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Antipsychotics: The Essentials
Module 5: A Primer on Selected Antipsychotics
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
1
Slide 1
This is the last module, it´s a primer
on selected antipsychotics.
Slide 2
Before beginning with the discussion
of each drug, let me give you a
preview of how I’ve organized this
module.
I have selected 13 antipsychotics, 3
are first generation agents and 10 are
second generation agents. As you
may see, there is an emphasis on
second generation antipsychotics.
This is because prescribers are often
interested in knowing more about the new drugs they hear about.
Please keep in mind that first generation antipsychotics are still extremely valuable drugs,
especially for situations in which costs of new drugs may be prohibitive.
If you are interested in learning up-to-date detailed information about first generation
antipsychotics, I would recommend you to check a recent review published in Advances in
Psychiatric Treatment by Dr. Owens. You can look for the title it in the references slide.
The structure for each antipsychotic is the following:
- First we’ll study the most relevant features regarding binding profiles. These are just highlights
that often have clinical implications, we won’t go into exhaustive pharmacodynamic detail.
Antipsychotics: The EssentialsModule 5
A Primer on Selected Antipsychotics
Flavio Guzmán, MD
Antipsychotics: The EssentialsModule 5
A Primer on Selected Antipsychotics
Flavio Guzmán, MD
About this module
• 13 antipsychotics will be studied– 3 first generation antipsychotics
– 10 second generation antipsychotics
• Plan:– Binding profile (highlights, not exhaustive)
– Basic prescribing information
– Main clinical features of each AP
About this module
• 13 antipsychotics will be studied– 3 first generation antipsychotics
– 10 second generation antipsychotics
• Plan:– Binding profile (highlights, not exhaustive)
– Basic prescribing information
– Main clinical features of each AP
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
2
Second, I’ll describe basic prescribing information, mainly dosage range and dosage forms.
Third, I’ll present main clinical features of each drug.
Slide 3
One last clarification: all
antipsychotics mentioned in this
presentation are approved for the
treatment of schizophrenia.
This means that when we reach the
clinical features part and discuss
approved indications I’ll be
mentioning additional uses besides
schizophrenia.
Slide 4
The list of antipsychotics we’ll study is
the following:
Chlorpromazine (Thorazine)
Haloperidol (Haldol)
Perphenazine ( Trilafon)
Clozapine (Clozaril)
Olanzapine (Zyprexa)
Risperidone (Risperdal)
Paliperidone (INVEGA)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Aripiprazole (Abilify)
Iloperidone (Fanapt)
Asenapine (Saphris)
Lurasidone (Latuda)
About this module
• All antipsychotics mentioned in this presentation are approved for the treatment of schizophrenia.
About this module
• All antipsychotics mentioned in this presentation are approved for the treatment of schizophrenia.
Antipsychotics
• Chlorpromazine (Thorazine)• Haloperidol (Haldol)• Perphenazine ( Trilafon)• Clozapine (Clozaril)• Olanzapine (Zyprexa)• Risperidone (Risperdal)• Paliperidone (INVEGA)• Quetiapine (Seroquel)
• Ziprasidone (Geodon)• Aripiprazole (Abilify)• Iloperidone (Fanapt)• Asenapine (Saphris)• Lurasidone (Latuda)
Antipsychotics
• Chlorpromazine (Thorazine)• Haloperidol (Haldol)• Perphenazine ( Trilafon)• Clozapine (Clozaril)• Olanzapine (Zyprexa)• Risperidone (Risperdal)• Paliperidone (INVEGA)• Quetiapine (Seroquel)
• Ziprasidone (Geodon)• Aripiprazole (Abilify)• Iloperidone (Fanapt)• Asenapine (Saphris)• Lurasidone (Latuda)
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
3
Slide 5
Let´s begin with one of the oldest
antipsychotics, chlorpromazine. This
is a low potency first generation
antipsychotic, as you remember, this
means that high doses are required
for achieving therapeutic effect.
One of the reasons why
chlorpromazine is still relevant is that
it is used as comparator for
antipsychotic dose equivalence.
Slide 6
Let’s study its binding profile.
Chlorpromazine has antagonist action
at D2 receptors, this is linked to its
efficacy as an antipsychotic.
Regarding other receptors,
chlorpromazine is an antagonist at
histamine 1 receptors, alpha 1 and
muscarinic receptors.
Histamine 1 antagonism is linked to one the effects most typically associated with
chlorpromazine use: sedation.
Alpha 1 antagonism increases the risk of orthostatic hypotension, it’s important to keep in mind
this side effect especially in an acute setting.
Chlorpromazine also blocks 5HT2A receptors, but not as potently as second generation drugs.
Chlorpromazine
• One of the first antipsychotics
• Low potency FGA (high doses required for therapeutic effect)
• Used as comparator for antipsychotic dose equivalence
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Chlorpromazine
• One of the first antipsychotics
• Low potency FGA (high doses required for therapeutic effect)
• Used as comparator for antipsychotic dose equivalence
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Chlorpromazine: binding profile
- D2 antagonist- H1 antagonist- Alpha 1 antagonist- Muscarinic antagonist- 5HT2A antagonist
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Chlorpromazine: binding profile
- D2 antagonist- H1 antagonist- Alpha 1 antagonist- Muscarinic antagonist- 5HT2A antagonist
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
4
Slide 7
Chlorpromazine dosage ranges from
200 to 800 mg/day. Current
suggested dosing is between 400 and
600 mg/day.
Regarding dosage forms,
chlorpromazine is available as tablets
of 10, 25, 50, 100 and 200 mg.
As capsules of 30, 75, 150 mg
As ampul of 25 mg/ml, 1 ml and 2 ml.
As liquid drug 10 mg / 5ml.
And as suppository of 25 and 100 mg.
Slide 8
From a clinical perspective,
chlorpromazine as advantages and
disadvantages.
Among the advantages we can list:
Long established use.
High margin of safety.
Its sedative properties, this is an
advantage for acute patients.
The disadvantages include:
Tolerability is less favorable than safety.
Generally it’s too sedative for long term use.
Chlorpromazine: prescribing facts• Dosage range:
– 200-800 mg/day– Current suggested dosing: 400-600mg/day
• Dosage forms– Tablets: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg– Capsules: 30 mg, 75 mg, 150 mg– Ampul: 25 mg/ml, 1ml, 2ml– Liquid: 10 mg/ 5 ml– Suppository 25 mg, 100 mg
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Chlorpromazine: prescribing facts• Dosage range:
– 200-800 mg/day– Current suggested dosing: 400-600mg/day
• Dosage forms– Tablets: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg– Capsules: 30 mg, 75 mg, 150 mg– Ampul: 25 mg/ml, 1ml, 2ml– Liquid: 10 mg/ 5 ml– Suppository 25 mg, 100 mg
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Chlorpromazine: Clinical Profile
Advantages
• Long established use
• High margin of safety
• Sedative
Disadvantages
• Tolerability less favorable than safety
• Generally too sedative for long term use
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Chlorpromazine: Clinical Profile
Advantages
• Long established use
• High margin of safety
• Sedative
Disadvantages
• Tolerability less favorable than safety
• Generally too sedative for long term use
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
5
Slide 9
The next drug in our list is
haloperidol. This is a high potency
first generation antipsychotic that has
high risk of causing EPS, it is available
as long acting injection, which is an
advantage in terms of treatment
adherence for some patients
Slide 10
Haloperidol has a relatively simple
binding profile. It has very high
affinity for D2 receptors, this strong
D2 blocking property has a correlation
in terms of extrapyramidal symptoms.
It also has affinity for sigma receptors.
Haloperidol doesn’t have significant
affinity for histamine 1 or muscarinic
receptors, this makes it a drug with
low potential to cause sedation or anticholinergic effects.
Haloperidol
• High potency FGA
• High risk of causing EPS
• Available as LAI
Haloperidol
• High potency FGA
• High risk of causing EPS
• Available as LAI
Haloperidol: Binding Profile
- Very high affinity for D2 receptors
- Affinity for s receptors- No significant action for H1
and M receptors
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Haloperidol: Binding Profile
- Very high affinity for D2 receptors
- Affinity for s receptors- No significant action for H1
and M receptors
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
6
Slide 11
Haloperidol has a wide dosage range,
from 1 to 40 mg/ day orally.
Brain imaging studies show that low
doses of haloperidol, less than 5
mg/day can occupy 80% of D2
receptors, this percentage of
occupancy is associated with clinical
efficacy.
Slide 12
Available dosage forms include:
Scored tablets: 0,5 mg, 1 mg, 2 mg, 5
mg, 10 mg, 20 mg.
Concentrate: 2 mg/ml
Solution: 1 mg/ml
Injection 5 mg/ml
LAI - Decanoate formulation:
50 mg haloperidol as 70.5 mg/ml
haloperidol decanoate.
100 mg haloperidol 141.04 mg/ml haloperidol decanoate
Haloperidol- Prescribing Facts
• Dose range:
– 1-40 mg/day orally
– Efficacy can be obtained with low doses (less than 5 mg/day).
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Haloperidol- Prescribing Facts
• Dose range:
– 1-40 mg/day orally
– Efficacy can be obtained with low doses (less than 5 mg/day).
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Haloperidol- Prescribing Facts
• Dosage forms:– Scored tablets: 0,5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg.
– Concentrate: 2 mg/ml
– Solution: 1 mg/ml
– Injection 5 mg/ml
– LAI - Decanoate formulation: • 50 mg haloperidol as 70.5 mg/ml haloperidol decanoate.
• 100 mg haloperidol as 141.04 mg/ml haloperidol decanoate.
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Haloperidol- Prescribing Facts
• Dosage forms:– Scored tablets: 0,5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg.
– Concentrate: 2 mg/ml
– Solution: 1 mg/ml
– Injection 5 mg/ml
– LAI - Decanoate formulation: • 50 mg haloperidol as 70.5 mg/ml haloperidol decanoate.
• 100 mg haloperidol as 141.04 mg/ml haloperidol decanoate.
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
7
Slide 13
In clinical terms, the advantages of
haloperidol include:
- Long established use. Haloperidol
was approved in 1967, since then it
has been extensively used.
- It’s very useful in psychiatric
emergencies. The lack of alpha 1
antagonism makes it a drug with low
risk of causing orthostatic hypotension, which is an benefit for parenteral use.
The disadvantages:
- Because of its strong affinity for D2 receptors, it has very high liability to produce
extrapyramidal symptoms.
- The perception of dosage is higher of what pharmacology suggests.
Slide 14
Perphenazine is an intermediate
potency first generation drug that
served as active comparator in the
CATIE trial.
Haloperidol: Clinical Profile
Advantages
• Long established use
• Very useful in psychiatric emergencies
Disadvantages
• Very high liability to produce EPS
• Perception of dosage higher of what pharmacology suggests
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Haloperidol: Clinical Profile
Advantages
• Long established use
• Very useful in psychiatric emergencies
Disadvantages
• Very high liability to produce EPS
• Perception of dosage higher of what pharmacology suggests
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Perphenazine
• Intermediate potency FGA
• Served as active comparator in the CATIE trial
Perphenazine
• Intermediate potency FGA
• Served as active comparator in the CATIE trial
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
8
Slide 15
Perphenazine has an intermediate
affinity for D2 receptors, compared to
haloperidol it’s a weaker D2
antagonist. It has significant alpha1
antagonist action and it’s also a
histamine 1 antagonist.
This pharmacological profile should
remind us of risk of orthostatic
hypotension and sedation.
Slide 16
The dosing range of Perphenazine
goes from 12 to 24 mg/day. Here we
can see two situations worth noting,
the CATIE trial allowed up to 32 mg/
day. Also in hospitalized patients, the
daily dose can range from 16 to 64
mg.
The dosage forms are tablets and an
injection.
There are available tablets of 2, 4, 8 and 16 mg.
The injection is a formulation of 5 mg/ml.
Perphenazine: Binding Profile
- Intermediate affinity for D2 receptors
- Significant a 1 antagonist action
- H1 antagonist
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Perphenazine: Binding Profile
- Intermediate affinity for D2 receptors
- Significant a 1 antagonist action
- H1 antagonist
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Perphenazine: Prescribing Facts
• Dosage range:– 12-24 mg/day
• CATIE allowed up to 32 mg/day
• 16-64 mg/day in hospitalized patients
• Dosage forms– Tablets: 2 mg, 4 mg, 8 mg, 16 mg
– Injection: 5 mg/ml
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Perphenazine: Prescribing Facts
• Dosage range:– 12-24 mg/day
• CATIE allowed up to 32 mg/day
• 16-64 mg/day in hospitalized patients
• Dosage forms– Tablets: 2 mg, 4 mg, 8 mg, 16 mg
– Injection: 5 mg/ml
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
9
Slide 17
From a clinical perspective, the
advantages of Perphenazine include:
Long established use
High margin of safety (remember its
wide dosage range)
The fact that we got to know it
better through its use as active
comparator in the CATIE trial.
We also need to consider its disadvantages:
- It has a short half-life: between 8 to 12 hours, ideally is best administered three times daily.
This can be problematic in terms of treatment adherence.
Its potency and tolerability make easy for extrapyramidal symptoms to emerge undetected.
Slide 18
We’ll move now to the second
generation drugs. Clozapine was the
first of the second generation
antipsychotics to be approved, it has
unique therapeutic benefits and a
unique side effects profile.
Perphenazine: Clinical Profile
Advantages
• Long established use
• High margin of safety
• Better known through its use as active comparator in CATIE
Disadvantages
• Short half-life ( 8-12 hours): ideally is best administered three times daily.
• Potency and tolerability make easy for EPS to emerge undetected.
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Perphenazine: Clinical Profile
Advantages
• Long established use
• High margin of safety
• Better known through its use as active comparator in CATIE
Disadvantages
• Short half-life ( 8-12 hours): ideally is best administered three times daily.
• Potency and tolerability make easy for EPS to emerge undetected.
Owens D. Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1). Advances in Psychiatric Treatment 2012
Clozapine
• First of the SGAs
• Unique therapeutic benefits
• Unique side effects profile
Clozapine
• First of the SGAs
• Unique therapeutic benefits
• Unique side effects profile
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
10
Slide 19
This drug has a very complex
pharmacology. Because of the
reasons I mentioned earlier the
binding profile of clozapine has been
intensively studied.
I’ll refer to some of the most relevant
features, those that have implications
because of hypothetical mechanisms
of action or adverse effects.
Clozapine has a high 5HT2A/D2 ratio, this means despite being an antagonist for both receptors,
it has higher affinity for 5HT2A receptors.
The drug is also an antagonist at histamine 1, muscarinic and alpha 1 receptors. This is relevant
for potential side effects.
Antagonism at 5HT2C receptors has been associated to an increase in the risk of weight gain.
Slide 20
In addition, clozapine is an antagonist
at D3 and D4 receptors. Also, the drug
is a partial agonist at 5HT1A
receptors.
Clozapine: Binding Profile- High 5HT2A/D2 ratio- H1 antagonism- Muscarinic antagonism a 1 antagonism- 5HT2C antagonism
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Clozapine: Binding Profile- High 5HT2A/D2 ratio- H1 antagonism- Muscarinic antagonism a 1 antagonism- 5HT2C antagonism
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Clozapine: Binding Profile
- D3 and D4 antagonist- 5HT1A partial agonist
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Clozapine: Binding Profile
- D3 and D4 antagonist- 5HT1A partial agonist
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
11
Slide 21
The dosage range of clozapine goes
from 300 to 450 mg/day. In some
cases doses as high as 500 mg/day
can be used, we must remember that
seizure risk is dose dependent,
Dosage forms include tablets and
orally disintegrating tablets. Tablets
are available in presentations of 12.5
mg, 25 mg scored tablets, 50 mg, and
100 mg scored tablets.
Orally disintegrating tablets are available in formulations of 12.5, 25, 50 and 100 mg.
A pharmacokinetic fact worth noting is that clozapine is metabolized primarily by CYP1A2, with
additional contributions by CYP2C19, CYP2D6 and CYP3A4.
Slide 22
It’s important to take a moment to
identify the three clinical features
that make clozapine unique.
- The first is that clozapine is the only
antipsychotic that has proven
effective for treatment-resistant
schizophrenia. For a definition of
treatment-resistant schizophrenia I
would recommend you to check the
paper by Conley cited at the bottom of the slide.
The second concept is that clozapine reduces violence and persistent aggression in
schizophrenia.
Last, but definitely not least, long- term treatment is associated with reduction of risk of suicidal
behaviors.
Clozapine: Prescribing Facts• Dosage range:
– 300-450 mg/day– In some cases: higher than 500 mg/day (risk of seizures)
• Dosage forms:– Tablets: 12.5 mg, 25 mg (scored), 50 mg, 100 mg (scored)– Orally disintegrating tablets: 12.5 mg, 25 mg, 50 mg, 100
mg
• Metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Clozapine: Prescribing Facts• Dosage range:
– 300-450 mg/day– In some cases: higher than 500 mg/day (risk of seizures)
• Dosage forms:– Tablets: 12.5 mg, 25 mg (scored), 50 mg, 100 mg (scored)– Orally disintegrating tablets: 12.5 mg, 25 mg, 50 mg, 100
mg
• Metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Clozapine: Clinical Profile• Effective for treatment-resistant
schizophrenia.
• Reduces violence and persistent aggression in schizophrenia.
• Long-term treatment associated with reduction of risk of suicidal behaviors.
Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997
Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophrenia research 2005
Clozapine: Clinical Profile• Effective for treatment-resistant
schizophrenia.
• Reduces violence and persistent aggression in schizophrenia.
• Long-term treatment associated with reduction of risk of suicidal behaviors.
Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997
Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophrenia research 2005
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
12
Slide 23
Clozapine has a special adverse
effects profile.
- It’s one of the antipsychotics with
the lowest risk of causing EPS.
On the other hand, it’s one of the
antipsychotics with the highest
metabolic risk, the other is
olanzapine.
As we saw in the module on adverse effects, the risk of agranulocytosis requires periodic blood
monitoring.
It has a dose-dependent seizure risk.
Because of its antagonist effect at histamine 1 receptors it can be very sedating.
Slide 24
Olanzapine is a second generation
antipsychotic known to be less “dirty”
in pharmacodynamic terms than
clozapine.
It is available in combination with the
antidepressant fluoxetine as
olanzapine fluoxetine combination or
OFC.
Dosage forms include parenteral formulations.
Clozapine – Adverse Effects Profile
• One of the antipsychotics with the lowest EPS risk
• One of the antipsychotics with the highest metabolic risk
• Risk of agranulocytosis
• Dose-dependent seizure risk
• Can be very sedating
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Clozapine – Adverse Effects Profile
• One of the antipsychotics with the lowest EPS risk
• One of the antipsychotics with the highest metabolic risk
• Risk of agranulocytosis
• Dose-dependent seizure risk
• Can be very sedating
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Olanzapine
• SGA less “dirty” than clozapine.
• Available in combination with fluoxetine: OFC
• Dosage forms include parenteral formulations
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Olanzapine
• SGA less “dirty” than clozapine.
• Available in combination with fluoxetine: OFC
• Dosage forms include parenteral formulations
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
13
Slide 25
Olanzapine has a binding profile
similar to clozapine, but it interacts
with less receptors.
It has a high 5HT2A/D2 ratio, like
clozapine it is an antagonist at
histamine 1, muscarinic, alpha 1 and
5HT2C receptors. Antagonist actions
at 5HT2C and histamine 1 receptors
are thought to be related to an
increased risk of weight gain.
Because of its affinity for alpha 1 receptors, olanzapine can cause in some cases orthostatic
hypotension. Since this drug is available as IM injection, we need to remember this side effect
to avoid combining it with benzodiazepines.
Slide 26
The dosage range of olanzapine goes
from 10 to 20 mg / day. There are
several dosage forms that include oral
and parenteral formulations.
Tablets are available in doses of 2.5,
5, 7.5, 10, 15 and 20 mg.
Orally disintegrating tablets: 5, 10, 15
and 20 mg
Oral fluoxetine combination of 6 mg of fluoxetine and 25 mg of olanzapine, 6 and 50 mg, 12 and
25 and 12 and 50 mg.
An IM formulation for use in acute settings: 5 mg per ml, each vial contains 10 mg. This
formulation is available in some countries.
A long acting injection of olanzapine pamoate: doses of 150, 300, 210, 405 mg
Olanzapine – Binding Profile- High 5HT2A/D2 ratio- H1 antagonist- Muscarinic antagonist a 1 antagonist- 5HT2C antagonist
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Olanzapine – Binding Profile- High 5HT2A/D2 ratio- H1 antagonist- Muscarinic antagonist a 1 antagonist- 5HT2C antagonist
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008 Schatzberg, AF, Nemeroff, CB. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009
Olanzapine- Prescribing Facts• Dosage range:
– 10 – 20 mg/day
• Dosage forms:– Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg– Orally disintegrating tablets: 5 mg, 10 mg, 15 mg, 20 mg– OFC capsule: 6 mg/ 25 mg, 6 mg /50 mg, 12 mg/25 mg, 12
mg/50 mg– IM formulation: 5 mg/ml, each vial contains 10 mg (available in
some countries)– LAI: olanzapine pamoate: 150 mg, 300 mg, 210 mg, 405 mg
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Olanzapine- Prescribing Facts• Dosage range:
– 10 – 20 mg/day
• Dosage forms:– Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg– Orally disintegrating tablets: 5 mg, 10 mg, 15 mg, 20 mg– OFC capsule: 6 mg/ 25 mg, 6 mg /50 mg, 12 mg/25 mg, 12
mg/50 mg– IM formulation: 5 mg/ml, each vial contains 10 mg (available in
some countries)– LAI: olanzapine pamoate: 150 mg, 300 mg, 210 mg, 405 mg
Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
Antipsychotics: The Essentials Module 5. A Primer on Selected Antipsychotics
14
Slide 27
I’ve selected some interesting facts
about the clinical profile of
olanzapine:
Olanzapine/fluoxetine combination
was the first drug approved for
bipolar depression.
Olanzapine is associated with less EPS
than FGAs.
Weight gain is problematic with long term use. Olanzapine and clozapine are associated with
the highest risk of weight gain.
It can be a very sedating antipsychotic.
Olanzapine – Clinical Profile
• Olanzapine/fluoxetine combination was the first drug approved for bipolar depression.
• Associated with less EPS than FGAs.
• Weight gain is problematic with long term use.
• Can be very sedating.
Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.
Olanzapine – Clinical Profile
• Olanzapine/fluoxetine combination was the first drug approved for bipolar depression.
• Associated with less EPS than FGAs.
• Weight gain is problematic with long term use.
• Can be very sedating.
Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.