Key differences between Venlafaxine XR and Desvenlafaxine: An analysis of pharmacokinetic and clinical data

Venlafaxine XR and its major active metabolite, desvenlafaxine, are serotonin-norepinephrine reuptake inhibitors. Both are FDA-approved for the treatment of major depressive disorder and have essentially the same pharmacologic and pharmacokinetic profiles; however, the recommended dosing is notably different. The FDA approved recommended starting and maintenance dose for desvenlafaxine is 50 mg daily, while venlafaxine XR requires titration from 37.5 mg daily to the maintenance dose of 150 - 225 mg daily. The dose recommendation for desvenlafaxine is based on results from 8-week acute-phase clinical trials, but complete therapeutic response is not always achieved in this short time period. Venlafaxine XR relies on CYP2D6 for conversion to desvenlafaxine while desvenlafaxine has no significant metabolism by CYP2D6 at recommended doses. Both venlafaxine XR and desvenlafaxine have limited clinically significant drug interactions. The most striking difference between the two products is cost.