Impact of Body Mass Index on Serum Concentrations of Antidepressants and Antipsychotics

Background: Rates of overweight and obesity are higher in patients suffering from psychiatric disorders than in the general population. Body composition and enzyme functions are affected by overweight, and consequently, the pharmacokinetics of drugs may vary in overweight patients. Thus, overweight and obesity are important factors in psychiatric disorders and their treatment. This analysis aimed to investigate the impact of body mass index (BMI) on serum concentrations of the antidepressant drugs amitriptyline, doxepin, escitalopram, mirtazapine, and venlafaxine, and the antipsychotic drugs clozapine, quetiapine, and risperidone, taking into account the following confounding parameters: age, sex, and smoking habit. Methods: Inpatients and outpatients (N = 1657) who took at least one of the target drugs were included in this retrospective analysis. Serum concentrations of the target drugs and their metabolites were determined at the Department of Psychiatry, Psychosomatics, and Psychotherapy of the University Hospital of Wurzburg during routine therapeutic drug monitoring (January 2009-December 2010), which was performed in the morning (trough level) at steady state. Results: Dose-corrected serum concentrations (CD) of the active moiety of doxepin and venlafaxine and of O-desmethylvenlafaxine were negatively associated with BMI (partial Pearson correlation, R = -0.267, P = 0.002; R = -0.206, P <= 0.001; R = -0.258, P <= 0.001), and the CDs were different in normal weight, overweight, and obese patients (analysis of covariance, P = 0.004, P < 0.001, P <= 0.001). No association was found between BMI and serum concentrations of amitriptyline, escitalopram, mirtazapine, clozapine, quetiapine, and risperidone. Conclusions: In obese patients, higher doses of doxepin and venlafaxine are necessary to achieve similar serum concentrations as in normal weight patients and to avoid treatment-resistant depression.