Clozapine, cancer chemotherapy and neutropenia - dilemmas in management

Clozapine is the antipsychotic of choice in the management of treatment resistant schizophrenia. Neutropenia is a rare but serious adverse effect of clozapine. The risk for neutropenia with clozapine is highest in the first 18 weeks of treatment and decreases with time though a few cases were reported after several years of continued therapy. Different protocols that guide the monitoring for neutropenia have been developed; in Australia we follow the protocol implemented through the Clopine® Alert Programme. Despite an increased risk of poor physical health and shortened life span in patients with schizophrenia, the overall incidence of cancer in schizophrenia is not significantly increased. This suggests a discrepancy between cancer risk exposure (e.g., smoking) and cancer incidence in schizophrenia (Goldacre et al. 2005), an association that has been described paradoxical (Hodgson et al, 2010). Nevertheless, these two conditions co-occur (Goldacre et al. 2005). It can create difficulties in management when the patient is clinically stable on clozapine and require chemotherapeutic agents that can frequently cause myelosuppression and neutropenia as it can pose several dilemmas for the clinicians. A systematic literature search identified 11 case-reports (Avnon & Stolerman 1993, Bareggi et al. 2002, Frieri et al. 2008, Goulet & Grignon 2008, Haut 1995, Hundertmark and Campbell 2001, Kolli et al. 2012, McKenna et al. 1994, Rosenberg et al. 2007, Rosenstock 2004, Wesson et al. 1996). The results are summarized in Table 1. Interestingly, Clozapine was successfully continued during chemotherapy treatment regime in most of these cases despite neutropenia (Bareggi et al. 2002, Goulet & Grignon 2008, Kolli et al. 2012, Rosenberg et al. 2007, Rossenstock 2004, Wesson et al. 1996). There is however little guidance to appropriately manage the potential risks under these circumstances (Rosenstock 2004). We present here three cases and discuss three of the dilemmas that clinicians can face under such circumstances- identifying the offending agent, decision to continue clozapine treatment and use of human granulocyte colony stimulating factor (G-CSF)