medications
Clozapine
Introduction
Clozapine (Clozaril) was the first atypical (or second generation) antipsychotic developed. It is only available by prescription and only from pharmacies who agree to participate in the required monitoring programs.
History
Clozapine was developed by Sandoz in 1961, but was not introduced to the market until 1971 when it became available in Europe. It was voluntarily withdrawn from the market in 1975 after some patients taking this drug developed agranulocytosis. In some instances this was fatal.
When research revealed that clozapine was more effective than other available agents in treating resistant Schizophrenia it was reintroduced with weekly lab testing1 to monitor WBC (white blood cell count).
Indications
Clozapine was approved by the FDA (Food and Drug Administration) in 1989 for the treatment of Schizophrenia. It is the only FDA approved medication for treatment-resistant Schizophrenia and for reducing the risk of suicide in patients who suffer from Schizophrenia and Schizoaffective Disorder.
Mechanism of Action
The exact mechanism of action for antipsychotic medications is not known. It is believed that its therapeutic effects are related dopamine receptor blockage.
Clozapine appears to be effective in treating both positive and negative symptoms, including cognitive impairment.
Potency
Clozapine is a low-potency antipsychotic agent.
Preparations
Clozapine is available in 25 and 100 mg tablets.
Side Effects
The most serious side effect is agranulocytosis, occurring in approximately 1% of patients who take this medication in the first six months of therapy and 0.01% thereafter.
It may cause myocarditis. Clozapine does not appear to cause the cognitive dysfunction seen with other psychoactive drugs.
Common side effects include:
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constipation -
drooling
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muscle stiffness
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sedation
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tremors
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orthostatic hypotension (falling blood pressure with sitting or standing)
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hyperglycemia
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weight gain.
Both EPSE and TD are less common in patients treated with this drug compared to those taking typical antipsychotics.
Clozapine may be more likely to produce Metabolic Syndrome X than other atypical antipsychotics.
Contraindications
This drug should not be used in patients with uncontrolled epilepsy, myeloproliferative diseases (those that interfere with the production of blood cells by the bone marrow), a history of agranulocytosis when exposed to this drug in the past or patients with known hypersensitivity (previous allergic reactions) to the medication or any of its components.
It should be used with caution in patients with known heart disease, impaired liver function or a history of seizures.
Clozapine is excreted in human breast milk. It has not been studied in pregnant women and children. Female patients who become pregnant, are considering pregnancy, who are not using contraception, or those who recently gave birth and are considering breast feeding should notify their physician immediately.
Disclaimer
Complete prescribing information can be obtained from your doctor or pharmacist, or by reviewing the package insert. Patients should take this medication only with the approval and supervision and their attending physician.
1Weekly WBC (white blood cell count) monitoring is required for the first six months and every other week for another six months and monthly thereafter.
(Sources: The FDA (Food and Drug Administration), PDR (Physician’s Desk Reference), Sandoz and Novartis, and the author’s knowledge base.)
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