Management of clozapine-associated neutropenia

SUMMARY Clozapine is the only evidence-based intervention for treatment-resistant schizophrenia. One of the drug's most well-known and potentially fatal adverse effects is agranulocytosis (severe neutropenia). Hence, regular blood tests are an essential component of clozapine treatment. This article presents a narrative review of the history, incidence, potential aetiology and management of clozapine-associated neutropenia. It gives an overview of clozapine monitoring requirements, including those for benign ethnic neutropenia. We point to the growing body of evidence that the risk of clozapine-induced agranulocytosis is mostly confined to the first year of treatment and that the risk of fatality is considerably lower than previously assumed. Given the absence of alternative evidence-based interventions for treatment-resistant schizophrenia, we suggest that rechallenging with clozapine should be considered in most patients with clozapine-associated mild to moderate neutropenia who do not respond to other treatments. A more careful risk–benefit analysis is needed in cases of severe neutropenia (agranulocytosis).