Conducting Therapeutic Drug Monitoring of Venlafaxine in the Context of Individualization of Pharmacotherapy for Depression

Background: therapeutic drug monitoring represents one of the most promising tools in clinical practice to optimise antidepressant treatment. Nevertheless, little is still known regarding the relationship between clinical efficacy and serum/ plasma concentration of venlafaxine. The aim of study was to develop personalized approaches to prescribing venlafaxine for depression through therapeutic drug monitoring of minimum and maximum levels of the drug. Patients, Materials and Methods: 52 hospitalized patients with depression (F32 and F33 according to ICD-10) receiving venlafaxine were selected. Plasma concentrations of the drug and its active metabolite O-desmethylvenlafaxine were determined using a validated HPLC-MS method. The effects of potentially infiuencing factors was assessed using a multivariate linear regression model. Results: 73% and 67% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range (previous and revised therapeutic ranges respectively). Plasma concentrations were dependent on age, weight, and CYP2D6 activity. Venlafaxine metabolism expressed as a metabolite-to-parent concentrations ratio was infiuenced by a combination of age, CYP2D6, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and two per day administration. Combining variables made an additive effect on plasma concentrations. Active moiety plasma concentrations were higher in older women. Conclusion: this study strongly suggests that monitoring could represent a more appropriate tool than the oral dosage to optimise the treatment with venlafaxine. Specifically, highest efficacy might be achieved in patients at active moiety levels around 400 ng/mL. Therapeutic drug monitoring of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.

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