Desvenlafaxine

The exact mechanism of the antidepressant action of desvenlafaxine is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non-clinical studies have shown that desvenlafaxine is a potent and selective SNRI.

• PRISTIQ is indicated for the treatment of adults with major depressive disorder (MDD) [see Clinical Studies (14) ] . PRISTIQ is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of adults with major depressive disorder (MDD) ( 1 ).ICD-10: F32.9

• • Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the PRISTIQ formulation. Angioedema has been reported in patients treated with PRISTIQ [see Adverse Reactions (6.1) ] .contraindicated

• Recommended dose: 50 mg once daily with or without food ( 2.1 ). • There was no evidence that doses greater than 50 mg per day confer any additional benefit ( 2.1 ). • The 25 mg per day dose is intended for a gradual reduction in dose when discontinuing treatment or dosing in severe renal and end-stage renal disease patients ( 2.1 ). • Discontinuation: Reduce dose gradually whenever possible ( 2.1 ). • Take tablets whole; do not divide, crush, chew, or dissolve ( 2.1 ). • Moderate renal impairment: Maximum dose 50 mg per day ( 2.2 ). • Severe renal impairment and end-stage renal disease: Maximum dose 25 mg per day or 50 mg every other day ( 2.2 ). • Moderate to severe hepatic impairment: Maximum dose 100 mg per day ( 2.3 ). 2.1 General Instructions for Use The recommended dose for PRISTIQ is 50 mg once daily, with or without food. The 50 mg dose is both a starting dose and the therapeutic dose. PRISTIQ should be taken at approximately the same time each day. Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved. In clinical studies, doses of 10 mg to 400 mg per day were studied. In clinical studies, doses of 50 mg to 400 mg per day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg per day and adverse reactions and discontinuations were more frequent at higher doses. The 25 mg per day dose is intended for a gradual reduction in dose when discontinuing treatment.

• Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue PRISTIQ and serotonergic agents and initiate supportive treatment ( 5.2 ). • Elevated Blood Pressure: Control hypertension before initiating treatment. Monitor blood pressure regularly during treatment ( 5.3 ). • Increased Risk of Bleeding: Concomitant use of aspirin, NSAIDs, other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.4 ). • Angle Closure Glaucoma: Avoid use of antidepressants, including PRISTIQ, in patients with untreated anatomically narrow angles treated ( 5.5 ). • Activation of Mania/Hypomania: Use cautiously in patients with Bipolar Disorder. Caution patients about risk of activation of mania/hypomania ( 5.6 ). • Discontinuation Syndrome: Taper dose when possible and monitor for discontinuation symptoms ( 5.7 ). • Seizure: Can occur. Use cautiously in patients with seizure disorder ( 5.8 ). • Hyponatremia: Can occur in association with SIADH ( 5.9 ). • Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur ( 5.10 ). • Sexual Dysfunction: PRISTIQ may cause symptoms of sexual dysfunction ( 5.11 ). 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients Patients with MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.

The following adverse reactions are discussed in greater detail in other sections of the label. • Hypersensitivity [see Contraindications (4) ] • Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients [see Warnings and Precautions (5.1) ] • Serotonin Syndrome [see Warnings and Precautions (5.2) ] • Elevated Blood Pressure [see Warnings and Precautions (5.3) ] • Increased Risk of Bleeding [see Warnings and Precautions (5.4) ] • Angle Closure Glaucoma [see Warnings and Precautions (5.5) ] • Activation of Mania/Hypomania [see Warnings and Precautions (5.6) ] • Discontinuation Syndrome [see Warnings and Precautions (5.7) ] • Seizure [see Warnings and Precautions (5.8) ] • Hyponatremia [see Warnings and Precautions (5.9) ] • Interstitial Lung Disease and Eosinophilic Pneumonia [see Warnings and Precautions (5.10) ] • Sexual Dysfunction [see Warnings and Precautions (5.11) ] Most common adverse reactions (incidence ≥5% and twice the rate of placebo in the 50 or 100 mg dose groups) were: nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and specific male sexual function disorders ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

• Pregnancy: Third trimester use may result in neonatal discontinuation syndrome ( 8.1 ). • Geriatric Use : There is an increased incidence of orthostatic hypotension in desvenlafaxine treated patients ≥ 65 years ( 6.1 and 8.5 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants . Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.4) and Clinical Considerations ] . There are no published studies on PRISTIQ in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes (see Data ) . There are risks associated with untreated depression in pregnancy and with exposure to SNRIs and SSRIs, including PRISTIQ, during pregnancy ( see Clinical Considerations ).

Metabolism

The single-dose pharmacokinetics of desvenlafaxine are linear and dose-proportional in a dose range of 50 to 600 mg (1 to 12 times the recommended approved dosage) per day. With once-daily dosing, steady-state plasma concentrations are achieved within approximately 4 to 5 days.

10.1 Human Experience with Overdosage There is limited clinical trial experience with desvenlafaxine succinate overdosage in humans. However, desvenlafaxine (PRISTIQ) is the major active metabolite of venlafaxine. Overdose experience reported with venlafaxine (the parent drug of PRISTIQ) is presented below; the identical information can be found in the Overdosage section of the venlafaxine package insert. In postmarketing experience, overdose with venlafaxine (the parent drug of PRISTIQ) has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), sinus and ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported.

• Feb 29, 2008NDANDA021992Pf Prism Cv
• Mar 4, 2013NDANDA204150Alembic Pharms Ltd
• Jun 29, 2015ANDAANDA204003Alembic
• Jun 29, 2015ANDAANDA204028Rubicon Research
• Jun 29, 2015ANDAANDA204172Lupin
• Feb 16, 2016ANDAANDA204083Hikma
• Jul 29, 2016ANDAANDA204065Actavis Labs Fl
• Oct 1, 2018ANDAANDA210014Yichang Humanwell

1. 1Drug Ineffective2,68910%
2. 2Nausea2,4079.1%
3. 3Headache1,9217.2%
4. 4Dizziness1,8887.1%
5. 5Anxiety1,7986.8%
6. 6Fatigue1,6596.3%
7. 7Insomnia1,5625.9%
8. 8Feeling Abnormal1,4485.5%
9. 9Depression1,3685.2%
10. 10Drug Withdrawal Syndrome1,0514.0%
11. 11Malaise1,0373.9%
12. 12Off Label Use1,0363.9%
13. 13Diarrhoea9393.5%
14. 14Condition Aggravated9323.5%
15. 15Pain9003.4%

Recent PubMed references pinned to Desvenlafaxine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Efficacy and Safety of Desvenlafaxine for the Treatment of Persistent Idiopathic Dentoalveolar Pain: A Retrospective Observational Study.
  Pain research & management · 2026 · Liu M, Ren H, Zhao C, et al.
  PMID 42144840DOI 10.1155/prm/8835808
• Separating O-desmethylvenlafaxine and tramadol enantiomers using two-dimensional chiral LC × DMS mass spectrometry.
  The Analyst · 2026 · McLachlan AD, Vakharia R, Nazdrajić E, et al.
  PMID 41810740DOI 10.1039/d6an00119j
• New co-drugs of O-demethylvenlafaxine and NSAIDs exert antidepressant effects by alleviating inflammation, oxidative stress, and increasing neurotransmitter.
  International immunopharmacology · 2026 · Song Y, Song J, Liu S, et al.
  PMID 41785603DOI 10.1016/j.intimp.2026.116456
• Identification of antidepressant response-related changes to DNA methylation and gene expression.
  The international journal of neuropsychopharmacology · 2026 · Fiori LM, Nagy C, Turecki G, et al.
  PMID 41593764DOI 10.1093/ijnp/pyag001
• Efficacy and safety of Toludesvenlafaxine extended-release tablets in the treatment of treatment-resistant depression.
  BMC psychiatry · 2025 · Qi Z, Xiaowen G, Wenjie L, et al.
  PMID 41257691DOI 10.1186/s12888-025-07584-8
• Analysis of reward behavior in patients with MDD and partial response to SSRI therapy treated with vortioxetine versus desvenlafaxine: Experience with the Effort-Expenditure for Rewards Task (EEfRT) in the VIVRE study.
  Journal of affective disorders · 2025 · Gill H, McIntyre RS, Christensen MC, et al.
  PMID 40456468DOI 10.1016/j.jad.2025.119563
• Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-Release Tablets in Depression With Anhedonia: A Single-Arm, Multicenter Clinical Study.
  Depression and anxiety · 2025 · Wang SW, Mi WF, Hao XN, et al.
  PMID 40365616DOI 10.1155/da/6130764
• Advancing inclusive healthcare through PBPK modelling: predicting the impact of CYP genotypes and enzyme ontogenies on infant exposures of venlafaxine and its active metabolite O-desmethylvenlafaxine in lactation.
  Journal of pharmacokinetics and pharmacodynamics · 2025 · Pan X, Rowland Yeo K
  PMID 40185984DOI 10.1007/s10928-025-09969-4

The 10 most recently updated of 98 ClinicalTrials.gov registrations naming Desvenlafaxine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study Following Women in Menopause Treated With a Non-hormonal Therapy for Hot Flashes and Night Sweats
  Completed · Observational · 999 enrolled · Astellas Pharma Global Development, Inc.
  NCT06049797updated 2026-06-05
• Predictors of Cognitive Outcomes in Geriatric Depression
  Active not recruiting · Phase 4 · Interventional · 75 enrolled · David Steffens
  NCT05273996updated 2026-05-22
• Desvenlafaxine for Preventive Treatment of Frequent Migraines
  Active not recruiting · Interventional · 440 enrolled · Tongji Hospital
  NCT07385755updated 2026-02-04
• The Analgesic Efficacy and Safety of Desvenlafaxine in Patients With Herpes Zoster
  Recruiting · Interventional · 750 enrolled · Beijing Tiantan Hospital
  NCT07361809updated 2026-01-23
• Desvenlafaxine for Preventive Treatment of Frequent Episodic Tension-type Headache
  Active not recruiting · Interventional · 432 enrolled · Tongji Hospital
  NCT07359248updated 2026-01-22
• The Efficacy and Safety of Pregabalin Combined With Desvenlafaxine in Patients With Fibromyalgia
  Recruiting · Interventional · 384 enrolled · Beijing Tiantan Hospital
  NCT07171320updated 2025-11-17
• Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression
  Not yet recruiting · Phase 2 · Interventional · 80 enrolled · University of Illinois at Chicago
  NCT06591091updated 2025-09-04
• Implementation of Personalized Medicine for Optimal Drug Therapy in Cancer
  Recruiting · Observational · 600 enrolled · London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
  NCT05830279updated 2025-07-09
• A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
  Completed · Phase 2 · Interventional · 107 enrolled · Janssen Research & Development, LLC
  NCT03321526updated 2025-04-29
• Non-interventional, Retrospective Cohort Study to Explore Antidepressant Treatment in Korea
  Completed · Observational · 370,212 enrolled · Pfizer
  NCT04446039updated 2024-12-09

CPIC-curated drug–gene pairs for Desvenlafaxine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• HTR2ACPIC C
  CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants
• SLC6A4CPIC C
  CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants

Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

• VenlafaxineSerotonin and Norepinephrine Reuptake Inhibitor97%

Frequently asked questions

How does Desvenlafaxine work?

The exact mechanism of the antidepressant action of desvenlafaxine is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non-clinical studies have shown that desvenlafaxine is a potent and selective SNRI.

What is Desvenlafaxine used for?

According to FDA labeling, Desvenlafaxine carries indications including: PRISTIQ is indicated for the treatment of adults with major depressive disorder (MDD) [see Clinical Studies (14) ] . PRISTIQ is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of adults with major depressive disorder (MDD) ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Desvenlafaxine?

Desvenlafaxine is classified as Other antidepressants, Serotonin and Norepinephrine Reuptake Inhibitor, Cytochrome P450 2D6 Inhibitors, Monoamine Oxidase Inhibitors, Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors, Increased Central Nervous System Norepinephrine Activity, Increased Central Nervous System Serotonin Activity.

What are the brand names for Desvenlafaxine?

Desvenlafaxine is marketed under brand names including Khedezla, Pristiq.

What are the contraindications for Desvenlafaxine?

Desvenlafaxine labeling lists contraindications including: • Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the PRISTIQ formulation. Angioedema has been reported in patients treated with PRISTIQ [see Adverse Reactions (6.1) ] .. Always consult the full prescribing information and a clinician.