Review of Duloxetine and Venlafaxine in Depression

Objectives: To compare the efficacy and pharmacologic, pharmacokinetic, drug interaction and adverse effect profiles of duloxetine and venlafaxine. Methods: A systematic review of the literature pertaining to duloxetine and venlafaxine was conducted using a computer-aided search of MEDLINE and EMBASE for the period January 1988 to May 2008 with the following search terms: venlafaxine and duloxetine and depression, clinical studies, pharmacology, drug interactions, pharmacokinetics, adverse effects, safety, case reports and review articles. Results: Duloxetine and venlafaxine have comparable efficacy and share similar pharmacologic profiles but differ somewhat in their pharmacokinetic profiles, drug interactions and adverse effects. Both agents block the reuptake of serotonin and norepinephrine and both are substrates for the cytochrome P450 2D6 isoenzyme; however, duloxetine inhibits these enzymes to a moderate extent, whereas venlafaxine is only a weak inhibitor. Furthermore, duloxetine is more extensively bound to protein than venlafaxine. Venlafaxine is more likely to elevate blood pressure in a dose-related manner. Both duloxetine and venlafaxine have the potential to cause hepatic injury. Conclusions: Although venlafaxine and duloxetine have similar efficacy in the treatment of depression, differences in their adverse effects and pharmacokinetic profiles suggest that one agent may be preferred over the other in certain patient groups.