Desvenlafaxine (Pristiq) Patient Guide: Benefits, Dosing, and Side Effects Explained

This guide is adapted from the clinician guide authored by Sebastián Malleza, M.D., M.Sc. at the Psychopharmacology Institute. For the complete clinical resource, visit: Desvenlafaxine Guide: Pharmacology, Indications, Dosing Guidelines and Adverse Effects

What is Desvenlafaxine?

Desvenlafaxine (brand name Pristiq) is a medication used to treat major depressive disorder (MDD). It belongs to a group of medications called SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors)[1,2]. Desvenlafaxine is actually the active metabolite of another antidepressant called venlafaxine (Effexor), which means it’s the substance venlafaxine naturally converts to in your body[3].

How Does This Medication Work?

Desvenlafaxine works by increasing the levels of two important brain chemicals called serotonin and norepinephrine[1,2]. These chemicals help regulate your mood, energy levels, and other functions in your body.

At lower doses, desvenlafaxine primarily affects serotonin. As the dose increases, it also begins to affect norepinephrine more strongly[4]. This dual action may help improve both mood symptoms and physical symptoms of depression like fatigue and lack of energy[5].

How to Take This Medication

Desvenlafaxine comes as an extended-release tablet that you take once daily, with or without food[6]. The typical dosing schedule is:

• Recommended starting dose: 50 mg once daily
• Maximum dose: 100 mg once daily (studies show higher doses may not provide additional benefit)[7,8]

Important instructions:

• Swallow the tablet whole. Do not crush, chew, split, or dissolve the tablet as this can affect how the medication is released in your body[6].
• Take it at approximately the same time each day.
• If you miss a dose, take it as soon as you remember. If it’s almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take two doses to make up for a missed one.

Common Side Effects

Many side effects improve over time as your body adjusts to the medication. Common side effects include:

Digestive system effects:

• Nausea (occurs in about 22-41% of people)[6,9]
• Dry mouth (11-25%)[6,9]
• Constipation (9-11%)[6,9]
  • Increasing fluid and fiber intake may help with constipation[10,11]
• Decreased appetite (5-10%)[6,9]
• Vomiting (4-6%)[6,9]

Other common side effects:

• Dizziness (10-16%)[6,9]
• Sweating (10-14%)[6,9]
• Insomnia or sleep problems (9-12%)[6,9]
• Fatigue (7-10%)[6,9]
• Sexual effects such as decreased libido or delayed orgasm (3-6%)[6,9]
• Increased blood pressure (1-3%)[6,12]

Desvenlafaxine is generally weight-neutral, meaning most people don’t experience significant weight changes while taking it[13,14].

Important Safety Information

Do Not Take Desvenlafaxine If:

• You are taking or have recently taken (within 14 days) medications called MAOIs (monoamine oxidase inhibitors)[6]
• You have had an allergic reaction to desvenlafaxine, venlafaxine, or any components of the formulation[6]

Talk to Your Doctor Before Taking Desvenlafaxine If You Have:

• High blood pressure or heart problems[6,12]
• Kidney or liver problems[6,15]
• History of seizures[6]
• Bipolar disorder[6]
• Glaucoma (increased pressure in the eye)[16,17]
• Bleeding problems or if you take blood thinners[18,19]
• Low sodium levels[6,20]
• If you are pregnant, planning to become pregnant, or breastfeeding[6,21,22]

Avoid While Taking Desvenlafaxine:

• Alcohol (can increase risk of side effects)[6]
• Other medications that increase serotonin levels without talking to your doctor first
• NSAIDs (like ibuprofen) or aspirin may increase bleeding risk when combined with desvenlafaxine[18,19]
• Driving or operating machinery until you know how this medication affects you

When to Contact Your Doctor Immediately

Contact your healthcare provider right away if you experience:

• Unusual changes in behavior, thoughts of suicide, or worsening depression
• Signs of serotonin syndrome: agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, muscle stiffness or twitching, trouble with coordination, nausea, vomiting, or diarrhea[6]
• Unusual bleeding or bruising[18,19]
• Severe headache, significant increase in blood pressure[6,12]
• Vision changes or eye pain[16,17]
• Severe allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing
• Seizures[6]

Starting and Stopping the Medication

Starting: It may take 2-4 weeks before you notice the full benefits of this medication. Continue taking it even if you don’t feel better right away.

Stopping: Do not stop taking desvenlafaxine suddenly without talking to your doctor. A gradual reduction in dose over 2-4 weeks is typically recommended to reduce the risk of discontinuation symptoms[6,23,24].

Possible discontinuation symptoms include:

• Dizziness
• Nausea
• Headache
• Irritability
• Fatigue
• Electric shock-like sensations
• Anxiety
• Insomnia

Special Considerations

Pregnancy and Breastfeeding

• Limited information is available about the safety of desvenlafaxine during pregnancy[6,21]
• The medication does pass into breast milk. Talk to your doctor about the risks and benefits if you are breastfeeding[6,22]

Older Adults

• No special dosage adjustments are needed for older adults based on age alone, but your doctor will monitor you more closely for side effects like low sodium levels[6,20]

Kidney Problems

• If you have severe kidney problems, your doctor may recommend a lower dose of 50 mg every other day[6,15]

References

1. Sansone, R. A., & Sansone, L. A. (2014). Serotonin norepinephrine reuptake inhibitors: A pharmacological comparison. Innovations in Clinical Neuroscience, 11(3-4), 37-42.
2. Deecher, D. C., Beyer, C. E., Johnston, G., et al. (2006). Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. Journal of Pharmacology and Experimental Therapeutics, 318(2), 657-665.
3. Perry, R., & Cassagnol, M. (2009). Desvenlafaxine: A new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder. Clinical Therapeutics, 31(1), 1374-1404.
4. Seo, H. J., Sohi, M. S., Patkar, A. A., et al. (2010). Desvenlafaxine succinate: A newer antidepressant for the treatment of depression and somatic symptoms. Postgraduate Medicine, 122(1), 125-138.
5. Clayton, A. H., Kornstein, S. G., Rosas, G., et al. (2009). An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder. CNS Spectrums, 14(3), 144-154.
6. Food and Drug Administration. (2023). PRISTIQ® (desvenlafaxine) extended-release tablets – Prescribing information.
7. Liebowitz, M. R., Tourian, K. A., & Hwang, E. (2013). A randomized, double-blind, placebo-controlled study assessing the efficacy and tolerability of desvenlafaxine 10 and 50 mg/day in adult outpatients with major depressive disorder. BMC Psychiatry, 13, 94.
8. Tourian, K. A., Padmanabhan, S. K., Groark, J., et al. (2009). Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: An 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies. Clinical Therapeutics, 31(1), 1405-1423.
9. Clayton, A. H., Tourian, K. A., Focht, K., et al. (2015). Desvenlafaxine for the prevention of relapse in major depressive disorder: Results of a randomized trial. Journal of Clinical Psychiatry, 76(5), 562-571.
10. Anti, M., Pignataro, G., Armuzzi, A., et al. (1998). Water supplementation enhances the effect of high-fiber diet on stool frequency and laxative consumption in adult patients with functional constipation. Hepato-Gastroenterology, 45(21), 727-732.
11. Markland, A. D., Palsson, O., Goode, P. S., et al. (2013). Association of low dietary intake of fiber and liquids with constipation: Evidence from the National Health and Nutrition Examination Survey. American Journal of Gastroenterology, 108(5), 796-803.
12. Thase, M. E., Shelton, R. C., Cornelius, J. R., et al. (2013). Cardiovascular safety of desvenlafaxine in major depressive disorder: Results from the corrected QT interval study. Journal of Clinical Psychopharmacology, 33(5), 672-675.
13. Coleman, C. C., Karyekar, C. S., Roscoe, R., et al. (2010). Efficacy and safety of desvenlafaxine over 8 weeks in a moderate depressive episode: A post hoc pooled analysis. International Journal of Psychiatry in Clinical Practice, 14(4), 245-254.
14. DeMartinis, N. A., Yeung, P. P., Entsuah, R., et al. (2007). A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder. Journal of Clinical Psychiatry, 68(5), 677-688.
15. Nichols, A. I., Richards, L. S., Behrle, J. A., et al. (2011). The pharmacokinetics and safety of desvenlafaxine in subjects with chronic renal impairment. International Journal of Clinical Pharmacology and Therapeutics, 49(1), 3-13.
16. Narayanan, V. (2019). Ocular adverse effects of antidepressants – Need for an ophthalmic screening and follow up protocol. Ophthalmology Research: An International Journal, 1-6.
17. Wiciński, M., Kaluzny, B. J., Liberski, S., et al. (2019). Association between serotonin-norepinephrine reuptake inhibitors and acute angle closure: What is known? Survey of Ophthalmology, 64(2), 185-194.
18. McFarland, D., Merchant, D., Khandai, A., et al. (2023). Selective serotonin reuptake inhibitor (SSRI) bleeding risk: Considerations for the consult-liaison psychiatrist. Current Psychiatry Reports, 25(3), 113-124.
19. Rahman, A. A., Platt, R. W., Beradid, S., et al. (2024). Concomitant use of selective serotonin reuptake inhibitors with oral anticoagulants and risk of major bleeding. JAMA Network Open, 7(3), e243208.
20. Gheysens, T., Van Den Eede, F., & De Picker, L. (2024). The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds. European Psychiatry, 67(1), e20.
21. Jiang, H., Xu, L., Li, Y., et al. (2016). Antidepressant use during pregnancy and risk of postpartum hemorrhage: A systematic review and meta-analysis. Journal of Psychiatric Research, 83, 160-167.
22. Sriraman, N. K., Melvin, K., Meltzer-Brody, S., et al. (2015). ABM Clinical Protocol #18: Use of antidepressants in breastfeeding mothers. Breastfeeding Medicine, 10(6), 290-299.
23. Horowitz, M. A., Framer, A., Hengartner, M. P., et al. (2023). Estimating risk of antidepressant withdrawal from a review of published data. CNS Drugs, 37(2), 143-157.
24. Rosenbaum, J. F., Fava, M., Hoog, S. L., et al. (1998). Selective serotonin reuptake inhibitor discontinuation syndrome: A randomized clinical trial. Biological Psychiatry, 44(2), 77-87.

Disclaimer: This guide is for general informational purposes and is not a substitute for professional medical advice. Always discuss any questions about your medication with your healthcare provider.