[Therapeutic drug monitoring of antidepressants: Why venlafaxine is the most monitored drug? A review of literature]

Abstract

Venlafaxine is the third most frequently prescribed antidepressant in France the last decade, with about 400,000 daily doses. Therapeutic drug monitoring (TDM) of this medication, by measuring the active moiety venlafaxine (V) and O-desmethylvenlafaxine (ODV), is recommended (level of recommendation 2). However, this antidepressant seems to be the one for which clinicians most often use TDM, much more frequently than escitalopram, which is more prescribed and for which TDM is also recommended. The main goal of this review is to provide an update on the TDM of venlafaxine: its therapeutic interval, its level of recommendation and the origin of its "success". From the literature does not enable to define a therapeutic interval for the active moiety V+ODV, that is to say a steady-state trough concentration allowing a clinical response without toxicity. Nevertheless, a target concentration from 100 to 400μg/L is certainly relevant for the majority of patients without any pharmacodynamic resistance ; though a greater concentration could result in an earlier response or could be required for a clinical response in a minority of patients. A patient with no clinical response despite a concentration greater than 1000μg/L should be proposed another antidepressant. Measurement of the ODV/V ratio is also a useful tool, values below 0.3 usually reflecting a slow metabolizer phenotype for cytochrome P-450 2D6, which is more at risk of adverse effects. Research for this phenotype probably explains many prescriptions for TDM.

Keywords: Antidepressive agents; Antidépresseurs; CYP2D6; Cytochrome P-450 CYP2D6; Drug monitoring; Suivi thérapeutique pharmacologique; Venlafaxine hydrochloride.