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 serum levels. We found no large or recent study that investigated the determinants of serum clozapine levels in Middle Eastern patients. We thus investigated the association between clozapine dose and serum levels and the clinical predictors of clozapine serum levels in Middle Eastern patients.Methods: This was a cross-sectional study including 94 patients of Middle Eastern ethnicity attending the Clozapine Clinic in King Saud University Medical City in Riyadh, Saudi Arabia.Results: The average clozapine dose and serum level were 400 mg/daily and 705 ng/mL, respectively. Clozapine dose and serum levels were positively correlated (rs [94]=0.32, p=0.002). We generated a predictive model of serum clozapine levels 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 serum levels (p<0.001). Using this model, we calculated that the maximum doses of clozapine to avoid levels above the optimal range (>650 ng/mL) were 300, 250, or 225 mg/day for non-smokers with a body mass index of 25, 30, or 35 kg/m2, respectively, and 475, 425, or 400 mg/day for smokers with a body mass index of 25, 30, or 35 kg/m2, respectively.Conclusions: This is a naturalistic study of the clozapine dose-level relationship and the clinical predictors of serum clozapine levels in Middle Eastern patients. 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.