Clozapine is an atypical antipsychotic that is used for treatment-resistant schizophrenia and other psychotic disorders. It works by antagonizing serotonin, dopamine, and other receptors with relatively low potency for the D2 receptor. This allows it to be effective without causing extrapyramidal side effects. Clozapine has indications for treatment-resistant schizophrenia, tardive dyskinesia, mania, and others. It requires monitoring of white blood cell counts due to the risk of agranulocytosis. Common side effects include sedation, dizziness, tachycardia, nausea, and weight gain.

1. Clozapine
Presenter: Abdul Waris Khan
5th Year M.B.B.S
Sulaiman Al-Rajhi Colleges
Welcome!

2. Obectives
SLIDE 2
Introduction to
clozapine
Indications
Treatment
protocol
1 2 3 4
Side effects

3. IntroductionSection 01

4. SLIDE 4
• Clozapine is an Atypical antipsychotic.
• First of the antipsychotics to be developed by Sandoz in
1961.
• Introduced in Europe in 1971 and withdrawn in 1975.why?
• FDA approved clozapine for only treatment-resistant
schizophrenia

5. SLIDE 5Mechanism of action
• Clozapine is an antagonist of 5-HT2A, Di, D3, D4, and
a (especially a1) receptors. It has relatively low potency
as a D2 receptor antagonist. Data from PET scanning
show that whereas 1 0 mg of haloperidol produces 80
percent occupancy of striatal D2 receptors, clinically
effective dosages of clozapine occupy only 40 to 50
percent of striatal D2 receptors.
• This difference in D2 receptor occupancy is
probably why clozapine does not cause EPS.

6. SLIDE 6

7. Indications
SLIDE 7
Treatment-resistant schizophrenia
Tardive dyskinesia
Patients suffering from EPS (due to other class of
medications)
Treatment resistant mania
Psychotic depression
Idiopthic parkinsons disease
Suicide patients with schizophrenia

8. Treatment protocol

9. SLIDE 8
• Before initiating treatment with clozapine, a complete blood count
(CBC) with differential should be performed and the patient’s
general and cardiovascular health status should be evaluated.
• Treatment should be initiated at a low dose (12.5– 25 mg once or
twice daily) and increased gradually (by no more than 25–50
mg/day) as tolerated until a target dose is reached.
• The clozapine package label states that WBC and neutrophil counts
should be evaluated before treatment is initiated, weekly during the
first 6 months of treatment and at least every 2 weeks after 6
months of treatment.
• Clozapine treatment should not be initiated if the initial WBC count
is <3500/mm3

10. SLIDE 9

11. Dozages
SLIDE 10
Clozapine is available in 25 mg and 100 mg tablets. The
initial dosage is usually 25 mg one or two times daily,
although a conservative initial dosage is 1 2.5 mg twice
daily. The dosage can then be increased gradually (25 mg
a day every 2 or 3 days) to 300 mg a day in divided doses,
usually two or three times a day. Dosages up to 900 mg a
day can be used. Testing for blood concentrations of
clozapine may be helpful in patients who fail to respond.
Studies have found that plasma concentrations greater
than 350 μg/mL are associated with a better likelihood of
response.

12. Side effects

13. Side effects
SLIDE 11
• The most common:
• sedation
• dizziness
• syncope
• tachycardia
• hypotension
• electrocardiography (ECG) changes
• nausea, and vomiting
• Fatigue
• weight gain
• subjective muscle weakness
• sialorrhea
• Seizures
• Leukopenia
• Agranulocytosis (0.73% risk)
• Neutropenia

14. Weight gain and Metabolic syndrome
SLIDE 12

15. References
SLIDE 13
American psychiatric association
guidelines.
Kaplan and sedock’s synopsis of
psychiatry.

16. That’s all. Thank you very much! 
Any Questions?