Miriam Naheed, Ben Green


Curr Med Res Opin. 2001;17(3) 

In This Article

Summary and Introduction


Clozapine is a dibenzodiazepine derivative and a truly atypical anti-psychotic. Its therapeutic effects are probably mediated by dopaminergic and serotonergic activity. Although it appears to be the most effective antipsychotic drug for treatment-resistant schizophrenia, its general use is limited because of the risk of agranulocytosis.


Clozapine is manufactured by Novartis pharmaceuticals and marketed under the trade name of Clozaril. Its structural formula is given in Figure 1. It is an atypical anti-psychotic agent whose mode of action is thought to pertain to its interaction with dopaminergic and serotonergic neurotransmitter systems. Its clinical efficacy may depend on plasma clozapine concentrations, but its response rate varies widely. The response rate is anywhere between 30% and 100% of patients on short-term therapy, whereas, during long-term treatment, 60% of patients unresponsive to, or intolerant of, previous antipsychotics respond to clozapine. Significant improvements in both positive and negative psychotic symptoms, quality of life, social functioning and suicidality have been demonstrated. It represents the first major advance in the treatment of schizophrenia since the advent of antipsychotics in the 1950s.

Figure 1.

The structure of clozapine.

Although clozapine has been found to be the most effective antipsychotic drug for treatment-resistant schizophrenia, its use has been greatly limited because of the risk of agranulocytosis, which has, in fact, been shown to have a frequency which is less than 1%[1]. In balancing benefits against risks, it is worth noting that the suicide mortality rate in patients with schizophrenia not treated with clozapine is much higher than the mortality from agranulocytosis in the patients treated with clozapine[2,3]. With periodic blood monitoring, the agranulocytosis risk is 0.38%[1].


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