Circadian rhythm of white blood cells during clozapine treatment

Rationale: The atypical antipsychotic clozapine is effective in the treatment of patients with refractory schizophrenia. It carries a well-known risk of neutropenia and agranulocytosis, which necessitates the immediate discontinuation of clozapine. Objective: We report a patient who developed neutropenia on clozapine, but behind the cell count decrease showed to be a diurnal variation of the white blood cells (WBC). Methods: Due to the lack of efficacy of subsequent treatment of conventional and other atypical neuroleptics, treatment with clozapine was restarted after discontinuation. When the morning count of WBC began to fall, WBC count was repeated in the afternoons. Results: Careful blood cell monitoring showed a pronounced diurnal variation of WBC (2.9–4.2×10⁹/l in the morning and 3.6–7.1×10⁹/l in the afternoon) and granulocytes (0.8–1.4×10⁹/l and 2.9–5.5×10⁹/l, respectively). Conclusions: Some patients may thus have a spuriously low cell count and may be unnecessarily denied effective treatment. Received: 10 February 1999 / Final version: 22 March 1999