Is there an association between the effects of clozapine on the production of reactive oxygen metabolites by blood monocytes and clinical outcome in neuroleptic-resistant schizophrenia?

Abstract

The production of reactive oxygen metabolites (ROM) by monocytes (MO) and polymorphonuclear leukocytes (PMNL) from eight patients with neuroleptic-resistant schizophrenia was measured before and after 3 and 10 weeks of clozapine (CLO) treatment. Although ROM production did not show significant longitudinal trends during the trial, the changes in ROM production by non-stimulated (Mon) and phorbol myristate acetate (PMA)-stimulated MO (MOs) at week 3 (values at base-line minus those at week 3) correlated positively (r=0·743, p=0·035, and r=0·838, p=0·009, respectively) with the changes on the total Positive and Negative Syndrome Scale (PANSS) scores, i.e. a decrease or relatively small increase in the ROM production by MOn and MOs was associated with more favourable clinical outcome than a clear-cut increase in their ROM production. The serum concentrations of CLO at week 3 also correlated positively with the changes in ROM production by MOs at week 3 (r=0·761, p=0·047) and at week 10 (r=0·985, p<0·001). A possible causal relationship between these observations and the mechanism of action of CLO is discussed. © 1998 John Wiley & Sons, Ltd.