Blood dyscrasias in clozapine-treated patients in Italy.
OBJECTIVE
Clozapine is a dibenzodiazepine derivative that is more effective than standard neuroleptic drugs in refractory schizophrenic patients, but its introduction in some countries was delayed by its propensity to cause blood dyscrasias. However, over the last ten years, different reports have clearly demonstrated that agranulocytosis and neutropenia can be easily prevented by means of strict hematologic surveillance. This article reviews the results of the first five years of the Italian Clozapine Monitoring System (ICLOS).


METHODS
The hematologic parameters of 2,404 patients registered between 1995 and 1999 were collected in a central database, before the patients began clozapine-treatment, weekly for the first 18 weeks, and then monthly throughout the duration of therapy. On the basis of conventional criteria, different risk levels have been identified with total leukocyte <3. 0x10(9)/L and/or an absolute neutrophil count <1.5x10(9)/L leading to immediate discontinuation of the drug.


RESULTS
The analysis shows that 0.9% of the patients developed neutropenia and 0.7% agranulocytosis, mainly during the first 18 weeks of clozapine treatment. Drug discontinuation led to the normalization of hematologic parameters in all cases, and the use of growth factors reduced the risk of infectious complications. Transient leukocytosis and eosinophilia were also observed but these did not have any serious clinical effects.


CONCLUSIONS
The ICLOS study confirms that regular hematologic monitoring is highly effective in minimizing the incidence of clozapine-associated blood dyscrasias. The lower than initially expected rates of agranulocytosis and associated deaths are encouraging in view of the benefits of this drug in treatment-resistant schizophrenia and other neurologic disorders.
Lambertenghi Deliliers
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Dipartimento di Scienze Mediche, Ospedale Maggiore IRCCS, via Francesco Sforza 35, 20122 Milan, Italy. giorgio.lambertenghi@unimi.it
D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced / Q000453:epidemiology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D004802:Eosinophilia / Q000139:chemically induced; D005260:Female; D018756:GABA Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007558:Italy; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D010265:Paraproteinemias / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced
D014150:Antipsychotic Agents; D018756:GABA Antagonists; D012702:Serotonin Antagonists; D016179:Granulocyte Colony-Stimulating Factor; D003024:Clozapine