Understanding Clozapine: Dr Syl Explains WHAT YOU NEED TO KNOW

Summary

This video delves into the complex nature of clozapine, an antipsychotic medication, highlighting its efficacy in treating treatment-resistant schizophrenia. It discusses the drug's history, including a period of market withdrawal due to severe side effects like agranulocytosis. The speaker outlines the drug's indications, its pharmacological mechanisms, and the critical side effects, emphasizing the importance of stringent monitoring. Despite the potential for serious side effects like neutropenia and myocarditis, clozapine's effectiveness in reducing psychosis, aggression, and suicidal tendencies is underscored, with a call for balanced risk assessment and patient autonomy in treatment decisions.

Takeaways

• 💊 Clozapine is a highly effective antipsychotic medication, particularly for treatment-resistant schizophrenia.
• ⚠️ Clozapine carries significant side effects, including rare but serious conditions like neutropenia and agranulocytosis, necessitating strict monitoring.
• 📈 The drug was withdrawn from the market due to deaths from agranulocytosis but was reintroduced with stringent monitoring protocols.
• 🏥 Initiation of clozapine typically occurs in a hospital setting to allow for gradual dose escalation and intensive monitoring.
• 🧪 Regular blood tests are essential for early detection of potentially life-threatening side effects, with the frequency of testing easing after 18 weeks.
• 🌐 The use of clozapine varies widely across countries, with some having more stringent monitoring requirements than others.
• 🧠 Clozapine's mechanism of action is not fully understood, but it is known to bind to various neurotransmitter receptors, including dopamine and serotonin.
• 🤔 The drug is also indicated for treatment-resistant mania, suicidality, and aggressive behavior, as well as certain conditions like autism spectrum disorder.
• 💤 Common side effects of clozapine include hypersalivation, sedation, and significant weight gain, which require management strategies.
• 🏋️‍♂️ Patients on clozapine must adopt a healthy lifestyle with regular exercise and a balanced diet to counteract weight gain and other metabolic effects.

Q & A

What is the primary focus of the video script?

The primary focus of the video script is to discuss Clozapine, an antipsychotic medication, covering its benefits, side effects, history, indications for use, pharmacology, and the monitoring requirements associated with its use.

What is the significance of the patient story involving Mr. AB?

The patient story involving Mr. AB is significant as it illustrates a real-life example of how Clozapine can be effectively used in treating treatment-resistant schizophrenia, highlighting its positive impact on patients who do not respond well to other antipsychotic medications.

Why was Clozapine temporarily taken off the market?

Clozapine was temporarily taken off the market due to cases of agranulocytosis, a condition where white blood cell count drops significantly, leading to immunocompromise and, in severe cases, death from infections.

What are the indications for using Clozapine according to the script?

According to the script, Clozapine is indicated for treatment-resistant schizophrenia, treatment-resistant mania, reducing suicidal tendencies in psychotic illnesses, and in some cases, for aggressive behaviors and psychotic depression.

How does Clozapine work, and why is its mechanism of action considered complex?

Clozapine works by binding to various receptors, including dopamine (D1, D4), serotonin, and others, with a unique 'hit and run' mechanism. Its mechanism is considered complex because it does not strongly bind to the D2 receptor, which is typically associated with reducing psychosis, and it also has immunomodulatory properties, affecting the immune system response in the brain.

What are the rare but serious side effects of Clozapine that require stringent monitoring?

The rare but serious side effects of Clozapine that require stringent monitoring are neutropenia and agranulocytosis, which involve a decrease in neutrophil count, potentially leading to life-threatening infections, and myocarditis, which is inflammation of the heart muscles.

Why is it important to monitor for fever while on Clozapine?

Monitoring for fever while on Clozapine is important because fever can be an early sign of myocarditis or neutropenia, both of which are serious side effects. Early detection through regular blood tests and medical review can prevent severe complications.

What are some common side effects of Clozapine mentioned in the script?

Common side effects of Clozapine mentioned in the script include hypersalivation, sedation, and weight gain. These side effects can impact patient compliance and quality of life, requiring management strategies such as medication adjustments or lifestyle changes.

How often are blood tests required when starting Clozapine, and why?

When starting Clozapine, blood tests are required weekly for 18 weeks to closely monitor for the rare but serious side effects like neutropenia and myocarditis. After 18 weeks, the frequency of blood tests can be reduced to monthly because the risk of these side effects significantly decreases.

What is the significance of the monitoring protocol for Clozapine, and why is compliance crucial?

The monitoring protocol for Clozapine is significant because it helps to identify and manage serious side effects early, ensuring patient safety. Compliance is crucial because missing doses or failing to follow the monitoring schedule can lead to a loss of the medication's benefits and an increased risk of side effects. Missing Clozapine for 72 hours requires restarting the entire monitoring process.

Outlines

00:00

💊 Introduction to Clozapine's Dual Nature

The paragraph introduces the topic of Clozapine, an antipsychotic medication, highlighting its effectiveness for treatment-resistant schizophrenia but also foreshadowing its complex side effects. The speaker outlines the video's structure, which includes a patient story, historical context, indications for use, pharmacology, and a detailed discussion on side effects and monitoring requirements. The speaker aims to make the content accessible to a broad audience, including non-medical professionals.

05:00

📚 Historical Overview and Effectiveness of Clozapine

This section delves into the history of Clozapine, from its discovery in the 1950s to its temporary withdrawal from the market due to agranulocytosis, a severe side effect. The speaker discusses the reintroduction of Clozapine in the 1990s with strict monitoring requirements and emphasizes its high efficacy, particularly in treatment-resistant schizophrenia. The paragraph also touches on the variability in Clozapine usage across different countries.

10:03

🧬 Pharmacological Insights and Indications

The speaker explores the pharmacology of Clozapine, explaining its receptor binding profile and its unique 'hit and run' mechanism. Clozapine's broader binding to various receptors is suggested as a reason for its reduced extrapyramidal symptoms compared to other antipsychotics. The paragraph outlines Clozapine's indications, including treatment-resistant schizophrenia, mania, suicidality, aggression, and certain conditions like autism spectrum disorder and psychotic depression.

15:03

⚠️ Navigating Clozapine's Side Effects

A detailed examination of Clozapine's side effects is presented, distinguishing between common and rare but serious effects. Neutropenia and agranulocytosis are highlighted as rare yet critical side effects, with an explanation of their mechanisms involving the clozapine molecule's interaction with neutrophils. The paragraph also mentions myocarditis as another serious side effect, emphasizing the importance of regular blood tests and medical monitoring.

20:03

🩺 Monitoring and Management Strategies

The paragraph discusses the rigorous monitoring process required for patients on Clozapine, including initial blood tests, ECGs, and echocardiograms. The speaker outlines the frequency of blood tests, which are weekly for the first 18 weeks and then monthly, and the importance of compliance to avoid restarting the monitoring process. The paragraph also addresses common side effects like hypersalivation, sedation, and weight gain, offering practical advice for management.

25:04

🌟 Conclusion on Clozapine's Utility and Caution

In conclusion, the speaker reiterates Clozapine's effectiveness for patients unresponsive to other antipsychotics, advocating for its use while emphasizing the importance of adherence to the medication regimen. The speaker encourages viewers to consult with healthcare professionals before starting Clozapine and to maintain open communication with their medical team to manage potential side effects effectively.

Keywords

💡Clozapine

Clozapine is an atypical antipsychotic medication primarily used for treatment-resistant schizophrenia. It is highlighted in the video as an 'incredible drug' with complex pharmacology and significant efficacy for patients unresponsive to other antipsychotic treatments. The script discusses its history, side effects, and the importance of monitoring, emphasizing its role as a last-resort medication for severe psychiatric conditions.

💡Neutropenia

Neutropenia refers to a low count of neutrophils, a type of white blood cell crucial for immune defense. In the context of the video, it is a rare but serious side effect of clozapine that can lead to immunocompromise and potentially life-threatening infections. The video underscores the importance of regular blood tests to monitor for this condition, reflecting the drug's need for stringent monitoring.

💡Agranulocytosis

Agranulocytosis is a severe reduction in all types of granulocytes, including neutrophils, which can result from clozapine use. It is mentioned in the video as a historical reason for clozapine being taken off the market in some countries due to deaths associated with this condition. The video discusses the reintroduction of clozapine with strict monitoring protocols to mitigate this risk.

💡Pharmacology

Pharmacology is the study of how drugs interact with biological systems. The video touches upon clozapine's pharmacology, noting its complex mechanism of action involving multiple neurotransmitter receptors. This includes binding to dopamine, serotonin, and other receptors, which contributes to its effectiveness but also its side effects.

💡Schizophrenia

Schizophrenia is a chronic mental disorder characterized by hallucinations, delusions, and disorganized thinking. The video uses the term to describe the primary condition for which clozapine is prescribed, especially in cases where other antipsychotic medications have failed.

💡Myocarditis

Myocarditis is inflammation of the heart muscle, which is another rare but serious side effect of clozapine discussed in the video. It emphasizes the need for regular medical monitoring, including ECGs, to detect this condition early.

💡Hypersalivation

Hypersalivation, or excessive saliva production, is a common side effect of clozapine mentioned in the video. It can cause discomfort and is an example of the less severe but still impactful side effects that patients may experience, affecting their quality of life and medication adherence.

💡Sedation

Sedation refers to the drowsiness or reduced alertness that can be a side effect of antipsychotic medications like clozapine. The video discusses strategies to manage this side effect, such as adjusting the dosage or timing of medication, to improve patient compliance and comfort.

💡Weight Gain

Weight gain is a common side effect of many antipsychotic drugs, including clozapine. The video warns that clozapine can lead to significant weight gain if not managed with a healthy diet and regular exercise, which is crucial for maintaining overall health and reducing the risk of associated conditions like diabetes.

💡Extrapyramidal Symptoms (EPS)

EPS are movement disorders that can occur as a side effect of some antipsychotic medications. The video notes that clozapine has a lower risk of causing EPS compared to other antipsychotics, which can be an important consideration for patients who have experienced these side effects with other medications.

Highlights

Clozapine is an effective drug for treatment-resistant schizophrenia.

The video discusses the complex nature of clozapine, including its history and side effects.

Clozapine was taken off the market due to agranulocytosis-related deaths but was reintroduced with strict monitoring.

Mr. AB's patient story illustrates the effectiveness of clozapine in treating resistant psychosis.

Clozapine's use is indicated for treatment-resistant schizophrenia, mania, and suicidal behaviors.

The pharmacology of clozapine is not fully understood, but it is known to bind to various receptors.

Clozapine reduces positive symptoms of psychosis, such as hallucinations and delusions.

It also helps with negative symptoms like lack of motivation and emotional blunting.

Clozapine has anti-aggressive and anti-suicidal properties, making it valuable for certain patient populations.

The side effects of clozapine include common issues like hypersalivation and sedation.

Rare but serious side effects include neutropenia and myocarditis, requiring intensive monitoring.

Weight gain is a common side effect of clozapine, necessitating a commitment to a healthy lifestyle.

Starting clozapine involves a gradual dose increase and intensive monitoring, often as an inpatient.

Compliance with clozapine is crucial; missing doses can require restarting the monitoring process.

The video concludes that clozapine is a life-changing medicine for those unresponsive to other treatments.

The presenter emphasizes the importance of discussing clozapine with a doctor before starting treatment.

Transcripts

so yes I've been telling you how good

cause of pain is but now it's time to

tell you uh the not so good side of

clozapine in this video we're going to

talk about all things clozapine an

incredible drug with some side effects

we need to know about very complex drug

uh so let's get into it so the outline

of this video will have five parts the

first is a bit of a patient story to

give you an example of how you commonly

see clonazepine being used the second is

we'll talk just a touch about the

history of cause of pain because it's

pretty interesting uh given the fact

that it was actually taken off the

market at one point uh we'll talk about

the indications for its use the

chemistry and the pharmacology around

how it works or at least how we think it

works you know there's still a lot to be

discovered about the human brain and

finally the most important thing for

patients and people who are educating

people around clozapine the most

important thing to know is the side

effects and the monitoring requirements

for those side effects a quick note this

will probably be a level of maybe a

junior maybe a senior medical student

Junior doctor but I will try and make it

useful for everyone even if you're not

in the medical field or not a medical

professional so with that being said

let's get into it

so let's start with a bit of a patient

story

um this is kind of made up an

amalgamation of different patients I've

seen uh over the years uh they kind of

give an example of how good cause of

pain is so let's just call this guy Mr a

b uh he's 40

um and he has a diagnosis of

schizophrenia when he was 20 years old

when he was 20 he was found wandering a

skate park at 2AM in the morning

completely disorganized this is after

months and months of socially being

withdrawn from his family and friends uh

and police picked him up and he just

made no sense when he was speaking which

is what we call loosening of

associations it's an example of

disordered thought form which is a sign

of psychosis and he was diagnosed with

his first episode psychosis since then

he had tried after that lanzapine or

piprazole combinations of antipsychotics

and nothing really worked for him he

kept coming back to hospital with

disorganized thought and uh and saying

things that didn't make sense and and

and sometimes you know behaving

dangerously like punching walls or

running on the streets in the middle of

the night and into traffic so it can be

really dangerous being psychotic

obviously so finally he goes into

hospital and they start him on clozapine

because it one of the indications which

we will go through is treatment

resistance schizophrenia and because he

had recurrent psychosis he had accrued

the diagnosis of schizophrenia but once

he started Clozapine he hadn't he ever

since he started Cosby and he hadn't

gone back to hospital ever since it

worked really really well it's the best

he's ever been then six years later he

developed something called neutropenia

which is one of the side effects we're

going to talk about and how to stop

cause of pain all right let's stop the

patient's story there and talk about

clozapine so over the past week I had to

give a presentation and I had to go

through a lot of different papers to

talk about uh clozapine but part of it

is I learned a bit about the history

which was very interesting it was

discovered by Wonder Pharmaceuticals in

the 50s and it was kind of brought into

the market 60s and 70s and it was

working really really well but then they

kind of noticed people dying from

something called a granulocytosis which

is essentially when a specific type of

white blood cell so it was a little bit

of a memory jogger your blood is got

water proteins fats and cells in it and

it's got red blood cells and white blood

cells red blood cells do the oxygen

white blood cells do the the immune

system defense there are a lot of

different types of white blood cells but

they can be kind of grouped into the

agranulocytes and the granulocytes and

and the differentiation is actually

completely based off microscopy and how

they look under a microscope not based

on function but the granulocytes are the

things that look like they have granules

like stones or dots under a microscope

and one of those there's like three or

four granulocytes but one of them is the

neutrophil and this is the cell that

gets affected by clozapine in a very

small percentage of people you know less

than one percent uh and uh unfortunately

in Finland they they found nine people

who died because they lacked this white

blood cell and obviously if you don't

have that white blood cell you're

immunocompromised right it's an immune

cell so if you don't have it you're

immunocompromised and these people were

dying from infections so the whole

entire world except for like poor

countries that like didn't really uh

have strict monitoring requirements so

develop open countries such as India

were kept using close pain but most of

the entire world pulled closet paint off

of the market because of the risks and

then they had no clozapine for a decade

and everyone was pretty unwell there was

so many people that just were not

responding to any other psychotics and

so in the 90s there was a couple of

studies that just showed how effective

uh cozipine is over the Alternatives

like chlorpromazine there's a big study

by Canada and uh and so it was

reintroduced but you had to do very

strict monitoring so that you wouldn't

get the agranulocytosis it was to kind

of pick up on agranulocytosis before you

got the symptoms of an infection and

then you would become really unwell so

with the monitoring it reduced the

incidence and the death rate or the

morbidity the the you know the illness

rate of getting sick with

agranulocytosis substantially and ever

since it's been a wonderful drug there's

so much variability in the world like

there are some countries that are so

I mean I gotta say it they're scared of

using it unfairly uh so uh you know the

percentage of people who have

schizophrenia who are on clozapine

ranges from like four percent in the

United States to like 40 in other

countries like Australia so that's a bit

about the history now let's talk a bit

about the indication why would people

ever need to use clozapine well

um the kind of agreed upon International

indication because there are differences

in different countries for when they use

clozapine but the one thing that all

countries agree upon is that it's useful

in treatment resistant schizophrenia

okay so it's when you have a psychotic

chronic psychotic illness that isn't

responding to the other antipsychotics

and just to give you an example of how

effective it is I just will quote this

paper despite non-response to other

antipsychotics the chance of responding

to clozapine is more than 60 percent so

that is saying that if you have failed

two other antipsychotics with a chronic

psychotic illness you have a two out of

three chance of having some response

with clozapine and you know half of

those will have a substantially positive

response so it's a very freaking

effective medicine now there are other

indications for clozapine um you know

and it's always treatment resistant so

treatment resistant Mania you can use

clozapine it's useful for people who are

very suicidal with their illness because

it's got evidence to suggest that it

reduces suicide especially in psychotic

illness it also reduces violence so

people who are very violent uh and

behaviorally aggressive so for example

it's in some countries it's actually

indicated for autism spectrum disorder

for people who suffer from autism who

are just so unwell that they get violent

and then the final indication as well

which kind of falls under psychosis

slash mood a psychotic depression so

people who are so depressed that they've

actually developed a psychosis now in

terms of how it works the pharmacology

now don't click away if you don't

understand any of this stuff because if

you're a patient or okay Giver you need

to listen to the next part which is the

monitoring and the side effects but in

terms of how it works look it's

incompletely understood we know which

receptors it binds to which is very

interesting but it's kind of unexpected

that it works as well as it does based

on those receptors because what we

expect is if people are really psychotic

that when you block a receptor called

the D2 receptor it reduces The psychosis

but what we see with clozapine is that

it actually doesn't bind that strongly

to that receptor it it seems to do this

other thing though it seems to bind on

and off like a hit and run mechanism

where it binds and like it binds and

releases binds and releases really

really quickly so that might be how it

has its effect

um but the the it binds stronger to the

D1 the D4 receptors and and not even

only on the D receptors which stand for

dopamine receptors but it also blocks

serotonin receptors which is the

thinking around why it has less movement

side effects because in case you didn't

know there's other antipsychotics that

have movement side effects they're

called extrapyramidal symptoms

and for the medical students watching it

you've got to know these it's the tart

of dyskinesia parkinsonism with the

hypertonia and the cogwheeling where

they feel stiff as a board the dystonia

uh you know when the with the muscle

spasm and the akathesia the need to move

the inner restlessness so those are the

kind of common

symptoms that you don't get with

clozapine that you might get with other

antipsychotics and it also binds to a

bunch a bunch of other receptors so name

your neurotransmitter it can probably

bind to that receptor so it has

glutaminergic activity anti-cholinergic

activity but also some cholinergic

activity it also has nmda receptor

properties and one thing I don't really

understand in much depth is it has

immunomoduly modularity properties so it

actually affects your immune system

response in the brain that's a bit

Beyond me but the point is we don't

fully understand how it works we just

know it works really really well the key

things it does that works well is it

reduces psychotic positive symptoms so

things like auditory hallucinations

hearing voices hearing mumbling hearing

command hallucinations telling you to do

things it reduces delusions so people

having fixed and false beliefs like

they're being followed like someone's

gonna kill them in the next minute like

they're being or like they've got uh you

know chips implanted in their heads and

they're monitoring their thoughts and

things like that it also works pretty

well for the negative symptoms which a

lot of other antipsychotics don't do

like don't really uh touch on because

they're really hard to treat negative

symptoms if you haven't heard of

negative symptoms these are the symptoms

of psychosis where there's an absence of

of things absence of motivation absence

of thought so literally they'll just

have empty thought times and people can

just sit and lie in bed all day these

are some of the negative symptoms you

see so causing help a little bit with

that and other than the antipsychotic

elements of it it's anti-aggressive and

anti-suicidal all right aggressions kind

of angered towards the outside and

society and suicidal behaviors kind of

anger towards the inside so it reduces

suicide in people who have treatment

resistant schizophrenia and treatment

resistant depression and all those

things I mentioned before but it comes

at a price and so yes I've been telling

you how good cause of pain is but now

it's time to tell you uh the not so good

side of cause of pain positan has side

effects yes because it's so effective it

comes with side effects and they can be

split into two categories the the common

ones and the really rare ones but the

really rare ones can be life-threatening

if they're not picked up on early and

that is why there is very stringent

intensive monitoring when you start

clozapine at the end of the video we'll

talk about what it's like to start cause

of pain but for now I'm just going to

talk through all of the different uh

side effects that you need to know and

so the most famous One rare as it is but

life-threatening if it occurs is

neutropenia and agranulocytosis those

two words are kind of on a spectrum and

what it means is the neutrophil count

goes down now why does it happen

I I think I'm just gonna geek out right

now and go full science here so so you

don't need to understand this but I only

learned about this uh this week and it

and I a lot of other doctors don't know

about this so it's really cool let's

let's do the science so if you actually

look at this screen on Wikipedia you can

um see the clozapine molecule here now

how does this is the clozapine molecule

how does cosmen get metabolized the

medical students you should know this

it's the

sip1a2 enzyme in hepatocytes so it's in

the liver the liver metabolizes

clozapine and what does sip1a2 do it

demethylates it removes a methyl group

CH4 so this is just two ways that it's

um you know this this is the same cause

I've been structure just one's an

animation one's a line structure so it

removes this group here okay it removes

these four here that's a carbon and

three hydrogens when that gets removed

there is a moment of time where there's

nothing there except for the electrons

in this Bond right so there's a free

electron pair it's a valence elect it's

a valence electron pair so they have

um they're very reactive and so what

happens is you get a nitranium ion where

you have basically free electrons that

will bind to anything that's around and

the thinking here is that they bind to

proteins or something in neutrophils

that damages the neutrophils and kill

the neutrophils it's either that they're

called cause direct toxicity through

denaturing proteins or something very

important in neutrophils or that they

cause a haptin mediated immune response

so a haptin this is again this is for

the med students what happened is when

the

protein or or you know chemical like

clozapine binds to a antibody and then

it is expressed on the cell surface and

mediates a cell mediated cytotoxic

response type 4 hypersensitivity

reaction ugh what a big dump that was

but the point is these are the two

mechanisms in which we think the

clozapine causes a granulocytosis super

interesting but why some people get it

and other people's don't we don't know

and what like it's only 99 plus percent

of people will never have this okay it's

it's less than one percent and who will

experience this and why is that we don't

know there are people right now in Labs

trying to work out if there's a genetic

element and there's some very hopeful

researchers out there so it might be a

genetic thing and if that if it is then

that's great because there'll be genetic

testing to predict who'll get it uh and

then maybe the monitoring can be less

stringent because we'll talk about that

at the end so this is the thing that uh

is the reason that people need to get so

many frequent blood tests while they

start clozapine but we won't go through

all the monitoring right now let's keep

going in the side effects the next side

effect to know about is myocarditis

which is essentially inflammation of the

heart muscles and I guess the key

takeaway about a key takeaway for

myocarditis if you're a healthcare

professional or not if you're someone

taking closer bed is to know that the

most common symptom is not chest pain

all right let that sit in and this is

why we do our blood tests to pick up

like we do troponins on the blood test

which is a cardiac enzyme which shows us

that if there's any myocarditis

happening

um it indicates if there could be

myocarditis happening just to clarify

but uh yeah uh Knight is common symptoms

is actually just feeling like crap it's

General malaise fever-like symptoms so

if you ever have a fever while you're

starting cause of pain or if you're on

cause pain you need to get an urgent

medical review uh because fevers can

mean it can mean a granulocytosis and an

immunocompromised State getting an

infection or it could mean myocarditis

you're feeling like crap you're feeling

lethargic you're feeling flu-like uh

it's it's really bad to get my God

either so uh so

um that's the that's the other thing we

also do monitoring with the ECG

uh to pick up on this because you can

see changes on the ECG now those are the

two rare side effects that people think

clozapine need to know about but

um let's also talk about the common side

effects that uh kind of really affect

compliance with clozapine and can can

ruin people's lives if they're not you

know on top of them so the first one

that people are usually a little bit

embarrassed about is hyper salivation so

it makes people drool especially at

night when they're going to sleep and

they wake up with pillows that are

drenched so a couple of things there are

ways to reduce this first you can get

specialized pillows they're called

clozapine pillows look them up on Google

or ask your clozapine Clinic if they

have any and they're either waterproofed

or they're like towel like absorbent and

the second thing is you can ask your

doctor for different strategies with

medications so there are atropine drops

or hyacin tablets so not tablets

lozenges that dry up your mouth and so

these help reduce hyper salivation it

doesn't fully eliminate it and the weird

thing is it's not dose dependent it's

not like reducing clozapine makes you

salivate less and it's hard it's

impossible to predict who's gonna get it

because not everyone has hyper

salivation some people are on 900

milligrams of Clozapine with a dry mouth

and others are on 150 milligrams of

Clozapine and it's just you know it's a

it's a bloody Fountain the reason this

happens it's probably a mix of reasons

there's a there's a cholinergic element

to the medicine and there's also a lack

of swallowing that occurs overnight when

you're sleeping so it's probably a mix

of both

all right the next common side effect to

sedation yes uh all antipsychotics can

sedate uh and this is no exception so

um you know the ways to address that is

that is dose responsive so you work with

your doctor to find the optimal dose for

you and the optimal time to take your

dose so if you're taking your dose at

midnight and you're waking up groggy

yeah no wonder like take it early take

it at seven and then usually it's a bit

better by the time you need to get up

it's worth noting though that coffee

doesn't fix this so people have I've met

people smashing 10 coffees in the

morning to try and beat

um the sedation from antipsychotics

caffeine ain't gonna fix the sedation

from antipsychotics guys you've got to

work with your doctors to to find the

right treatment for you and there's

probably a bit of acceptance that needs

like realistically unite except there

will be just some sedation with these

medicines but it's better than being

psychotic

anyway easy for me to say so uh the next

side effect to talk about is

um

the most this is the most common it's

weight gain all right weight gain people

can get fat on clozapine if you're not

really careful when you start on

clozapine you are starting on daily gym

and a healthy diet for the rest of your

life if you aren't ready for that you

need to really think you know you need

to be careful because clozapine will

make you eat more than you should and

and then you grow and you get diabetes

and all the rest of it so

um I hope that one message is clear is

that if you're going to start clozapine

you need to get into the mentality that

you're going to do lots of exercise and

eat like healthy foods you're going to

eat more than you want I don't know how

to prevent that but

but hopefully just choose healthier

foods people just crave greasy food when

they're on antipsychotics I don't know

why not like I've looked into the

research and it's just not really clear

why this happens but but you just gotta

you know you just gotta do lots of

exercise and eat as healthy as you

possibly can because it's it's so common

a really cool thing about clozapine

though is that there is not much epse or

movement side effects and in fact if

people have had tardive dyskinesia where

their mouth and booze involuntarily

because of other medicines that they

take cause of pain is a great

alternative because it actually reduces

tardive dyskinesia all right guys it's

time to talk about the monitoring and if

you've made it till now good on you

because this is the most important part

but also the hardest part to talk about

it's it's really a tough medicine to

start but once you've started it's much

more realistic so usually it started as

an inpatient and you start at very small

doses at like less than a tenth of what

you will end up on you start on so it's

12.5 milligrams then 25 then then 50

then and it builds up slowly

over the days in its neural tablet

obviously

so so it's important they come into an

inpatient so that they can do that slow

increase in medicines but also so that

they can do all the monitoring so in

terms of the monitoring before you start

the medicine you're going to get a full

set of Bloods including

um your your like cholesterol levels but

then all the other Bloods including your

red blood cells your lights your liver

function your kidney function your your

oh yeah uh like iron studies is a good

idea and hematinx like B12 folate uh

they're all good ideas to start off

before you start on clozapine

um I guess it's important to know that

there are different protocols in

different countries so and in different

states so in my state I use something

called the ecpms system which which is

the cause of real companies system and

cause real is a type of clozapine it's

the brand name for one of the clozapines

and

this is that this is the guidelines like

this is two pages per sheet and there's

like uh 30 pages so you know it's like

100 Pages uh and it tells you all the

monitoring that the doctors have to do

it's usually freely available if you if

you email the the um uh the company or

ask your doctor you can probably read it

I wouldn't have any problems with

someone reading this

and uh yeah so all the blood tests you

need to get an ECG where they look at

your heart electrical Pathways you need

to get a

um

echocardiogram where they look at your

heart with an ultrasound and I think

that's about it before starting but then

you need to get blood tests and you need

to get weekly blood tests and this this

is variable across the world

um but in in where we are It's weekly

blood tests for 16 weeks sorry

correction for 18 weeks here and then it

goes to monthly after 18 weeks because

after 18 weeks it's really unlikely that

you get the myocarditis or the

neutropenia which we talked about

earlier and listen this is where you

make the point around compliance this is

where I should talk about compliance

sorry uh if you stop cause of pain for

72 hours three days

you have to restart all of this so if

you've been taking clozapine for months

or years please don't just forget your

dose for three days in a row you know go

to the hospital if you need to they'll

help they'll give you a dose they'll

sort it out because if you miss three

days of clozapine again this depends on

where you are in the world in in

Australia you have to restart the whole

monitoring process again and yes some

people can do it in the community but

most of the time it means you have to go

into hospital to do it as an inpatient

so that they can do all the regular

thorough monitoring and after you finish

that really intense kind of um 18 weeks

of blood tests every week you can go to

monthly and you join What's called the

clozapine Clinic where you see a

clozapine nurse or doctor once a month

for the rest of your life so look you

know it is a intense regime but it is

such an effective medicine that it's

worth the kind of the price you pay in

terms of the monetary in fact people

think that going regularly to see the

nurse doctor keeps the engagement up

which actually keeps people well because

then the nurse or the doctor will pick

up if there's any kind of symptoms now

there are moves uh and right and then

people talking about making the

monitoring of clothes being less

stringent because of how good a medicine

it is and how rare the

um kind of neutrophil neutropenia is uh

it's kind of unfair to kind of require

such intense monitoring for people who

like there's a lot of people who aren't

on clozapine because they can't meet the

monitoring requirements and those people

are being done a disservice because

um because of essentially fear that they

might get neutropenia that's missed but

my view my personal opinion and remember

I'm a I'm a doctor in training I'm not a

psychiatrist and you need to talk to

your psychiatrist about their opinion

before you take any of these medicines

obviously

um but my opinion is it should the risk

should you know we should promote

people's autonomy in assessing risk it

should be up to the patient to accept or

not accept risk with the with monitoring

requirements so if they choose to do

every three months and they understand

that that comes at an increased risk of

getting

um uh you know neutropenia then then we

should you know that's that's an

important thing for the doctors to

appreciate that being said I've seen a

lot of neutropenia I've never seen

anyone die from it because we always

pick it up so early with these regular

blood tests so

um maybe my opinion would change if I

saw someone become really unwell with it

all right guys that is it for this video

um I hope that was uh useful

um my conclusion is that uh clozapine is

an extremely effective medicine for

people who have not responded to other

antipsychotics if I had schizophrenia I

would take clozapine that's what I would

want because of how effective it is and

how it changes people's lives the key

thing is just keep that compliance going

just take the bloody medicine I know

it's not perfect I know there are side

effects I know it sucks but it's better

than the alternative and if you want to

start just talk to your doctor first do

always talk to your bloody doctor first

guys that's my advice

um I wish you all an absolutely

beautiful day and I'll see you in the

next video alright bye for now