Effect of Clonazepam Co-Administered with Clozapine on the Serum Clozapine and Norclozapine Concentration of Patients with Schizophrenia: A Retrospective Survey

BACKGROUND: For patients with schizophrenia clozapine (CLZ) is sometimes co-prescribed with clonazepam (CLNAZ). However, the impact of administration of CLZ along with CLNAZ on the serum concentration of CLZ and its major metabolite N-CLZ in schizophrenia is not well understood. AIM: To investigate the effects of CLNAZ co-medication, patient gender, age and CLZ dosage on serum concentration of CLZ and norclozapine (N-CLZ) in individuals with schizophrenia. METHODS: Serum CLZ and N-CLZ concentrations and demographic data were retrospectively analyzed for 341 patients with schizophrenia. We used SPSS 21.0 to perform stepwise regression to analyze the concentration data and demographics. Variables included in the analysis were: serum concentration of CLZ, N-CLZ, and CLZ dosage, gender, age and CLNAZ co-medication. RESULTS: (1) CLNAZ co-medication significantly affects serum CLZ and N-CLZ concentration in schizophrenics (p=0.010, p=0.020); (2) CLNAZ co-medication, gender and CLZ dosage significantly affect serum CLZ concentration in patients with schizophrenia (p=0.010, p=0.009, p<0.001). Serum CLZ concentration is negatively correlated with CLNAZ co-medication, and is positively correlated with being female and CLZ dosage; (3) CLNAZ co-medication and CLZ dosage were significantly related to serum N-CLZ concentration in participants (p=0.020, p<0.001). Serum N-CLZ concentration was negatively correlated with CLNAZ comedication, and positively correlated with CLZ dosage. CONCLUSION: CLNAZ co-medication is associated with changes in serum CLZ and N-CLZ concentration. It is indicated that gender and/or CLZ dosage are also related to serum CLZ and N-CLZ concentration. Therapeutic drug monitoring and dosage regulation of CLZ should be performed for patients with schizophrenia who are also taking CLNAZ to maintain a safe and effective serum concentration of CLZ and N-CLZ.