Abstract

To the Editor: In the July 2008 issue of the Journal, the Clinical Case Conference by Sharmin Ghaznavi, M.D., Ph.D., et al. (1) provided a good example of a treatment plan and discussed three major clozapine-related issues pertaining to 1) the risk of neutropenia/agranulocytosis and seizures, 2) drug-drug interaction, and 3) the use of anticonvulsants in the prophylaxis of seizures. For many years, the authors’ patient was treated with clozapine, 750–800 mg/day, and valproic acid, 1500 mg/day, was added later. During these regimens, the patient’s white blood cell and neutrophil counts remained normal. At some stage, donepezil was added, and the patient, for the first time, presented with decreased white blood cell and neutrophil counts. In addition, the patient showed a marked decrease in his white blood cell and neutrophil counts when clozapine, 500 mg/day, was added to a regimen of valproic acid, 1500 mg/day, and risperidone, 6 mg/day. Before the addition of clozapine and following the discontinuation of the drug, the patient’s white blood cell and neutrophil counts were normal. Dr. Ghaznavi et al. concluded that the occurrence of neutropenia/agranulocytosis in both instances was not actually clozapine-induced. However, we feel that an alternative interpretation is more likely.