Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia

Steady-state blood clozapine concentrations in 58 schizophrenic patients 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 responders from nonresponders. After 4 weeks of treatment, only 8% of those patients with a blood clozapine concentration < 420 ng/mL responded compared with 60% of those who had a blood clozapine concentration > 420 ng/mL. When plasma concentrations were increased above 420 ng/mL (by a double-blind random assignment procedure), nonresponders increased their response rate to 73% if their plasma concentrations at Week 12 exceeded 420 ng/mL compared with a response rate of 29% if their Week 12 levels remained below 420 ng/mL (chi 2 = 4.2, p < .04).