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

Reactive oxygen metabolites (ROM), produced by mononuclear phagocytes may p articipate in brain pathology. Clozapine (CLO) may modulate cell immunity, and it is also superior to conventional neuroleptics in conditions with a p utative impact of oxidative damage by ROM, i.e. negative symptoms and neuro leptic-resistance in schizophrenia, and tardive dyskinesia. In line with a hypothesis of a possible impact of the phagocyte-produced ROM in schizophre nia, we measured the ROM production by in vitro CLO-incubated blood phagocy tes from eight patients With neuroleptic-resistant schizophrenia at weeks 0 , 3, and 10 of a clinical CLO trial. The ROM production by nonstimulated mo nocytes (MOn) decreased after incubation in vitro with CLO at weeks 0 (base line) and 3, with a similar trend seen also at week 10 of the trial. The ma gnitude of this decrease at week 0 correlated positively with subsequent im provement in clinical symptomatology (R-2 = 0.789, p = 0.003 for negative s ymptoms 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. Copyri ght (C) 1999 John Wiley & Sons, Ltd.