Antipsychotics agranulocytosis with

Blood Dyscrasias Mild leukocytosis, leukopenia, and eosinophilia occasionally occur with antipsychotic treatment, particularly with clozapine and less often with phenothiazines of low potency. It is difficult to determine whether leukopenia that develops during the administration of such agents is a forewarning of impending agranulocytosis. This serious comphcation occurs in not more than 1 in 10,000 patients receiving chlorpromazine or other low-potency agents (other than clozapine) it usually appears within the first 8-12 weeks of treatment. 

Clozapine is an atypical antipsychotic that is usually used in patients who are inadequately controlled with other antipsychotics. The reason is that clozapine is associated with a risk of potentially fatal agranulocytosis. As with other atypicals, side-effects of clozapine include occurrence of hyperglycaemia and diabetes. 

Clozapine is considered to be the gold standard of treatment of schizophrenia with patients usually moving onto it after treatment failure with two other antipsychotics. Yet the history of it is quite chequered. When it was first introduced onto the European market in 1975 it was used freely with no restrictions on use. Following the death of eight patients in Finland from agranulocytosis, a very rare (< 1 %) but often fatal condition occur-ing normally within the first few months of use, it was voluntarily taken off the market. 

Agranulocytosis Because of a significant risk of agranulocytosis, a potentially life-threatening adverse reaction, reserve clozapine for use in the treatment of severely ill schizophrenic patients who fail to show an acceptable response to adequate courses of standard antipsychotic drug treatment because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with clozapine, it... 

The risk of agranulocytosis and seizures limits use to patients who have failed to respond or were unable to tolerate treatment with appropriate courses of standard antipsychotics. 

Clozapine was the first atypical antipsychotic released in the United States. However, clozapine is associated with the risk of leukopenia and, potentially, lethal agranulocytosis. Because of these concerns, hematological monitoring during clozapine pharmacotherapy is required (Alphs and Anand, 1999). Due to these hematological risks, clozapine is indicated only for patients with treatment-resistant schizophrenia. The other atypical antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone, that are marketed in the United States can be used as first-line treatments for adults with schizophrenia. 

The choice of antipsychotic medication is often determined, in large part, by anticipated side effects. In most circumstances, atypical antipsychotics (except for clozapine) are best tolerated and are preferred as first-line agents. Clozapine is generally reserved for patients with refractory iUness because of the risk of agranulocytosis. 

Clozapine, the first of the class of atypical antipsychotic drugs, rarely causes EPS, and it is the only antipsychotic drug that is not associated with treatment-emergent tardive dyskinesia. Because of the approximately 1% risk of potentially fatal agranulocytosis, the use of clozapine is restricted to patients who have not responded to or cannot tolerate other antipsychotic drugs. 

Various combinations of mood stabilizers and antipsychotics may then be considered, always in a stepwise strategy. Although clozapine may be combined with lithium and/or VPA, we caution against the combined use of clozapine plus CBZ, given the former s propensity to induce agranulocytosis and the latter s ability to suppress bone marrow production. 

Agranulocytosis, cholestatic jaundice, and skin eruptions occur rarely with the high-potency antipsychotic drugs currently used. 

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