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Clozapine Side Effects Atypical Antipsychotics Schizophrenia Psychosis Clozaril

Clozaril is an atypical antipsychotic drug prescribed to treat resistant schizophrenia. It was once withdrawn from the market due to serious side effects. But it was reintroduced, because of its effectiveness in treating resistant schizophrenia. However It can cause fatal agranulocytosis (disease characterized by lack of white cell type called granulocytes in the blood), which can be lethal. Its generic name is Clozapine.

Important!

Patients who are taking clozaril must be registered with a central monitoring agency. Patients should have their white blood cell count checked once a weekly for about eighteen weeks, then every two weekly for next six months. After that every four weekly till the discontinuation of the drug.

Is it effective?

Several evidence based clinical trials have confirmed Clozapine (clozaril) is more effective than other antipsychotic drugs for treatment of schizophrenia. In addition, NICE (National Institute of Clinical Excellence) guidelines recommends that “clozaril should be used in treatment resistant schizophrenia, where there has been a lack of satisfactory clinical improvement, with sequential use of two antipsychotics (one should be another atypical) in recommended doses for at least six to eight weeks.”

How it works?

Clozaril blocks both serotonin and dopamine receptors in certain brain areas. In contrast, conventional antipsychotics (Haloperidol, Largactil) act by blocking only the dopamine receptors. Dopamine blockade in some brain areas causes many side effects like acute dystonia, and drug induced Parkinsonism. Blocking serotonin increases dopamine levels in those areas (side effects causing areas). This interaction with serotonin and dopamine alleviate the side effects of dopamine blockade.

In addition, clozaril improves negative symptoms of schizophrenia such as social withdrawal (due to complex interaction between serotonin and dopamine). Reason for its superior efficacy is not fully understood by the scientists.

What the doctor will do, before writing the prescription?

The doctor will take a full history about patient’s illnesses and he/she will do a thorough physical examination before starting clozaril. In addition the doctor will do several blood tests and electrocardiogram before starting the treatment. In addition, clozaril is contraindicated in severe heart diseases, severe renal impairment, bone marrow disorders, uncontrolled epilepsy, and breast feeding. So the doctor will look into them.

What are the Side effects?

Main side effects are constipation, fever, increased salivation, hypertension or hypotension, nausea, sedation, seizures, myocarditis and weight gain. Most dangerous one is agranulocytosis.

How is it given?

Doctors usually start the drug in very small dose, and then gradually increase. As with any anti-psychotic drug it takes around two weeks to show signs of improvement. However side effects usually come before that.

Interactions

Clozaril should not be used with other drugs that are known to cause reduced white cell counts. It should not be used with drugs that cause seizures (fits). Plasma concentration of clozaril decreases with caffeine intake, smoking, drugs like carbamezapine, and dilantin sodium.

Summary

Clozaril is an atypical antipsychotic medication. It is only prescribed in resistant schizophrenia. Main problem associated with Clozaril is Agranulocytosis or reduction in white cells in blood.

Sources

Oxford handbook of psychiatry

British National Formulary 58th edition

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