Pancytopenia on switching from clozapine to olanzapine: A case report and some unresolved issues

The newer antipsychotics olanzapine and clozapine share a number of structural and functional similarities. However, unlike clozapine, which induces agranulocytosis in about 1% of treated patients, olanzapine is not normally known to cause hematological adverse effects. The hematological effects of olanzapine have been scrutinized in several trials, none of which have found any evidence of hemotoxicity, or effects different from placebo in this regard. These studies have included a trial of 32 olanzapine-treated patients who had previously experienced clozapine-induced agranulocytosis. Olanzapine proved to be safe even in this group. On the other hand, several cases of olanzapine-related agranulocytosis/ neutropenia in patients who had received clozapine previously, have also been reported. 2-4 Such hematological side-effects have been proposed to be due to the propensity of olanzapine to prolong neutropenia in patients who developed it with clozapine, or to re-induce it in patients who have recovered from clozapine-induced neutropenia. A residual effect of clozapine or the direct effects of olanzapine are some of the other possibilities. The safe timeframe between the two medications and the risk of neutropenia remains unclear. Such timeframes have usually ranged from a few days to weeks, but periods up to three years have also been reported. Some reports have also hinted at a relationship between the dose of olanzapine and the degree of neutropenia but this has never been confirmed. On the whole the number of such reports is still very small and not a single report has been able to demonstrate a causal association with the drug. Nevertheless, such incidences are particularly significant because they suggest the need for caution while switching from clozapine to olanzapine. The following is a description of one such instance.