Factors predicting serum clozapine levels in Middle Eastern patients: an observational study

Abstract

Background: Despite its superiority over other drugs for psychosis, clozapine remains underused and is associated with many clinical challenges, including difficulties in predicting therapeutic serum levels (350-600 ng/mL). We found no large or recent study that investigated the determinants of serum clozapine levels in Middle Eastern patients. Therefore, we investigated the association between clozapine dose and serum level, and the clinical predictors of the clozapine serum level, in Middle Eastern patients.

Methods: This cross-sectional study included 94 patients of Middle Eastern ethnicity who attended the Clozapine Clinic in King Saud University Medical City in Riyadh, Saudi Arabia. We used a single measure of the serum clozapine level, which was collected 12 h after the last oral dose of clozapine under steady-state conditions.

Results: The average clozapine dose and serum level were 400 mg/daily and 705 ng/mL, respectively. The majority of patients (59.8%) had serum levels higher than 600 ng/mL. Clozapine dose and serum level were positively correlated (r_s [94] = 0.32, p = 0.002). We generated a predictive model of the serum clozapine level, which revealed that the daily dose, smoking status, use of fluvoxamine or lamotrigine, and body mass index (BMI) predicted 43.6% of the variance in the serum level (p < 0.001). Using this model, we calculated that patients with a BMI of 25 kg/m² would require a clozapine dose between 50 to 275 mg/daily if they were non-smokers, and a dose of 200 to 450 mg/daily if they were smokers, in order to reach a serum clozapine level between 350 to 600 ng/mL. Patients with higher BMI and those receiving fluvoxamine would require lower doses.

Conclusions: This was a naturalistic study of the clozapine dose-level relationship and the clinical predictors of the serum clozapine level in a sample of Middle Eastern patients. The ratios of clozapine level to dose in our patients more closely resembled those reported in Asian samples than in European samples. These findings do not reduce the value of individualised therapeutic drug monitoring, but may assist clinicians when prescribing clozapine to Middle Eastern patients. Further psychopharmacological studies are needed on this demographic population.

Keywords: Clozapine; Middle East; Psychosis; Schizophrenia; Serum.