Abstract
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.
Highlights
Clozapine (CZ) is a second-generation antipsychotic drug
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)
The CZ plasma concentration parameter, which is used as an indicator of the treatment response and dose adaptation, shows no significant correlation with the health state improvement given by Brief Psychiatric Rating Scale (BPRS) scores (r = 0.0989; p < 0.737) (Figure 1)
Summary
Clozapine (CZ) is a second-generation antipsychotic drug It is primarily used in the treatment of schizophreniatreatment resistant psychopathology. Treatment with clozapine is associated with several side effects that complicate the use of the drug and necessitate therapeutic monitoring [1,2]. This monitoring allows the optimization of the therapeutic dose-response efficacy and the prevention of excessive toxicity of CZ, reducing in this way the risk of relapse [3,4,5]. The mechanism underlying the differences in clozapine treatment response is not well known Some studies attribute these differences to patients’ sex, age, body weight, and physiology [8]. It may be possible that the metabolic polymorphism of clozapine elimination, attributed to genetic and/or environmental origins, modifies clozapine plasma concentration and elimination and its psychotherapeutic effects
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