Schizophrenia Drug Emerging from Under a Cloud

Shortly after its introduction in 1974, clozapine, a ‘second-generation’ drug for treating schizophrenia, was withdrawn by the manufacturers. This was because of its tendency to cause fatal agranulocytosis, which seemed to be more common with clozapine than other antipsychotic drugs.

Gradually, over the years, clozapine has been rehabilitated; it was finally marketed in the USA in 1990. There are strict requirements in most countries for frequent white blood cell counts, especially during the early months of treatment, in order to detect any signs of granulocytopenia in as early a stage as possible, and be able to take appropriate action. Successor drugs have come (and gone), without obvious improvements in antipsychotic activity.

This month The Lancet has published a report from Finland on 11-year follow-up of schizophrenic patients under treatment. (Ironically, it was in Finland that the ‘outbreak’ of clozapine-related agranulocytosis cases was first reported, 34 years ago.) And the surprising finding from this new study? I quote the authors: “Clozapine seems to be associated with a substantially lower mortality than any other antipsychotics. Restrictions on the use of clozapine should be reassessed.”

One must realize that the use of clozapine requires frequent lab tests, which may have influenced mortality over the years; most other antipsychotics aren’t handicapped by the need for such close monitoring. However, the aim is to achieve the lowest mortality possible, even if this means extra lab tests, etc. From this viewpoint, clozapine ‘fills the bill’.