Drug blood levels, influencing factors and their relationship with metabolic parameters in patients with schizophrenia using clozapine

Abstract

Clozapine stands out as the superior antipsychotic for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) for clozapine can potentially reduce side effects, enhance treatment compliance, and ensure optimal therapeutic response. This study aimed to measure clozapine blood levels, to determine the factors affecting blood levels, and to investigate the relationship with metabolic values. This study included 80 patients with schizophrenia. Clinical assessments were conducted using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI), and the UKU Side Effect Rating Scale. Measurements included waist circumference, body weight, height, blood pressure, routine complete blood count, and biochemical data. Serum clozapine and its metabolite norclozapine levels were measured by liquid chromatography-mass spectrometry (LC/MS-MS). Elevated clozapine blood levels, exceeding the recommended therapeutic range, were observed in 71.25 % of patients despite normal dosing. Body weight, body mass index (BMI), waist circumference, triglyceride, and total cholesterol levels were high in patients with high clozapine blood levels. Female patients had higher norclozapine levels than males. Although clozapine blood levels did not significantly differ between smokers and non-smokers, the concentration-to-dose ratio was higher in smokers. Metabolic side effects can be reduced by keeping clozapine blood levels within the therapeutic range by adjusting the individualized dosing by considering the characteristics, such as gender and smoking status of patients with schizophrenia using clozapine. Appropriate therapeutic blood levels may be achieved by using lower doses of clozapine in the Turkish population.