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1975, after reports of agranulocytosis leading to death in some clozapine-treated patients, Clozapine was voluntarily withdrawn by the manufacturer.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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Meds are no defense against suicide - Health - Brief Article
From Psychology Today, 9/1/02 by Kaja Perina

Psychotropic medications successfully combat symptoms of depression, anxiety and psychosis but fail spectacularly in reducing one crucial index of mental illness: suicide. A review of more than 71,000 patients in clinical trials of 52 psychotropic medications found an equal risk of suicide among those assigned medication and those taking placebos.

"Suicide may not be connected to alleviating symptoms [of mental illness]," says Arif Khan, M.D., medical director of the Northwest Clinical Research Center in Bellevue, Washington. "It is a complex behavior, much more complicated than the treatments for mental illness."

Khan reviewed Food and Drug Administration (FDA) reports on psychotropic drugs approved between 1985 and 2000 and calculated that the risk of suicide--11 per 100,000 in the general population--jumps to 752 per 100,000 in antipsychotic trials and 655 per 100,000 in trials of antidepressants. Khan also reviewed anti-panic, anti-anxiety and anti-obsessional agents. No class of medication showed a significant difference in the risk of suicide or attempted suicide among patients assigned to trial medication, FDA-approved medication or placebo.

Because clinical trials exclude patients thought to be at risk for suicide, or those suffering from comorbid mental illness, the rate of suicide calculated by Khan is surprisingly high. However, in general patients on placebos tend to drop out of trials earlier than those on medication, comparatively elevating the rate of suicide among patients taking psychotropic medication.

"Further research to identify psychotropics or other treatments that reduce suicide risk is essential" says Khan, who presented his findings at the New Clinical Drug Evaluation Unit, an annual meeting sponsored by the National Institute of Mental Health.

The atypical antipsychotic clozapine (marketed as Clozaril), is the sole medication currently under review by the FDA for use as an anti-suicidal agent.

COPYRIGHT 2002 Sussex Publishers, Inc.
COPYRIGHT 2002 Gale Group

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