Desvenlafaxine

Desvenlafaxine

Clinical data
Pronunciation	/dɛsˌvɛnləˈfæksiːn/ des-ven-lə-FAK-seen
Trade names	Pristiq, Desfax, Ellefore, others
Other names	O-desmethylvenlafaxine, WY-45233
AHFS/Drugs.com	Monograph
MedlinePlus	a608022
License data	US DailyMed: Desvenlafaxine
Pregnancy category	AU: B2
Routes of administration	By mouth
Drug class	Serotonin–norepinephrine reuptake inhibitor (SNRI)
ATC code	N06AX23 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances)[1] CA: ℞-only[2] US: ℞-only
Pharmacokinetic data
Bioavailability	80%
Protein binding	Low (30%)
Metabolism	CYP2C19,[3] CYP3A4, (CYP2D6 is not involved)
Elimination half-life	11 hours
Excretion	45% excreted unchanged in urine
Identifiers
IUPAC name (RS)-4-[2-dimethylamino-1-(1-hydroxycyclohexyl) ethyl]phenol
CAS Number	93413-62-8 Y
PubChem CID	125017
IUPHAR/BPS	7158
DrugBank	DB06700 Y
ChemSpider	111300 Y
UNII	NG99554ANW
KEGG	D07793 Y
ChEBI	CHEBI:83527 N
ChEMBL	ChEMBL1118 Y
CompTox Dashboard (EPA)	DTXSID40869118
ECHA InfoCard	100.149.615
Chemical and physical data
Formula	C16H25NO2
Molar mass	263.381 g·mol−1
3D model (JSmol)	Interactive image
SMILES OC2(C(c1ccc(O)cc1)CN(C)C)CCCCC2
InChI InChI=1S/C16H25NO2/c1-17(2)12-15(13-6-8-14(18)9-7-13)16(19)10-4-3-5-11-16/h6-9,15,18-19H,3-5,10-12H2,1-2H3 Y Key:KYYIDSXMWOZKMP-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Desvenlafaxine, sold under the brand name Pristiq among others, is a medication used to treat depression.^[4] It is an antidepressant of the serotonin–norepinephrine reuptake inhibitor (SNRI) class and is taken by mouth.^[4] It is recommended that the need for further treatment be occasionally reassessed.^[4] Studies have shown similar effectiveness compared to its parent compound venlafaxine.^[5][6]

Common side effects include dizziness, trouble sleeping, increased sweating, constipation, sleepiness, anxiety, and sexual problems.^[4] In some patients, sexual dysfunction may persist even after the drug is discontinued, a condition known as post-SSRI sexual dysfunction; regulatory agencies including the European Medicines Agency and Health Canada have recommended that desvenlafaxine's product labeling warn of this risk.^[7][8] Serious side effects may include suicide in those under the age of 25, serotonin syndrome, bleeding, mania, and high blood pressure.^[4]

Desvenlafaxine was approved for medical use in the United States in 2008.^[4] In Europe its application for use was denied in 2009, although has since been approved for Spain and Germany.^[9] In 2023, it was the 189th most commonly prescribed medication in the United States, with more than 2 million prescriptions.^[10][11]

Desvenlafaxine is primarily used as a treatment for major depressive disorder.^[12] Use has only been studied up to 8 weeks.^[4] Multiple studies have shown comparable effectiveness to venlafaxine as well as a lower rate of nausea.^[5][6] Other studies have shown it to be either less effective^[9] or more effective^[13] than venlafaxine.

Doses of 50 to 400 mg/day appear effective for major depressive disorder, although no additional benefit was demonstrated at doses greater than 50 mg/day, and adverse events and discontinuations were more frequent at higher doses.^[14]

Desvenlafaxine improves the HAM-D17 score^[15] and measures of well-being such as the Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5).^[16]

Desvenlafaxine may also be prescribed off label for the treatment of hot flashes.^[17] A review of studies in 2014 found a 55–69% reduction in number of hot flashes.^[18]

Frequency of adverse effects:^[12][19][20]

Very common adverse effects include:

Common adverse effects include:

Uncommon adverse effects include:

Rare adverse effects include:

Common adverse effects whose intensity is unknown include:

Post-SSRI sexual dysfunction (PSSD) is an iatrogenic condition in which sexual side effects persist after discontinuation of serotonin reuptake inhibiting antidepressants, including desvenlafaxine.^[21][7] Characteristic symptoms include genital numbness, pleasureless or weak orgasm, loss of libido, and erectile dysfunction; non-sexual symptoms such as emotional blunting and cognitive impairment may also occur.^[7] The condition can arise after even brief exposure to a serotonin reuptake inhibitor and may persist indefinitely; there is currently no established treatment.^[22] The DSM-5 noted in 2013 that serotonin reuptake inhibitor-induced sexual dysfunction may persist after the agent is discontinued.^[23]

As the primary active metabolite of venlafaxine, desvenlafaxine shares its parent compound's serotonin reuptake inhibiting mechanism, and PSSD has been reported with both drugs.^[7] A 2023 retrospective cohort study of over 12,000 males estimated the risk of irreversible sexual dysfunction at approximately 0.46% of patients treated with serotonergic antidepressants, including SNRIs, though the actual prevalence remains uncertain and the condition is likely underreported.^[24]

In 2019, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommended that product labels for all SSRIs and SNRIs, including desvenlafaxine, be updated to state that sexual dysfunction may be long-lasting even after treatment is stopped.^[8] Health Canada followed with similar label updates in 2021.^[23] In 2024, Australia's Therapeutic Goods Administration aligned all SSRI and SNRI product information to reflect this risk, noting that desvenlafaxine already carried a warning about persistent sexual dysfunction prior to the alignment.^[25]

Desvenlafaxine is a synthetic form of the isolated major active metabolite of venlafaxine, and is categorized as a serotonin–norepinephrine reuptake inhibitor (SNRI). When most normal metabolizers take venlafaxine, approximately 70% of the dose is metabolized into desvenlafaxine, so the effects of the two drugs are expected to be very similar.^[26] It works by blocking the "reuptake" transporters for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin (5-hydroxytryptamine) and norepinephrine (noradrenaline). It is approximately 10 times more potent at inhibiting serotonin uptake than norepinephrine uptake.^[27]

Wyeth announced on 23 January 2007 that it received an approvable letter from the Food and Drug Administration for desvenlafaxine. Final approval to sell the drug was contingent on a number of things, including:

• A satisfactory FDA inspection of Wyeth's Guayama, Puerto Rico facility, where the drug is to be manufactured;
• Several postmarketing surveillance commitments, and follow-up studies on low-dose use, relapse, and use in children;
• Clarity by Wyeth around the company's product education plan for physicians and patients;
• Approval of desvenlafaxine's proprietary name, Pristiq.^[29]

The FDA approved the drug for antidepressant use in February 2008, and was to be available in US pharmacies in May 2008.^[30]

In March 2017, the generic form of the drug was made available in the US.

On February 4, 2009, Health Canada approved use of desvenlafaxine for treatment of depression.^[31][32]

In 2009, an application to market desvenlafaxine for major depressive disorder in the European Union was declined.^[9] In 2012, Pfizer received authorization in Spain to market desvenlafaxine for the disorder.^[33][34] In August 2022, following a 14-year approval process, desvenlafaxine was brought to the market for the disorder in Germany.^[35] Desvenlaflaxine has been available in Italy since 2022.

Desvenlafaxine is classified as a schedule 4 (prescription only) drug in Australia. It was listed on the Pharmaceutical Benefits Scheme in 2008 for the treatment of major depressive disorders.^[36]

• List of antidepressants