Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring.
OBJECTIVE
To provide information for physicians and patients on which to base a decision as to whether to stop mandatory blood testing.


METHODS
Articles on drug-induced blood dyscrasias were identified by searches of MEDLINE (1966-September 2005) and review of their bibliographies. Novartis was asked to provide additional data on clozapine, leukopenia, agranulocytosis, and suicidality.


METHODS
Data on the chance of clozapine-induced leukopenia and agranulocytosis were combined with data about possible fatality and compared with the risks associated with other medications and with life in general.


RESULTS
The chance of clozapine-induced leukopenia or agranulocytosis decreases exponentially over time. In the US, the chance in the second 6 months of treatment is 0.70/1000 patient-years and, after the first year, 0.39/1000 patient-years. The case fatality rate of clozapine-induced agranulocytosis is estimated as 4.2-16%, depending on whether a granulocyte colony-stimulating factor is used. Nevertheless, treatment with clozapine reduces overall mortality, probably because it reduces suicidality.


CONCLUSIONS
After at least 6 months' treatment with clozapine, the mortality involved in stopping white blood cell monitoring is about the same as the mortality associated with other medications, such as mianserin or phenylbutazone, and with life in general (traffic or occupational accident). If the patient has been well informed and wishes to stop the monitoring, it is a medically justifiable option to do so and is preferable to stopping treatment with clozapine since this drug reduces overall mortality.
Schulte
Peter  F J
P
Mental Health Services North-Holland North, Department De Dijk, Kennemerstraatweg 464, 1851 NG Heiloo, Netherlands. r.schulte@ggz-nhn.nl
D000380:Agranulocytosis / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology*; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D016239:MEDLINE; D008991:Monitoring, Physiologic / Q000592:standards; D012306:Risk
D014150:Antipsychotic Agents; D003024:Clozapine