Comparing Venlafaxine Versus Desvenlafaxine

In comparing (Effexor) venlafaxine versus desvenlafaxine (Pristiq), you can’t help but start with pharmacokinetics. As you gander at the names of the drugs, it’s hard not to notice that they are nearly identical minus a few letters. Let’s break this down as well as several other considerations when choosing which medication to use.

Venlafaxine Versus Desvenlafaxine – Kinetics

Venlafaxine is a prodrug and metabolized to desmethylvenlafaxine. CYP2D6 is the primary enzyme responsible for the conversion of venlafaxine to its active metabolite. This means that CYP2D6 inhibitors could slow down this effect and reduce the effectiveness of venlafaxine compared to desvenlafaxine. In addition, pharmacogenomic variations could also impact the efficacy or risk for adverse drug reactions. Rapid metabolizers of venlafaxine could lead to higher concentrations of the active metabolite while slow metabolizers would likely have a reduced response. Desvenlfaxine is an active medication and does not require activation.

Why Does Anyone Use Venlafaxine?

After reading the ins and outs of venlafaxine activation, you might question why anyone would use venlafaxine? Venlafaxine has been around for a much longer time than desvenlafaxine and is less expensive. That’s the simple answer. In addition to the cost, venlafaxine has been better studied in multiple disease states (depression, migraine, anxiety, PTSD, etc.). Desvenlafaxine has very limited studies, other than depression. Prescriber comfort and experience also play a role.

Renal Elimination

While both drugs have some dependence on renal function for elimination, desvenlafaxine is significantly eliminated in the urine as unchanged drug. It is nearly 50% eliminated unchanged in the urine. Healthcare professionals should recognize that the risk for adverse effects goes up as a patient’s renal function declines.

Dosing and Dosage Forms

Venlafaxine has an immediate release and extended-release formulation. In practice, I have seen numerous errors with venlafaxine due to the different dosage forms. The immediate-release product is typically dosed twice daily while the extended-release product is usually dosed once daily. When comparing venlafaxine versus desvenlafaxine in this respect, I’d give the edge to desvenlafaxine due to its simplicity. Desvenlafaxine only has one dosage form and is typically dosed once daily.

Are there any other differences of venlafaxine versus desvenlafaxine that matter in your practice?

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Written By Eric Christianson

July 27, 2022

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