Characterization and clinical management of clozapine-induced fever

To characterize clozapine-induced fever and suggest clinically relevant management recommendations.

Literature was accessed through MEDLINE (1966-June 2007) using the terms clozapine, fever, and adverse effects. In addition, reference citations from publications identified were reviewed.

All English-language articles about human studies of fever associated with the use of clozapine were evaluated.

Mild to high-grade fever frequently accompanies clozapine therapy. Fever usually occurs within 10-15 days after treatment initiation and has been reported to last between 2 and 4 days. The mechanism and clinical implications of clozapine-induced fever are unclear. The primary concern for clinicians, with regard to these fevers, is the possibility of 2 serious conditions: agranulocytosis with infection or neuroleptic malignant syndrome (NMS). However, the presence of fever during clozapine therapy does not appear to predict agranulocytosis, NMS, or an increased rate of drug discontinuation at 1 year.

Available data suggest that clozapine-induced fevers are benign; once infectious and other medical causes for fever are ruled out, clozapine therapy can be continued.