Predicting clinical response to clozapine treatment by plasma level

The relationship between plasma level of clozapine and clinical response, and whether an increase in plasma level in non-responders would enhance the response rate was examined. Fifty-eight treatment resistant schizophrenic patients completed a 12 week fixed-dose, double blind trial. Steady-state plasma clozapine concentrations varied more than 45 fold after fixed-dose treatment (400 mg/day). Discriminant function analysis determined that a plasma level of 420 ng/mL optimally distinguished responders from non-responders. At week 4 only 8% of those patients with a plasma level below 420 ng/mL responded compared with 60% of those who had a plasma level above 420 ng/mL. When plasma levels were increased above 420 ng/mL (by a double-blind random assignment procedure), non-responders increased their response rate to 73% if their plasma level exceeded 420 ng/mL at week 12, compared to 29% if week 12 levels remained below 420 ng/mL (p<0.04).