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Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

Abstract Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics. The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model. Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.