Therapeutic drug monitoring of clozapine in schizophrenic outpatients

Abstract

In the acute therapy of treatment-resistant schizophrenic patients a lower threshold of 350ng/ml clozapine is considered as optimal for response. For stabilization of outpatients under long-term treatment, however, literature based recommendations are so far lacking. This study analysed clozapine plasma levels parameters of schizophrenic outpatients with an F20.x diagnosis according to ICD-10 from a primary care unit treated with clozapine treated under a naturalistic conditions. Plasma levels were measured over a time of 27 months or until the first rehospitalisation. Seven of the 24 observed patients relapsed during this time. Patients who relapsed had a significantly lower median plasma level (344 vs. 481ng/ml, p=0.000). The median daily clozapine dose was 250mg in both groups (p=0.365). The average coefficient of variation of clozapine plasma concentrations was lower in subjects without re-hospitalization (29.2% vs. 41.7%), but not significant (p=0.112). Another remarkable result was that only one of the 7 patients treated with fluvoxamine augmentation strategy relapsed during the study. It is concluded that also under long-term treatment with clozapine sufficiently high plasma levels are needed. Moreover, TDM-controlled pharmacotherapy is helpful for sustainable long-term treatment to prevent relapses and re-hospitalizations. Augmentation with fluvoxamine might be an option to improve the stabilization which needs further investigations.