Study on the daily dose and serum concentration of clozapine in psychiatric patients and possible influencing factors of serum concentration

Abstract

Background: Clozapine is the most effective drug for treatment-resistant schizophrenia, and the dosage and concentration of clozapine in the treatment of mental illness vary greatly in different populations and are affected by many factors.

Methods: The serum clozapine concentration of 3734 psychiatric patients was detected, and data on daily dose, sex, age and other medical records were collected for statistical analysis.

Results: The mean daily dose, mean serum concentration and mean C/D (concentration/dose) ratio of clozapine were 191.02 ± 113.47 mg/day, 326.15 ± 235.66 ng/mL and 1.94 ± 1.25 ng/mL per mg/day, respectively. There was difference in daily dose between sexes, and females had higher daily dose (p <0.01), higher serum clozapine concentrations (p < 0.01) and higher C/D ratios (p < 0.01). There were significant differences in daily dose (p < 0.001), serum drug concentration (p < 0.001) and C/D ratio (p < 0.001) among different age groups. The daily dose decreased with age (p for trend < 0.001), and the C/D ratio increased with age (p for trend < 0.001). Inpatients and outpatients had no difference in daily dose, but inpatients had higher serum concentration (p < 0.001) and C/D ratio (p < 0.001). There was no difference in daily dose among different occupations, but there were significant differences in serum concentration (p < 0.001) and C/D ratio (p < 0.001), and unemployed patients may have higher serum concentration and C/D ratio. Duration of disease, comorbidity, marital status, and psychotic type may influence the daily dose and serum concentration.

Conclusions: The effective daily dose and serum concentration of clozapine in the study area may be lower than recommended levels, and women have higher serum concentrations and slower metabolic rates. With increasing age, the daily dose decreases, and the metabolic rate slows. Inpatient status and occupation of patients may influence the serum concentration and metabolic rate of clozapine.

Keywords: Clozapine; Daily dose; Serum concentration; Therapeutic drug monitoring (TDM).

Fig. 1

Relationship between the daily dose of clozapine and serum concentration. The linear regression equation of clozapine daily dose and concentration was Y = 122.793 + 1.065*x, R = 0.513, p < 0.001

Fig. 2

a Relationship between daily dose of clozapine and age groups. With increasing age, the daily dose of clozapine tended to decrease. b1 Relationship between clozapine serum concentrations and age groups. Although there were significant differences in the serum concentrations of clozapine among age groups, there was no significant trend in the daily dose of clozapine with age. b2 Relationship between clozapine serum concentration and age groups.When the subjects were divided into two age groups, 10-44 years old and 45-75 years old, the serum concentration of clozapine was significantly different between the two groups (P <0.01), and the serum concentration of clozapine in the 45-75 years old group was higher than that in the 10-44 years old group. c Relationship between the C/D ratio and age group. With increasing age, the C/D ratio tended to increase. With increasing age, the daily dose of clozapine tended to decrease