Relationship between Blood Levels and Clinical Efficacy of Two Different Formulations of Venlafaxine in Female Patients with Depression

Background: Different formulations of the same medication can have distinct dissociation profiles and release rates resulting in different onset times and durations of action; these differences may influence the clinical efficacy and adverse reactions of the medication.Objective: Assess the relationship between the plasma concentrations and the clinical efficacy and adverse reaction profile of two formulations of venlafaxine (VL) in female patients with major depression.Methods: Sixty female patients hospitalized for depression were randomly assigned to use EFFEXOR XR®, the extendedrelease formulation of venlafaxine (hereafter, the XR group), or Bolexin®, the immediate-release formulation of venlafaxine (hereafter, the IR Group), for six weeks. The mean (SD) total daily dose in the XR group was 168 (32) mg/d administered in one oral dose in the morning and that in the IR group was 160 (67) mg/day administered in three oral doses over the day. At the end of the first, second, fourth and sixth week of treatment the plasma concentrations of VL and its active metabolite, O-desmethylvenlafaxine (ODV), were determined using high-performance liquid chromatography and the clinical efficacy and adverse reactions were accessed using the Hamilton Depression Rating Scale (HAMD) and the Treatment Emergent Symptoms Scale (TESS). A reduction in the baseline HAMD score of 50% or greater was deemed remission.Results: No serious adverse reactions were observed. There were no significant differences in the mean HAMD scores between the two groups at any of the time points evaluated. Mean HAMD scores after six weeks of treatment were significantly lower in both treatment groups; the overall remission rate was 65.6% in the XR group and 69.2% in the IR group (χ2=0.77, p=0.380). Changes in the HAMD scores from baseline were only weakly correlated with changes in the plasma concentrations of ODV (rs=-0.10, p=0.470) and VL (rs=-0.11, p=0.403).Conclusion: Both the extended-release and immediate-release formulations of VL were efficacious and well tolerated in female patients with depression. Plasma concentrations of VL and ODV are not closely related to clinical efficacy so they are not suitable as markers for the clinical effectiveness of treatment with venlafaxine.