Clozapine-induced decrease in the production of reactive oxygen metabolites by monocytesin vitro may predict clinical response to clozapine in treatment-resistant schizophrenia

Abstract

Reactive oxygen metabolites (ROM), produced by mononuclear phagocytes may participate in brain pathology. Clozapine (CLO) may modulate cell immunity, and it is also superior to conventional neuroleptics in conditions with a putative impact of oxidative damage by ROM, i.e. negative symptoms and neuroleptic-resistance in schizophrenia, and tardive dyskinesia. In line with a hypothesis of a possible impact of the phagocyte-produced ROM in schizophrenia, we measured the ROM production by in vitro CLO-incubated blood phagocytes from eight patients with neuroleptic-resistant schizophrenia at weeks 0, 3, and 10 of a clinical CLO trial. The ROM production by non-stimulated monocytes (MOn) decreased after incubation in vitro with CLO at weeks 0 (baseline) and 3, with a similar trend seen also at week 10 of the trial. The magnitude of this decrease at week 0 correlated positively with subsequent improvement in clinical symptomatology (R2=0·789, p=0·003 for negative symptoms at week 3 of the trial). We conclude that the sensitivity of MOn to the in vitro effect of CLO on their ROM production may be predictable for the clinical response to CLO in neuroleptic-resistant schizophrenia. Copyright © 1999 John Wiley & Sons, Ltd.