Clozapine chemical structure
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Clozaril

Clozapine (sold as Clozaril®, Leponex®, Fazaclo®) was the first of the atypical antipsychotics to be developed. It was approved by the United States FDA in 1989 and is the only FDA-approved medication indicated for treatment-resistant schizophrenia and for reducing the risk of suicidal behaviour in patients with schizophrenia. more...

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History and main uses

Clozapine was developed by Sandoz in 1961, and introduced in Europe ten years later. In 1975, after reports of agranulocytosis leading to death in some clozapine-treated patients, Clozapine was voluntarily withdrawn by the manufacturer. Clozapine fell out of favor for more than a decade. However, when studies demonstrated that clozapine was more effective against treatment-resistant schizophrenia than other antipsychotics, the FDA and health authorities in most other countries approved its use only for treatment-resistant schizophrenia, and required regular haematological monitoring to detect granulocytopenia, before agranulocytosis develops. In December of 2002, Clozapine was also approved for reducing the risk of suicide in schizophrenic or schizoaffective patients judged to be at chronic risk for suicidal behavior.

Commonly approved indications

  • Treatment-resistant schizophrenia, if the required hematologic monitoring is adhered to
  • Reducing the risk of suicide in schizophrenic or schizoaffective patients judged to belong to a high risk group with chronic risk for suicidal behavior. Clozapine was shown to prolong the time to suicidal attempt significantly greater than Olanzapine (Zyprexa®).

Clozapine works equally well against positive (e.g. delusions, hallucinations) and negative (e.g. emotional and social withdrawal) symptoms of schizophrenia. It has no dyscognitive effect often seen with other psychoactive drugs and is even able to increase the capabilities of the patient to react to this environment and thereby fosters social rehabilitation.

Off-label and investigational drug use

  • Treatment of psychosis in L-Dopa treated patients (25 to 50 mg at bedtime is often sufficient); this indication is currently approved in Switzerland
  • Treatment of otherwise resistant acute episodes of mania
  • Treatment of psychotic symptoms occurring in patients with dementia of the Levy-body-type
  • Treatment of severe cases of obsessive compulsive disorder
  • Treatment of intractable chronic insomnia, if all other measurements have failed

Though much research has been done evaluating the benefit of clozapine in treating the aforementioned conditions, it is too early to come to a conclusive result. If you contemplate clozapine as drug for these conditions, weigh carefully benefits and risks and inform the patients fully, if possible, about the advantages and risks of clozapine treatment, before a joint decision is made. If the patient is not able to make own decisions, parents or guardians or the competent court must give their consent.

Chemistry

Clozapine is yellow crystalline solid with melting point 183-184 °C. It is insoluble in water, soluble in acetone, very well soluble in chloroform. Chemical name is <8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzodiazepine>.

Read more at Wikipedia.org


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Atypical Antipsychotic Drug Warning
From Nurse Practitioner, 7/1/04

The Food and Drug Administration (FDA) has asked all manufacturers of atypical antipsychotic medications to add a warning statement to the products' labeling describing the risk of hyperglycemia and diabetes associated with their use. This class of medication includes aripiprazole (Ability), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).

The warning advises that hyperglycemia has been extreme in some cases, and associated with ketoacidosis or hyperosmolar coma, or death. The relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased risk of diabetes in patients with schizophrenia and the increasing incidence of diabetes in the general population, but studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients using atypical antipsychotic drugs.

Patients with an established diagnosis of diabetes who start taking atypical antipsychotic drugs should be monitored regularly for worsening glucose control. Patients with risk factors for diabetes who are starting treatment with atypical antipsychotic medications should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.

Copyright Springhouse Corporation Jul 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

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