Additive effects of sex, age and smoking on serum levels of venlafaxine and O-desmethylvenlafaxine under naturalistic conditions

Introduction: Venlafaxine (VEN) is a modern antidepressant which exerts both serotonin and norepinephrine reuptake inhibition. In this study we examined the influence of sex, age and smoking on serum concentrations of VEN, its metabolite O-desmethylvenlafaxine (ODVEN) and the sum of both (SUM) in patients treated with VEN under naturalistic conditions. Methods: We retrospectively evaluated therapeutic drug monitoring (TDM) analyses of VEN in 234 patients treated in the psychiatric university hospitals of Mainz, Regensburg, and Würzburg for a depressive episode (ICD-10 F3x). The determination of serum concentrations was performed by virtually identical chromatographic methods in the therapeutic drug monitoring (TDM) laboratories of the participating hospitals. Results: Serum concentrations varied widely depending on the variables sex, age and smoking. Although there was no significant difference between the 8 groups (smokers vs. non-smokers x males vs. females x ≤ 60 years vs. > 60 years) regarding daily dose and venlafaxine serum concentration, smoking males ≤ 60 years (n = 15) had a mean serum concentration of ODVEN and SUM of 150.40 ng/ml (SD 77.86) and 251.00 ng/ml (SD 106.65), which is less than half of serum concentrations of non-smoking females > 60 years (n = 26, ODVEN mean 309.08 ng/ml, SD 195.11 and SUM mean 508.04 ng/ml, SD 268.03). An ANOVA over the 8 different groups is significant for ODVEN (p < 0.028) and SUM (p < 0.011). Discussion: Variables like sex, age and smoking should be considered for optimal dosing of patients with VEN. There seems to be an additive effect of these variables regarding their influence on the serum concentrations of VEN that can lead to a greater risk of under- or overdosage of VEN.