Formation of immature neutrophil leucocytes in schizophrenic patients treated with various antipsychotic drugs: comparisons and predictions

The neutrophils of schizophrenic patients taking antipsychotic drugs were evaluated. Neutrophil immaturity was assessed by determining mean nuclear lobe number in peripheral blood smears of patients and controls. Subjects were patients medicated with typical (flupenthixol (n = 6), fluphenazine (n = 7), haloperidol (n = 23), thioridazine (n = 15), and trifluoperazine (n = 6)) or atypical (olanzapine (n = 15), risperidone (n = 10), and sulpiride (n = 7)) antipsychotic drugs. Controls (n = 58) were healthy, non-medicated clinical and academic staff. Mean lobe number was determined using Light microscopy and examining 300 neutrophils per individual. For subject and control groups, means and medians of mean Lobe numbers, and also mean white cell and neutrophil counts, were determined. Means for each group were compared using the Mann-Whitney U test; variances using F ratios. Mean Lobe numbers of all patients were decreased compared to controls. The left shift occurring in patients medicated with haloperidol, olanzapine, risperdone, thioridazine, and trifluoperazine was significant at P < 0.0001; for flupenthixol P < 0.001, and for sulpiride P < 0.05. The left shift for fluphenazine was not statistically significant. For one patient, mean Lobe numbers were obtained before and after medication seen. Although the coefficient of variation in the patient groups was large compared to the controls, nevertheless more than half of the patients had mean Lobe numbers outside the observed range of values seen in the control population. White blood cell and neutrophil counts in patients and controls were not significantly different. This study demonstrated that patients taking antipsychotic drugs have immature neutrophils, but normal total white cell and neutrophil numbers. The effect was seen with both typical and atypical antipsychotic drugs, and is probably drug-induced. It is possible that mean Lobe number may predict patients at risk from neutropenia or agranulocytosis, as is also suggested by an analysis of the relative numbers of literature reports of neutrophil pathology for these drugs. It is of interest that olanzopine, which has been considered a haematologically non- hazardous drug, was shown to be associated with a significant decrease in mean Lobe number.