Clozapine

Clozapine REF: Kaplan and sadock’s synopsis in psychiatry 10th ed p. 489-490

Antipsychotics can be categorized into two main groups: the older conventional antipsychotics, which have also been called first-generation antipsychotics or dopamine receptor antagonists (DRA), and the newer drugs, which have been called second-generation antipsychotics or serotonin dopamine antagonists (SDAs)

Strategies for Poor Responders of Antipsychotic:

• It may suggest that the patient is a rapid metabolizer of the antipsychotic or that the drug is not being adequately absorbed.
• Changing to another drug is preferable to changing to a high dose.
• If a patient has responded poorly to a conventional DRA, it is unlikely that this individual will do well on another DRA. Changing to an SDA is more likely to be helpful.
• Clozapine is effective for patients who respond poorly to DRAs. Double-blind studies comparing clozapine to other antipsychotics indicated that clozapine had the clearest advantage over conventional drugs in patients with the most severe psychotic symptoms, as well as in those who had previously responded poorly to other antipsychotics.

Clozapine has been approved for,

• Patients with schizophrenia who have failed to respond adequately to typical neuroleptic drugs (treatment-resistant schizophrenia)
• Patients who are intolerant of typical neuroleptic drugs because of EPS or tardive dyskinesia
• Patients who are at high risk for suicide

Valproic acid is an anticonvulsant used as a mood stabilizer. It is found useful in the treatment of mania in a bipolar disorder.

It has also been valuable in the treatment of rapid cycling bipolar patients.

Paroxetine is an example of a selective serotonin reuptake inhibitor (SSRI), which is a newer form of antidepressant.

The SSRis are being found to be as effective as the tricyclic antidepressants.

Haloperidol is an example of a neuroleptic or antipsychotic medication useful in the management of acute psychosis, as well as long-term care. Clozapine is a newer atypical antipsychotic medication.

It is not associated with tardive dyskinesia as are the older neuroleptics.

This makes it a drug of choice for individuals who have developed signs of tardive dyskinesia after using other neuroleptics.

Problems with agranulocytosis prevent clozapine from being used as a “first line” neuroleptic.  

Ref: Meltzer H.Y., Bobo W.V., Heckers S.H., Fatemi H.S. (2008). Chapter 16. Schizophrenia. In M.H. Ebert, P.T. Loosen, B. Nurcombe, J.F. Leckman (Eds),CURRENT Diagnosis & Treatment: Psychiatry, 2e. 

C i.e. Clozapine 

D i.e. Extrapyramidal side effects are seen

B i.e. Blood level should be maintained

B i.e. Clozapine

Ans:B-Clozapine

• Clozapine is an antipsychotic drug with least extrapyramidal side effects, i.e. it has least chances of producing muscular dystonia, akathisia, malignant neuroleptic syndrome, & tardive dyskinesia.
• The patient who has depression & auditory hallucinations & is being treated with CPZ i.e. the patient is a case of schizophrenia.
• The patient is a case of resistant schizophrenia as the auditory hallucinations are not responding to treatment.
• As you must know – Auditory hallucinations are first symptom to go with treatment & also 1^st symptom to reappear after drug resistance.

A i.e. Clozapine

B i.e. Sialorrhea

Ans:B-Clozapine

Common side effects of clozapine include:

1. Sedation
2. Hypersalivation
3. Tachycardia
4. Hypotension
5. Hypertension
6. Weight gain
7. Constipation 
8. Hepatic effects
9. Urinary incontinence
10. Fever

Serious side effects include:

1. Agranulocytosis
2. Cardiovascular/respiratory arrest
3. Seizures

A i.e. Trifluperazine; B i.e. Clozapine; C i.e. Haloperidol

Ans. is ‘d’ i.e., Extrapyramidal side effects

Side effects of clozapine

o Agranulocytosis             o Unstable BP & Tachycardia                 o Worsening of diabetes                     o Seisures

o Urinary incontinence      o Hypersalivation (sialorrhoea)              o Weight gain                                   o Sedation

Ans. is ‘a’ i.e., Clozapine

o Antipsychotics with no extrapyramidal effects.

1. Clozapine                  2. Aripiprazole                      3. Quetiapine

o Amongst typical antipsychotics, thioridazone has least extrapyramidal effects.

Ans. is ‘d’ i.e., Weight loss

Clozapine causes weight gain.

Ans. is ‘c’ i.e., Clozapine

o Drugs for negative symptoms

• Clozapine 
• Olanzapine 
• Risperidone 
• Aripiprazole 
• Ziprazidone

Ans. is ‘d’ i.e., Clozapine

o Clozapine (but not the newer atypicals) is more effective than classical agents for resistant schizophrenia.

Ans. is ‘a’ i.e. Clozapine

Potential of antipsychotic drugs to cause metabolic syndrome

• High Potential: Clozapine, Olanzapine, Chlorpromazine, thioridazine
• Intermediate potential: Quetiapine
• Low potential: Risperidone, Paliperidone
• Least potential: Iloperidone, aripiprazole, asenapine, ziprasidone.

Ans: A i.e. Clozapine

Ans. C: Clozapine

Clozapine

• It may inhibit serotonin, muscarinic, and dopamine effects.
• Revolutionized treatment of medication-resistant schizophrenia.
• Effective in 30% of patients in whom other medications have failed.
• May improve tardive dyskinesia resulting from long-term use of traditional antipsychotics.
• Major drawback of reversible agranulocytosis occurs in 1-2%
• Interactions-Epinephrine and phenytoin may decrease effects; tricyclic antidepressants, neuroleptics, CNS depressants, guanabenz, and anticholinergics may increase effects
• Contraindications-Documented hypersensitivity; WBC (less than 3500 cells per millimeter cube) before or during therapy.
• Precautions-Pregnancy, Do not abruptly stop the medication; to minimize risk of agranulocytosis.

Ans. is ‘b’ i.e., Clozapine

Agranulocytosis is a known side effect of clozapine

“Because of the risk of agranulocytosis, patients, recieving clozapine must have weekly blood counts for the first 6 months and every 3 weeks thereafter”

Side effects of clozapine

• Agranulocytosis
• Unstable BP & Tachycardia 
• Worsening of diabetes
• Seisures
• Urinary incontinence
• Hypersalivation (sialorrhoea) 
• Weight gain
• Sedation