Ethnic Differences in Dose and Levels of Clozapine: Exploring Need for Any Specific Monitoring Needs

AIMS: Clinical research shows that compared to Caucasian patients, Asian patients appear to have a lower clozapine dose requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy. Secondly, studies in the UK report that Asian patients with treatment-resistant schizophrenia were less likely to receive clozapine than Caucasian patients. The objectives of this study were to find out the ethnic difference in dose and levels of clozapine in ethnic minority patient (BME (Black and minority ethnic) populations and to explore if there is a need for any specific monitoring. METHODS: Demographic (age, gender, and ethnicity) and clinical variables (diagnosis, clozapine dose, plasma level of clozapine and nor-clozapine, smoking status, side effect profile, and physical comorbidities) were collected from the electronic patient records and analysed. RESULTS: The sample consisted of 66 (56.4%) Caucasians, 22 (18.8%) Asians, 21 (17.9%) African-Caribbean, and 8 (6.8%) mixed ethnicity patients. Their age range was 19-80, with an average of 46.9 ±11.9 years. Among the ethnic groups, age, clozapine, nor-clozapine level and QTc were comparable, except for the dose of clozapine; Caucasian had the highest dose (414.8±140.0 mg), followed by African-Caribbean (373.8±163.7 mg), Asian (333.8±121.2 mg) and mixed (260.7±110.7 mg) (F3.68, p<0.05). The difference remained significant when all the BME groups were combined as well. Side effects such as hypersalivation, drowsiness, blurred vision, polyuria, sore throat, headache, vomiting (none), dizziness, difficulty passing urine, urine incontinence, flu-like symptoms, nausea, were comparable among ethnic groups. There was no difference in smoking among the groups. Considering comorbidities compared to BME, Caucasians had significantly lower rate of hypertension (27.1% vs 9.1%, p<0.01); diabetes (18.6% vs 4.5%, p<0.05), however dyslipidemia (5.1% vs 3.0%) was comparable. In addition to the above, the dose of clozapine was positively correlated with clozapine and norclozapine levels (p<0.05). Clozapine and norclozapine levels correlated significantly (p<0.001). Age was negatively correlated with norclozapine assay (p<0.05) and positively with the number of cigarettes. It appears as the age increases, the number of cigarettes goes up, and norclozapine levels come down. CONCLUSION: There are a few variations of clozapine prescribing in different ethnic groups. Although the Caucasians had higher doses, they had comparable blood levels. A higher proportion of BME patients on clozapine had hypertension and diabetes, emphasizing metabolic risk. Our study findings suggest clozapine monitoring should look into ethnicity related risk factors.