PSYCHOSIS + SCHIZOPHRENIA: CLOZAPINE

Question 1

Which antipsychotic is the most effective?

Answer 1

Clozapine

Question 2

Clozapine

Answer 2

2nd generation (atypical) antipsychotic
Most effect

Question 3

MOA

Answer 3

• Acts on D1 and D2 receptors
• 5-HT2a
• Alphal adrenoreceptors
• Muscarinic-receptor antagonist

Question 4

When would clozapine be initiated?

Answer 4

• Uncontrolled despite the
  sequential use of 2 or more drugs (one of which needs to be a non-clozapine second generation antipsychotic)
• They would have had to try each drug for at least 6-8 weeks before being considered
• Would be initated by a specialist

Question 5

Why is clozapine last line?

Answer 5

LOTS OF SIDE EFFECTS

Question 6

SEs

Answer 6

1. Metabolic syndrome
2. Myocarditis and cardiomyopathy
3. Neutropenia and agranulocytosis
4. Venous thromboembolism (VTE)
5. Sedation
6. Constipation
7. Hypersalivation

Question 7

Metabolic syndrome

Answer 7

• Weight gain, high lipid, diabetes

Question 8

Myocarditis and cardiomyopathy

Answer 8

• Signs include: Fever, fatigue, chest pain, palpitations, low BP, SOB (basically any heart failure signs)

Question 8

Neutropenia and agranulocytosis

Answer 8

Watch out for sore throat, flu-like symptoms

Question 9

Venous thromboembolism (VTE)

Answer 9

• Assess risk factors and use
  VTE prophylaxis accordingly

Question 10

Sedation

Answer 10

Common in early weeks, but tolerance to it develops

Question 11

Constipation

Answer 11

• DO NOT DELAY USING
  LAXATIVES
• MHRA/CSM warning risk of intestinal obstruction and
  faecal impaction
• Avoid use of drugs which may cause constipation e.g.
  Codeine

Question 12

Hypersalivation

Answer 12

Can use hyoscine hydrobromide (kwells) to treat it

Question 13

What are the monitoring requirements for Clozapine?

Answer 13

1. Leucocyte and differential blood counts
2. Blood lipids and weight
3. Fasting blood glucose
4. ECG

Question 14

Leucocyte and differential blood counts

Answer 14

• weekly for 18 weeks
• Every 2 weeks for up to a year
• monthly as part of clozapine patient monitoring service
• Discontinue if Leucocyte < 3000/mm3 or absolute neutrophil count < 1500/mm3

Question 15

Blood lipids and weight

Answer 15

• Baseline
• every 3 months for the first year
• then yearly

Question 16

Fasting blood glucose

Answer 16

• baseline
• One month
• every 4-6 months

Question 17

ECG

Answer 17

Before

Question 18

Who can dispense
Clozapine?

Answer 18

• Only pharmacies registered with an appropriate Patient
  Monitoring service
• The pharmacy, patient, and prescriber must be registered with the clozapine manufacturer and patient monitoring service

Question 19

What must you do before dispensing
Clozapine?

Answer 19

• Dose + brand
• Blood test
• When where they 1st initiated

Question 20

What if a patient misses a dose of Clozapine?

Answer 20

• If they miss more than 48 hours, then they would need to have their dose re-titrated
• Therefore referral back to the specialist is important!
• So DO NOT DISPENSE if they have missed more than 2 days

Question 21

What are the three brands of Clozapine?

Answer 21

• Clozaril
• Denzapine
• Zaponex

Question 22

Does Clozapine need to be brand specific?

Answer 22

YES!
- Each brand has its OWN mandatory monitoring system

Question 23

How is the dose of Clozapine initiated and titrated?

Answer 23

1. 12.5mg OD/BD
2. then 25-50mg on day 2
3. Then increase in steps of
   25-50mg daily up to MAX
   300mg daily (over 14-21 days)
4. After can increase in steps of 50-100mg a week up to
   MAX 900mg daily
   OVERALL VERY SLOWLY

Question 24

If it don’t work

Answer 24

Add a second antipsychotic to augment clozapine