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Long-Term Effects of Pristiq

Last Updated on November 29, 2022 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

Pristiq (desvenlafaxine), an extended-release SNRI, isn’t the most frequently prescribed antidepressant out there. The numbers are still staggering — from 2016 to 2020 the number of prescriptions doubled, and the number of patients at risk of Pristiq long-term effects tripled.4

Desvenlafaxine is the major active metabolite of venlafaxine, or Effexor XR. No significant differences have been found between Pristiq and Effexor XR, except in dosage and certain potential drug interactions that may make one drug more appropriate or better tolerated than the other.5

adhd medication withdrawal

Do Your Symptoms Require Pristiq?
An estimated 350 million people around the world are suffering from a depressed state.6 A person suffering the loss of a spouse, loss of joie de vivre, or slipping into despair and hopelessness, is in a truly vulnerable state.

Can we say with certainty that the best treatment is a chemical intervention?12 How can we even suggest such a thing before isolating specific, treatable factors that can reverse symptoms without drugs? But what if the long-term effects of drug therapy also did damage? Is there any path to authentic recovery? Yes. Our published success has been documented by independent research. We are a group of dedicated medical professionals at Alternative to Meds Center, and we are here to help.

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Pristiq’s Mechanism of Action

As is the case for ALL antidepressant medications, drug regulators and drugmakers say they do not know the exact mechanisms of action of Pristiq. In researching this subject, one finds prevalent use of terms like “belief,” “suppose,” “suggested,” “expectation,” “prediction,” “possibly,” “assumed,” “it is thought,” “theory,” and similar, as opposed to “demonstrated,” “proven,” “conclusive,” “shown,” “documented,” or “verified.” pristiq questionable mechanism of actionOpinion and laboratory studies on animals seem to be the most prevalent bases for the various theories.10

The drug label suggests the belief that SNRIs target the neurotransmission of serotonin, norepinephrine, and to a lesser extent, dopamine molecules. These 3 natural chemicals are produced by the body. The mechanism of action is suggested that Pristiq binds to certain receptors, disabling their capacity to transmit these 3 specific molecules, while not affecting other types of molecules. In the case of Pristiq, the molecules of serotonin, norepinephrine, and dopamine are blocked and prohibited from being recycled as would otherwise occur. The idea is that there ensues a build-up of activated molecules, and the theory is that perhaps due to a deficiency that may exist in the depressed person, this artificial build-up may have some therapeutic effects. These molecules, however, are subject to degradation and will be lost, leading to an eventual deficiency over time.22 The “chemical imbalance” theory entrenched behind the massive use of antidepressant medications has never been proven, though it has sold an awful lot of drugs.11,12

Are There Positive Long-term Effects of Pristiq?

pristiq no positive long term effectsLong-term drug therapy, typically referred to as “maintenance,” is the most commonly used strategy in the treatment of depression.8 Clinical studies on long-term antidepressant use, in general, are rare. Despite this, international recommendations continue to suggest treatment continue over long periods, even life-long, to avoid “relapse.” A review published in the Journal of Affective Disorders did a massive search and could only find 12 studies lasting at least ten years with reported follow-ups. The authors observed that 25% of the participants taking antidepressants reported their symptoms improved. That means that 75% did not. In the non-drug-treated group of participants, no worse outcomes were reported. No relationship could be determined between improved symptoms and drug treatment, no advantage could be associated with long-term drug therapy, and no evidence was found to support encouraging long-term antidepressant therapy.7

In contrast, brief sessions of group CBT (counseling) did have a significant protective effect over a 5.5 years-long study in reducing and preventing the recurrence of symptoms. In fact, the worse off the person’s original symptoms were, the more intensified the improvements became over the 5.5 years in those participating in brief CBT sessions.9

Clearly, the evidence for positive outcomes from long-term antidepressant therapy has not been established.

Are There Negative Long-term Effects of Pristiq?

Harms associated with long-term antidepressants, including Pristiq have been largely overlooked in the published medical literature. Mostly, clinical trials are short, and therefore only short-term effects have been reported. Sometimes short-term effects of one drug are compared with those of various other antidepressants, perhaps to assist consumers and prescribers in choosing what seems least harmful from among the thousands of antidepressants currently on the market. What is most evident is that we don’t have a very complete picture of all the potential harms because of the lack of testing on the subject.

It takes time for a history of outcomes to accumulate, and establish what trends might emerge. But we do have knowledge of some of the mechanisms of action, and this sheds some light on what can occur after SNRIs are used for years and decades.

According to published data, some of these may fade over time, but some may linger or even worsen, perhaps accounting for the very large percentage of consumers who decide to opt out of drug therapy altogether.1,2,13,14

pristiq long term effectsLong-term effects of Pristiq may include:
  • Addiction, withdrawals
  • Suicidality
  • Mood dysphoria, emotional numbing
  • Cardiovascular events and conditions
  • Organ damage in kidneys, eyes
  • Lung infections
  • Sexual dysfunction
  • Abnormal bleeding
  • Symptoms that emerged initially may linger over time*

*Symptoms associated with short-term treatment may include headaches, abdominal pain, diarrhea, constipation, insomnia, changes in appetite, anxiety, excessive sweating, nausea, dizziness, and somnolence (excessive daytime sleepiness or drowsiness).

Notes on Pristiq During Pregnancy, Breastfeeding

While data is scarce on the subject, pregnant women should attempt to research potential harm to the infant when SNRIs are taken during pregnancy, especially in the last trimester, and while breastfeeding. Up until the 1990s, caution prevailed and pregnant women were (mostly) excluded from experimental drug trials. Animals were used as a way to research but avoid negative outcomes on the fetus. A debate in the drug industry and society, in general, has continued since then, whether or not pregnant women should or should not be used in drug trials. A similar controversy about whether pregnant women should receive drug therapy also continues today. Ultimately, these are personal decisions that may be less difficult to make if enough information can be made available.

According to the FDA, infants born to mothers taking antidepressants in the 3rd trimester can be subject to difficulties breathing and feeding, which can result in prolonged hospitalization.1,15

Off-label Uses and Long-term Effects of Pristiq

Pristiq is approved to treat major depressive disorder. Off-label it is frequently prescribed for other conditions such as fibromyalgia, to prevent headaches, to prevent hot flashes in menopause, and others.13,14 Taking Pristiq for an extended time for any condition may trigger the same long-term effects referenced above.

Possible Precursors of Depression

Sometimes one needs to step out of the box to see more clearly how one has been negatively habituated, either environmentally, emotionally, nutritionally, or socially.16-21 Depression can result from quite a long list of precursors, which are not described as such in the DSM. The following gives a sampling of some extremely common examples:

  • Nutritional deficiencies, poor diet
  • Toxic exposures
  • Unsatisfactory lifestyle factors, including vocation, relationships, financial stress
  • Chronic insomnia and sleep disruption
  • Lack of sunlight
  • Lack of exercise
  • Loss of spouse, job, status, or other significant crisis or trauma

Alternative to Meds Approach to Drug-free Treatments for Depression and Other Unwanted Symptoms

Alternative to Meds has helped thousands of clients who were searching for their path toward improved mental health, including resolving the long-term effects of medications that did not help in the long run. There are so many ways to improve natural mental health, and these form the fundamental pillars of programs at the center.

rehabilitate neurochemistrySince toxic exposures related conditions are the number one culprit that we find through lab testing, cleansing accumulated neurotoxins is essential. Chronic sleep issues and exhaustion can ruin a person’s mental state, and these problems can be treated with non-pharmaceutical aids and treatment strategies, including CBT, exercise, yoga, Qi Gong, acupuncture, therapeutic massage, and many other practical interventions. Nutrition deficiencies are rampant in today’s modern diet, so we use orthomolecular medicine to remedy these issues based on individual testing, health profile, and specific diet and nutritional needs. Rehabilitating neurochemistry is an incredibly effective strategy using many non-drug-based therapies offered at the center. Safe discontinuation of drug therapy is part of recovery, under exacting and compassionate medical supervision.

You can research these strategies in much more detail on our services overview pages. We encourage researching these subjects for a thorough understanding of their importance and efficacy in improving mental wellness, naturally. Please contact us at Alternative to Meds Center to find out more about our approach to resolving the long-term effects of Pristiq, and addressing lifestyle and psychological factors that may present the path to true and authentic recovery.

1. FDA drug label Pristiq (desvenlafaxine extended release tablets) approval 2008 [cited 2022 Nov 23]

2. Naseeruddin R, Rosani A, Marwaha R. Desvenlafaxine. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Nov 23]

3. Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018 Jul;19(10):1057-1070. doi: 10.1080/14656566.2018.1491966. PMID: 30056792; PMCID: PMC6340395. [cited 2022 Nov 23]

4. Clincalc Report Desvenlafaxine Drug Usage Statistics, published online 2020 [cited 2022 Nov 23]

5. Colvert M D, Key Differences between Venlafaxine XR and Desvenlafaxine: An Analysis of Pharmacokinetic and Clinical Data published in Volume 4, Issue 1, Jan 12014 of the Mental Health Clinician Journal [cited 2022 Nov 23]

6. Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of Depression in the Community from 30 Countries between 1994 and 2014. Sci Rep. 2018 Feb 12;8(1):2861. doi: 10.1038/s41598-018-21243-x. Erratum in: Sci Rep. 2022 Sep 1;12(1):14856. PMID: 29434331; PMCID: PMC5809481. [cited 2022 Nov 23]

7. Danborg PB, Valdersdorf M, Gøtzsche PC. Long-term harms from previous use of selective serotonin reuptake inhibitors: A systematic review. Int J Risk Saf Med. 2019;30(2):59-71. doi: 10.3233/JRS-180046. PMID: 30714974; PMCID: PMC6839490. [cited 2022 Nov 23]

8. Bet PM, Hugtenburg JG, Penninx BW, Hoogendijk WJ. Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol. 2013 Nov;23(11):1443-51. doi: 10.1016/j.euroneuro.2013.05.001. Epub 2013 May 30. PMID: 23726508. [cited 2022 Nov 23]

9. Bockting CL, Spinhoven P, Wouters LF, Koeter MW, Schene AH; DELTA Study Group. Long-term effects of preventive cognitive therapy in recurrent depression: a 5.5-year follow-up study. J Clin Psychiatry. 2009 Dec;70(12):1621-8. doi: 10.4088/JCP.08m04784blu. PMID: 20141705. [cited 2022 Nov 23]

10. Sheffler ZM, Patel P, Abdijadid S. Antidepressants. [Updated 2022 Sep 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Nov 23]

11. Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017 May;4(5):409-418. doi: 10.1016/S2215-0366(17)30015-9. Epub 2017 Jan 31. PMID: 28153641; PMCID: PMC5410405. [cited 2022 Nov 23]

12. Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2022 Jul 20. doi: 10.1038/s41380-022-01661-0. Epub ahead of print. PMID: 35854107. [cited 2022 Nov 23]

13. Berhan Y, Berhan A. Is desvenlafaxine effective and safe in the treatment of menopausal vasomotor symptoms? A meta-analysis and meta-regression of randomized double-blind controlled studies. Ethiop J Health Sci. 2014 Jul;24(3):209-18. doi: 10.4314/ejhs.v24i3.4. PMID: 25183927; PMCID: PMC4141224. [cited 2022 Nov 23]

14. Cartwright C, Gibson K, Read J, Cowan O, Dehar T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Prefer Adherence. 2016 Jul 28;10:1401-7. doi: 10.2147/PPA.S110632. PMID: 27528803; PMCID: PMC4970636. [cited 2022 Nov 23]

15. Oude Rengerink K, Logtenberg S, Hooft L, Bossuyt PM, Mol BW. Pregnant womens’ concerns when invited to a randomized trial: a qualitative case control study. BMC Pregnancy Childbirth. 2015 Sep 4;15:207. doi: 10.1186/s12884-015-0641-x. PMID: 26341516; PMCID: PMC4560072. [cited 2022 Nov 23]

16. Cui Y, Gong Q, Huang C, Guo F, Li W, Wang Y, Cheng X. The relationship between sunlight exposure duration and depressive symptoms: A cross-sectional study on elderly Chinese women. PLoS One. 2021 Jul 16;16(7):e0254856. doi: 10.1371/journal.pone.0254856. PMID: 34270627; PMCID: PMC8284632. [cited 2022 Nov 23]

17. Miyake Y, Tanaka K, Okubo H, Sasaki S, Arakawa M. Dietary vitamin D intake and prevalence of depressive symptoms during pregnancy in Japan. Nutrition. 2015 Jan;31(1):160-5. doi: 10.1016/j.nut.2014.06.013. Epub 2014 Jul 19. PMID: 25466661. [cited 2022 Nov 23]

18. Baglioni C, Battagliese G, Feige B, Spiegelhalder K, Nissen C, Voderholzer U, Lombardo C, Riemann D. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011. Epub 2011 Feb 5. PMID: 21300408. [cited 2022 Nov 23]

19. Allan BA, Dexter C, Kinsey R, Parker S. Meaningful work and mental health: job satisfaction as a moderator. J Ment Health. 2018 Feb;27(1):38-44. doi: 10.1080/09638237.2016.1244718. Epub 2016 Nov 12. PMID: 27841056. [cited 2022 Nov 23]

20. Brown JS Jr. Psychiatric issues in toxic exposures. Psychiatr Clin North Am. 2007 Dec;30(4):837-54. doi: 10.1016/j.psc.2007.07.004. PMID: 17938048. [cited 2022 Nov 23]

21. Orisakwe OE. The role of lead and cadmium in psychiatry. N Am J Med Sci. 2014 Aug;6(8):370-6. doi: 10.4103/1947-2714.139283. PMID: 25210669; PMCID: PMC4158644. [cited 2022 Nov 23]

22. Siesser WB, Sachs BD, Ramsey AJ, Sotnikova TD, Beaulieu JM, Zhang X, Caron MG, Gainetdinov RR. Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant mice. ACS Chem Neurosci. 2013 Jan 16;4(1):84-8. doi: 10.1021/cn300127h. Epub 2012 Oct 1. PMID: 23336047; PMCID: PMC3547473. [cited 2022 Nov 23]

Originally Published November 29, 2022 by Diane Ridaeus

This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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