Relationships between clozapine and norclozapine plasma concentrations, clozapine dose, and clinical response in Tunisian patients with schizophrenia-treatment resistance

The present study investigated relationships between clozapine dose, clozapine and norclozapine plasma concentrations, and clinical responses to clozapine treatment in Tunisian schizophrenics. Fourteen schizophrenia-treatment resistant patients, recruited for this study, were treated with clozapine for 45 days. Patient health improvement was assessed before and after each cycle of two weeks of clozapine therapy, using the Brief Psychiatric Rating Scale (BPRS). Plasma clozapine and norclozapine concentrations were determined by high-performance liquid chromatography (HPLC). No significant correlations between plasma clozapine and norclozapine concentrations and clinical health improvement among our schizophrenic patients were found. However, a significant correlation was observed between clinical health improvement given by BPRS scores and norclozapine plasma concentration to daily clozapine dose ratio (NCZ/D). Despite the small sample size of our study, our findings suggest that the clozapine therapy response variations observed in our patients may be, in part, explained by the interindividual differences in plasma norclozapine concentration to clozapine dose ratio (NCZ/D). So the NCZ/D parameter could be used as a good indicator for adjusting the clozapine dose-adaptation strategy and consequently for improving the clinical psychopathological state of schizophrenia-treatment resistant patients.