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Effexor XR Long-Term Effects | Guidance on Discontinuation

Last Updated on September 30, 2022 by Carol Gillette

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

For the greater part of 20 years Alternative to Meds Center has helped clients discontinue antidepressant medication in ways that are gentle and effective, without introducing further harm from prescription drugs. We have a tremendous success rate as documented by independent research documentation.

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Long-term Effects of Effexor XR include Worsened Conditions

There are very few long-term Effexor XR long-term effects studies that have been published. Antidepressants including SNRIs such as Effexor XR are sometimes taken for years or decades as a strategy to ensure future episodes of depression or other symptoms do not recur. However, there is little clinical evidence to back up this practice. One study out of the Netherlands showed that a majority of patients did better after a relapse of depression while remaining unmedicated, compared to patients who resumed antidepressant therapy.2  A relatively small, 52-week comparative trial was carried out, also in the Netherlands. The 181 depressed patients were randomized into 2 groups. One half received antidepressants and the other half received no antidepressants. Both groups received regular 15-minute consultations over the 52 weeks. At the end of the trial, the authors found no discernable difference in clinical effectiveness between the 2 groups.15

Until more long-term safety studies become available, one can still rely on SNRI research more generally. And, individual clinical case reports that are published can also enhance our understanding of the long-term effects of Effexor XR. Also of note, according to published research in the European Journal of Neuropsychopharmacology, adverse effects commonly observed in the short term tend to persist with the long-term use of SNRIs and antidepressants and thus provide additional credible information.3,13

effexor xr long-term effectsDrug-induced suicidality (suicidal thoughts) and attempted or completed suicide has been a controversial topic associated with antidepressant medications for decades. Some studies show a negative (not statistically significant) correlation and some studies show a definite correlation. The exact mechanism of antidepressant-induced suicidality has not been discovered. One theory is that where suicidality increased after initiating drug treatment the antidepressant may have increased energy and impulsivity, thereby an increased proclivity to act on suicidal thoughts.13 In some cases, the emergence of akathisia was associated with emerging suicidality and both adverse effects resolved after drug therapy was stopped.17 Another theory proposes antidepressant use worsened the level of depression, and that led to suicidal thoughts or a suicide attempt in the context of deepening hopelessness. This is often referred to as paradoxical depression, which lifts after the antidepressant is discontinued.16

Below we have collated a summary of adverse effects associated with the long-term use of SNRIs such as venlafaxine/Effexor XR.3,7,13,22

Long-term Effects of Effexor XR may include:
  • Suicide, suicidal thoughts
  • Psychotic symptoms, racing or crowded thoughts
  • Jitteriness
  • Anxiety syndrome
  • Clinical worsening of original symptoms
  • Psychomotor agitation, akathisia, tremor
  • Involuntary movements
  • Inner tension
  • Aggression, irritability, anger, emotional instability
  • Cardiotoxicity:  high blood pressure, tachycardia,
  • Angle-closure glaucoma, abnormal vision
  • Mania, hypomania
  • Insomnia, abnormal dreams
  • Profuse sweating
  • Weight gain, particularly in females
  • Nausea
  • Anorexia
  • Sedation
  • Impaired cognition, difficulty driving or operating machinery safely
  • Emotional blunting
  • Suppressed growth (height), development, and maturation
  • Somnolence
  • Dry mouth
  • Abnormal weakness, lack of energy (asthenia)
  • Constipation

Guidance for Effexor XR Discontinuation

Don’t try stopping Effexor XR on your own, and certainly not abruptly. Enlist the help of a trusted physician, or other qualified professionals to advise and monitor your progress. Some physicians are more informed than others on long-term Effexor XR effects and discontinuation methods.

Gradual Reduction:  A conservative very gradual reduction is recommended over a minimum of 4 weeks, or better, some number of months. This will lower your risk of worsened depression and minimize the risk of complications that may otherwise occur. Research has shown that abrupt discontinuation compared to a 2-4 week long timeline are both very similar in their results. The higher the dose and the longer it was taken, the more difficult the discontinuation symptoms will likely be. The milder approach to mitigate long-term Effexor XR effects is the longer timeline.7,20,21

Timing:  If Effexor XR is usually taken in the morning, continue that schedule. Do not suddenly switch to taking it before bed or randomly during waking hours.

Inpatient Care:  Speak to your physician about inpatient care. For a person who is already in a fragile condition, this may be the best option to help you meet the challenges with adequate support. Often an outpatient setting may not be able to provide the level of care that is needed, especially after long-term Effexor XR effects have become chronic.

Methods of Effexor XR Discontinuation

Each case presents unique challenges. Some persons may be taking multiple medications. In this case, a program would need to be tailored to discontinue them in a sequence that is optimum for overall safety and comfort.

Because Effexor XR is encapsulated in a time-release outer coating, when you cut into it, the extended-release characteristic is lost. Using the smallest dose tablets or substituting with a similar drug such as desvenlafaxine, which has a longer half-life and a similar molecular structure, to configure the desired reduced dose may be useful. The immediate-release version of Effexor was replaced by Effexor XR in 1993. Drug makers explained that the extended-release formula lessened the severity of nausea associated with the earlier immediate-release version of venlafaxine. This may have an impact on tolerability if switching to a non-time-release version. Where discontinuation symptoms are intolerably harsh, the prescriber may opt to cross over to a similar drug that has a longer half-life, is more easily tolerated, or for other reasons. Specific dosing and timing changes should be carefully monitored and adjusted to make the transition tolerable.9,20

Dosage reductions must be small enough to tolerate and would need to be exactly and consistently measured. This is easier with the help of the physician or pharmacist to make sure the reductions are exact. Immediate release venlafaxine is also available in an oral suspension, that in some cases, may be useful but as aforementioned, may present challenges due to its immediate vs extended release characteristics. These are issues that must be discussed carefully with an informed prescriber before implementation.23,24

More details on these and other methods of Effexor XR discontinuation can be found on our antidepressant tapering and Effexor tapering pages. Alternative to Meds Center uses many support therapies such as therapeutic massage, acupuncture, targeted nutritional therapies, and many others, to ease any discomfort that may occur as the program progresses.

Targeted nutritional therapy is a fundamental pillar of our treatment protocols before, during, and after discontinuation. This provides the CNS and the entire body with the raw materials it needs for a robust recovery to resolve the set of symptoms that preceded drug use in the first place. As clients will learn much more about in the educational classes offered during their program, nutrition is key to recovery, including restoring a healthy and functioning gut microbiome. 25,26

Effexor XR Half-life

The half-life of a drug is an important factor to consider when designing a drug discontinuation program, as beyond this window of time is when discontinuation symptoms are likely to emerge. Effexor XR comprises 2 agents that suppress the uptake of serotonin, norepinephrine, and to a lesser extent, dopamine. These agents are venlafaxine, and O-desmethylvenlafaxine. Venlafaxine has a half-life of about 5 hours, and ODV has a half-life of about 10 hours. The half-life may shift in either direction because of various influences, for example, impaired liver, dysfunctional kidneys, and other factors related to fast or slow metabolism including potential interactions with other drugs.7

Symptoms of Effexor XR Discontinuation

The drug label lists a number of symptoms that may emerge especially after long-term Effexor XR effects have developed and recommends gradual cessation to mitigate these as much as possible. The list includes brain zaps, seizures, headache, confusion, worsening anxiety, worsening depression, dizziness, insomnia, hypomania, tinnitus, rapidly changing or exaggerated emotions such as aggression, rage, crying spells, and others. While not everyone will experience these, be alert to them and let your managing physician or careworker know if you experience discomfort or concern, so your cessation program can be better tailored to your comfort and safety.7,20-23

Alternative to Meds Specializes in Addressing Long-term Effexor XR Effects and Gentle Discontinuation

At Alternative to Meds Center, we specialize in the most challenging cases involving transitioning to drug-free living. Under the careful management of over 40 qualified caregivers and medical staff, we have helped thousands of clients attain successful treatment outcomes without relying on prescription medications. Please view our services page for more detailed information on the protocols that are used at Alternative to Meds Center to end unnecessary suffering, ease the transition from prescription medication, and achieve authentic recovery. We are here to help you resolve the long-term effects associated with Effexor XR safely, effectively, and comfortably.


Sources:

1. Singh D, Saadabadi A. Venlafaxine. [Updated 2022 Jun 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535363/ [cited 2022 Sept 30]

2. 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 Sept 30]

3. Read J, Williams J. Adverse Effects of Antidepressants Reported by a Large International Cohort: Emotional Blunting, Suicidality, and Withdrawal Effects. Curr Drug Saf. 2018;13(3):176-186. doi: 10.2174/1574886313666180605095130. PMID: 29866014. [cited 2022 Sept 30]

4. Read J. How common and severe are six withdrawal effects from, and addiction to, antidepressants? The experiences of a large international sample of patients. Addict Behav. 2020 Mar;102:106157. doi: 10.1016/j.addbeh.2019.106157. Epub 2019 Nov 30. PMID: 31841871. [cited 2022 Sept 30]

5. Read J, Cartwright C, Gibson K. How many of 1829 antidepressant users report withdrawal effects or addiction? Int J Ment Health Nurs. 2018 Dec;27(6):1805-1815. doi: 10.1111/inm.12488. Epub 2018 Jun 5. PMID: 29873165. [cited 2022 Sept 30]

6. Sobieraj DM, Baker WL, Martinez BK, Hernandez AV, Coleman CI, Ross JS, Berg KM, Steffens DC. Adverse Effects of Pharmacologic Treatments of Major Depression in Older Adults [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Mar. Report No.: 19-EHC011-EF. PMID: 30964616. [cited 2022 Sept 30]

7. FDA label Effexor XR® (venlafaxine Extended Release) Capsules approval 1997 [cited 2022 Sept 30]

8. El-Mallakh RS, Briscoe B. Studies of long-term use of antidepressants: how should the data from them be interpreted? CNS Drugs. 2012 Feb 1;26(2):97-109. doi: 10.2165/11599450-000000000-00000. PMID: 22296314. [cited 2022 Sept 30]

9. Van Leeuwen E, van Driel ML, Horowitz MA, Kendrick T, Donald M, De Sutter AI, Robertson L, Christiaens T. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database Syst Rev. 2021 Apr 15;4(4):CD013495. doi: 10.1002/14651858.CD013495.pub2. PMID: 33886130; PMCID: PMC8092632. [cited 2022 Sept 30]

10. Machmutow K, Meister R, Jansen A, Kriston L, Watzke B, Härter MC, Liebherz S. Comparative effectiveness of continuation and maintenance treatments for persistent depressive disorder in adults. Cochrane Database Syst Rev. 2019 May 20;5(5):CD012855. doi: 10.1002/14651858.CD012855.pub2. PMID: 31106850; PMCID: PMC6526465. [cited 2022 Sept 30]

11. O’Neill S, Minehan M, Knight-Agarwal CR, Turner M. Depression, Is It Treatable in Adults Utilising Dietary Interventions? A Systematic Review of Randomised Controlled Trials. Nutrients. 2022 Mar 27;14(7):1398. doi: 10.3390/nu14071398. PMID: 35406011; PMCID: PMC9003461. [cited 2022 Sept 30]

12. Santarsieri D, Schwartz TL. Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs Context. 2015 Oct 8;4:212290. doi: 10.7573/dic.212290. PMID: 26576188; PMCID: PMC4630974. [cited 2022 Sept 30]

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14. Tomlinson A, Efthimiou O, Boaden K, New E, Mather S, Salanti G, Imai H, Ogawa Y, Tajika A, Kishimoto S, Kikuchi S, Chevance A, Furukawa TA, Cipriani A. Side effect profile and comparative tolerability of 21 antidepressants in the acute treatment of major depression in adults: protocol for a network meta-analysis. Evid Based Ment Health. 2019 May;22(2):61-66. doi: 10.1136/ebmental-2019-300087. Epub 2019 Apr 17. PMID: 30996028. [cited 2022 Sept 30]

15. Hermens ML, van Hout HP, Terluin B, Adèr HJ, Penninx BW, van Marwijk HW, Bosmans JE, van Dyck R, de Haan M. Clinical effectiveness of usual care with or without antidepressant medication for primary care patients with minor or mild-major depression: a randomized equivalence trial. BMC Med. 2007 Dec 7;5:36. doi: 10.1186/1741-7015-5-36. PMID: 18067659; PMCID: PMC2234409. [cited 2022 Sept 30]

16. Damluji NF, Ferguson JM. Paradoxical worsening of depressive symptomatology caused by antidepressants. J Clin Psychopharmacol. 1988 Oct;8(5):347-9. PMID: 3183073. [cited 2022 Sept 30]

17. Rothschild AJ, Locke CA. Reexposure to fluoxetine after serious suicide attempts by three patients: the role of akathisia. J Clin Psychiatry. 1991 Dec;52(12):491-3. PMID: 1752848. [cited 2022 Sept 30]

18. Reeves RR, Ladner ME. Antidepressant-induced suicidality: an update. CNS Neurosci Ther. 2010 Aug;16(4):227-34. doi: 10.1111/j.1755-5949.2010.00160.x. Epub 2010 Apr 16. PMID: 20553304; PMCID: PMC6493906. [cited 2022 Sept 30]

19. Teicher MH, Glod CA, Cole JO. Antidepressant drugs and the emergence of suicidal tendencies. Drug Saf. 1993 Mar;8(3):186-212. doi: 10.2165/00002018-199308030-00002. PMID: 8452661. [cited 2022 Sept 30]

20. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr. 2016 Jun;39(3):76-83. doi: 10.18773/austprescr.2016.039. Epub 2016 Jun 1. PMID: 27346915; PMCID: PMC4919171. [cited 2022 Sept 30]

21. Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry. 2019 Jun;6(6):538-546. doi: 10.1016/S2215-0366(19)30032-X. Epub 2019 Mar 5. PMID: 30850328. [cited 2022 Sept 30]

22. Goldsmith L, Moncrieff J. The psychoactive effects of antidepressants and their association with suicidality. Curr Drug Saf. 2011 Apr;6(2):115-21. doi: 10.2174/157488611795684622. PMID: 21375477. [cited 2022 Sept 30]

23. Campagne DM. Venlafaxine and serious withdrawal symptoms: warning to drivers. MedGenMed. 2005 Jul 6;7(3):22. PMID: 16369248; PMCID: PMC1681629. [cited 2022 Sept 30]

24. Donnelly RF, Wong K, Goddard R, Johanson C. Stability of venlafaxine immediate-release suspensions. Int J Pharm Compd. 2011 Jan-Feb;15(1):81-4. PMID: 23696051. [cited 2022 Sept 30]

25. Jeynes KD, Gibson EL. The importance of nutrition in aiding recovery from substance use disorders: A review. Drug Alcohol Depend. 2017 Oct 1;179:229-239. doi: 10.1016/j.drugalcdep.2017.07.006. Epub 2017 Aug 4. PMID: 28806640. [cited 2022 Sept 30]

26. Järbrink-Sehgal E, Andreasson A. The gut microbiota and mental health in adults. Curr Opin Neurobiol. 2020 Jun;62:102-114. doi: 10.1016/j.conb.2020.01.016. Epub 2020 Mar 9. PMID: 32163822. [cited 2022 Sept 30]


Originally Published Sept. 27, 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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