PLASMA CLOZAPINE CONCENTRATIONS PREDICT CLINICAL-RESPONSE IN TREATMENT-RESISTANT SCHIZOPHRENIA

Steady-state blood clozapine concentrations in 58 schizophrenic patien ts varied more than 45-fold (40-1911 ng/mL) after fixed-dose treatment (400 mg/day). Discriminant function analysis determined that a blood clozapine concentration of 420 ng/mL optimally distinguished responder s from nonresponders. After 4 weeks of treatment, only 8% of those pat ients with a blood clozapine concentration < 420 ng/mL responded compa red with 60% of those who had a blood clozapine concentration > 420 ng /mL. When plasma concentrations were increased about 420 ng/mL (by a d ouble-blind random assignment procedure), nonresponders increased thei r response rate to 73% if their plasma concentrations at Week 12 excee ded 420 ng/mL compared with a response rate of 29% if their Week 12 le vels remained below 420 ng/mL (CHI2 = 4.2, p < .04).