Desvenlafaxine (Pristiq®)

Desvenlafaxine in Brief
  • Generic name: Desvenlafaxine succinate
  • Brand names: Pristiq®
  • Therapeutic class: Antidepressant
  • Pharmacologic class: Serotonin and Norepinephrine reuptake inhibitor (SNRI)
  • FDA Approved: February 2008
  • Chemical Formula: C16H25NO2•C4H6O4•H2O
  • Pregnancy Category: C
  • Habit forming? Not known
  • Originally discovered: 2008, Wyeth, USA USA

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD


O-desmethylvenlafaxine, or simply desvenlafaxine, is the primary active metabolite of venlafaxine (a breakdown product). It was introduced in 2008 as desvenlafaxine succinate. Desvenlafaxine was developed in the hope of improving on the strengths of the parent drug.

On February 4, 2009, Health Canada approved use of desvenlafaxine for treatment of depression in Canada.


Key pharmacokinetic data:

  • Bioavailability: 80%
  • Half-life: 11 hours
  • Time to maximum concentration: 7.5 hours
  • Protein binding: 30%
  • Undergoes minimal metabolism via the CYP 450 isoenzymes and 45% of the dose is excreted unchanged in the urine.

FDA approved indications

  • Major depressive disorder (MDD)

Off-label & Investigational uses

  • Hot flashes associated with menopause 3

What is the difference between Effexor and Pristiq?

Desvenlafaxine delivers the main active metabolite of venlafaxine (Effexor) in an already active state without having to pass through the liver. Desvenlafaxine is NOT metabolized by cytochrome P450 (CYP 2D6) enzymes.

Venlafaxine, in contrast to desvenlafaxine, passes through the liver and undergoes extensive metabolism by the hepatic cytochrome P450 (CYP 2D6) enzymes to become O-desmethylvenlafaxine.

As a result, desvenlafaxine has a lower risk of drug interactions compared to venlafaxine.

Additionally, venlafaxine and desvenlafaxine differ in their relative degree of serotonin and norepinephrine reuptake inhibition. Desvenlafaxine's affinity for serotonin receptors is less than venlafaxine (Ki = 40.2 and 13.5 nmol/L, respectively), while its affinity for norepinephrine is greater than venlafaxine’s (Ki = 558.7 and 1,668.0 nmol/L, respectively) 7.

Is Pristiq better than Effexor?

Basically, using desvenlafaxine rather than venlafaxine skips the step of metabolism through the enzyme systems in the liver. There is no evidence that desvenlafaxine is more effective, safer or better tolerated than venlafaxine 2.

In theory, in persons who have poor functioning CYP2D6 enzymes, Pristiq may be beneficial.

Desvenlafaxine may have an advantage in terms of simpler dosing than venlafaxine (lower starting dose, lower minimum therapeutic dose), with more predictable drug levels.

The bottom line -- there is no any impressive advantage of desvenlafaxine over venlafaxine.


DesVenlafaxine "pros" and "cons"


  • Titrated more quickly, than venlafaxine. In order to maximize tolerance, doctors usually take 7-10 days or longer to uptitrate the dose of venlafaxine to the target of 150-225 mg/day. In contrast, desvenlafaxine is started at the target dose of 50 mg/day from the very first day.
  • Negligibly metabolized in the liver -- minimal impact on cytochrome P450 enzyme system.
  • Low risk of pharmacokinetic drug interactions due to minimal impact on cytochrome P450 enzyme system.
  • Negligibly metabolized in the liver.
  • Low risk of negative effects on sexual functioning 5.
  • May prevent relapse of depression during a 6-month period 8.
  • Desvenlafaxine therapy may improve cognitive functioning (including working memory) in depressed patients9.


  • Currently, there are NO head-to-head trials comparing desvenlafaxine (Pristiq) with other antidepressants (e.g. selective serotonin reuptake inhibitors)
  • Blood pressure elevation10 -- In clinical trials using 50 mg/day the maximum increase in mean systolic and diastolic blood pressure was 3.3 mmHg and 2.1 mmHg, respectively.
  • Increased cholesterol -- may raise cholesterol and triglyceride levels.
  • Lack of an alternative formulation such as a liquid for patients who cannot swallow the ER tablet intact.
  • Expensive!

Mechanism of action

Desvenlafaxine does not have a novel mechanism of action. It is an SNRI that is about 11 times more potent an inhibitor of serotonin (5-HT) reuptake than of norepinephrine (NE) reuptake.

Desvenlafaxine does not have significant affinity for cholinergic, histaminergic, dopaminergic, or α-adrenergic receptors.Time to clear out of the system

DesVenlafaxine has elimination half-life about 11 hours. It may take 2 to 3 days for desvenlafaxine to clear out of the system.

Desvenlafaxine is metabolized primarily via glucuronidation, and to a minor extent through CYP3A4.

Side effects

Side effects with desvenlafaxine are similar to those with venlafaxine:

  • Nausea
  • Insomnia
  • Somnolence
  • Dry mouth
  • Dizziness
  • Sweating
  • Nervousness
  • Anorexia
  • Constipation
  • Fatigue
  • Abnormal ejaculation/orgasm


Discontinuing desvenlafaxine can be problematic for many patients. Abrupt discontinuation may cause dizziness, headache, nausea, irritability, and diarrhea11. A gradual dose reduction with close monitoring is recommended.References

  • 1. U.S. FDA. Pristiq (Venlafaxine) Prescribing Information.
  • 2. Coleman KA, Xavier VY, Palmer TL, Meaney JV, Radalj LM, Canny LM. An indirect comparison of the efficacy and safety of desvenlafaxine and venlafaxine using placebo as the common comparator. CNS Spectr. 2012 Sep;17(3):131-41 PubMed
  • 3. Speroff L, Gass M, Constantine G, Olivier S; Study 315 Investigators. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol. 2008 Jan;111(1):77-87. PubMed
  • 4. European Medicines Agency: Ellefore
  • 5. Clayton AH, Reddy S, Focht K, Musgnung J, Fayyad R. An evaluation of sexual functioning in employed outpatients with major depressive disorder treated with desvenlafaxine 50 mg or placebo. J Sex Med. 2013 Mar;10(3):768-76.
  • 6. Center for Drug Evaluation and Research. Pristiq (Desvenlafaxine Succinate) Extended Release Tablets Application Number: 21–992.
  • 7. National Drug Monograph Desvenlafaxine succinate (Pristiq), September 2010. VA Pharmacy Benefits Management Services.
  • 8. Rosenthal JZ1, Boyer P, Vialet C, Hwang E, Tourian KA. Efficacy and safety of desvenlafaxine 50 mg/d for prevention of relapse in major depressive disorder:a randomized controlled trial. J Clin Psychiatry. 2013 Feb;74(2):158-66. PubMed
  • 9. Reddy S, Fayyad R, Edgar CJ, Guico-Pabia CJ, Wesnes K. The effect of desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder: a substudy of a randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2016 Jun;30(6):559-67. PubMed
  • 10. Thase ME, Fayyad R, Cheng RF, Guico-Pabia CJ, Sporn J, Boucher M, Tourian KA. Effects of desvenlafaxine on blood pressure in patients treated for major depressive disorder: a pooled analysis. Curr Med Res Opin. 2015 Apr;31(4):809-20. PubMed
  • 11. Ninan PT, Musgnung J, Messig M, et al. Incidence and Timing of Taper/Posttherapy-Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder. Prim Care Companion CNS Disord. 2015 Feb 5;17(1). PubMed

Published: June 08, 2013
Last updated: February 01, 2017

Interesting facts

pristiq facts
  • Desvenlafaxine has not been directly compared to available antidepressants in terms of efficacy.
  • In the European Union desvenlafaxine has not been approved.
  • On 2008, Wyeth withdrew its application for Ellefore in Europe because the European Medicines Agency (EMEA) was critical of the evidence, particularly the lack of statistically significant results in several trials4.
  • Many experts say the new Pristiq was a way to get patients on to a branded product... before Effexor XR went generic.

More Facts
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