back to that.

And if they tolerated it.

Is there a family history of

response so this guy's coming in for

the first time, he's never seen an

antidepressant, but everybody in his

family's had major depression and

they've all responded to whatever it

was, whatever it was

is is where you're going to go

cost.

So is it generically available?

So Prozac is about three dollars

a month. Fluoxetine was your first

choice there, generically available?

Very well. Tolerate is one of the

best tolerated of the antidepressant

medications.

Doesn't tend to be sedating.

It's one of two or three that are

approved by the FAA for pilots

to take.

I think it was a great choice you

made right off the bat.

If you had to choose one from that

list. There are a lot of things

going forward that made it a

reasonable first choice.

I'm not plugging that medication.

They all work equally well to each

other, but just looking for factors.

And when would you choose one

if the patient does have a known

pharmacogenetic profile that's going

to guide you. So if now he's walking

in and for whatever reason

he paid 23 and me or somebody or

he has his pharmacogenetic profile

in front of you, it's never been on

an antidepressant.

And he's a two desex poor

metabolism, which is

how Prozac is metabolized

Fluoxetine.

I'm not going to go with that

medication because I already know

he's not going to metabolize it

well, or if he's an ultra rapid

metabolism that I know, I could go

with that and really crank up the

dose or I could just use something

from a different pathway that's not

going to get in my way.

And does the patient have a

preference?

My Aunt Mildred took this whatever

it was, and she really liked it, or

I hate the name of that or I

still oh, I mean, seriously,

nineteen. I trained in nineteen

and early 1990s and that's

when Prozac came out, was like late

eighties. And there was this whole

Prozac hysteria at that time that

Prozac was making people go crazy

and they were killing people, they

were killing themselves.

And this whole thing, that was never

true and it was proven to not

be true.

But still to this day, people who

were not even born at that time

looking at tell me, I don't want to

take Prozac. I've heard about it and

it's just not true.

But the patient may have a

preference in a way that may or may

not have any validity.

But go with that. Listen to what

they want.

Thank you so much for your

attention.