We investigated the relationship between plasma clozapine concentrations and clinical response in treatment-refractory schizophrenic patients. In a previous study, we found that plasma drug concentrations above 350 ng/mL maximized clinical response in a group of 29 patients. This study represents a follow-up of these original 29 patients over approximately 2 1/2 years of clozapine treatment. We found that during the initial 6-week trial of clozapine, 38% (N = 11) of the patients were considered to be responders. With continued treatment, we found that 58% (14 of 24) were classified as responders. Consistent with our previous study, we observed that plasma concentrations were helpful in predicting response. Five of 7 patients who had unsatisfactory response became responders when their plasma clozapine concentrations increased to above 350 ng/mL. We conclude that the assessment of plasma clozapine concentrations as a guide to dose adjustment may be useful in maximizing response.
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