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Long-Term Effects of Trazodone

Last Updated on April 25, 2024 by Carol Gillette

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

Trazodone long-term effects may outweigh the initial benefits for depression or insomnia. Depression on its own is truly debilitating. Insomnia also steals one’s joie de vivre. Often, this dreadful duo conspires relentlessly, each enemy fueling the other on a daily basis. Trazodone is frequently prescribed for a host of other conditions as well.

While a prescription may have been the only exit offered at a time of real crisis, many science-based, drug-free treatments may have been overlooked in your quest for relief. Our aim is to help you recover from persisting long-term effects of trazodone, and authentically mend the original symptoms that led to a prescription in the first place.



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About Trazodone (Oleptro© extended-release)

about trazodone long-term effectsIn trying to understand the mechanics of various antidepressants, you may have had difficulty, and perhaps run into the very grey blur of opinions, conjectures, contradictions, theories, suppositions, and the like. Testing the neurochemical effects of drugs commonly involves looking at slices of drugged and non-drugged rat or rabbit brains under various kinds of microscopes. Other methods such as forced swimming tests are carried out for weeks at a time, to determine how well antidepressants are working on the lab rats.26 Conclusions are often ambiguous, subject to interpretation, and filtered by the particular field of expertise (and sometimes, sadly, the source of funding) of the scientist whose eyeballs are doing the looking.27 A recent paper published in the Internationally peer-reviewed Journal of Molecular Psychiatry authored by Moncrieff et al boldly concluded that the use of serotonin-based antidepressants for depression is not supported by any evidence.28 It is no wonder consumers struggle to understand since even experts in the field acknowledge an imperfect understanding of such a complex subject.

Notwithstanding this lack of clarity, many antidepressants are grouped according to the neurochemicals that they are thought to alter. Trazodone falls into the SARI category. SARI drugs are described as chemicals that act as serotonin antagonists, meaning they inhibit the recycling or reuptake of serotonin molecules by inhibiting the transport mechanism. Some research shows trazodone has antagonist effects on various other transmitters such as cortisol and can affect adjacent systems as well.30 The “antagonist,” descriptor indicates how certain receptors are blocked from receiving serotonin molecules, leaving them active at the nerve synapse instead of being stored again and ready for re-use. It’s something like leaving the milk out of the fridge for too long. Eventually, the milk degrades and ends up down the drain. The analogy is not exact but describes what happens to serotonin molecules left suspended where enzymes like to move in and destroy them, resulting in unusable waste, and eventually, a likely deficiency of serotonin, a point reported by Moncrieff et al’s massive review, mentioned above.

What all of this theory actually has to do with improving mental health is under a great deal of debate as the great struggle for wellness continues.

What is trazodone prescribed to treat?

Trazodone (Oleptro© is the extended-release version) is FDA approved to treat depression.

NOTE OF CAUTION:  Serotonin syndrome must be watched for especially if other serotonergic drugs are used concurrently.1,2

Trazodone Off-label Uses

Trazodone is more frequently prescribed for insomnia than for depression.6 Trazodone’s sedative characteristics are most commonly cited as effective for insomnia, and with fewer adverse effects when taken at low doses than other antidepressants. The extremely short half-life (3-6 hrs) is thought to explain the lack of hangover effects on waking.30

Other off-label uses cover an exceptionally wide range, none of which have been thoroughly placebo-tested for long-term safety. The studies we find too short, and the sample sizes too small to reliably predict outcomes over significant time horizons. Some off-label uses include treating anxiety, reducing anxiety and other adverse effects caused by other drugs, PTSD, alcohol and benzodiazepine detox, obsessive-compulsive disorder, panic disorder, chronic pain diseases such as diabetic neuropathy, sexual dysfunction, agitation or other behavioral abnormalities related to cognitive dysfunction, dementia, Alzheimer’s disease, bulimia, other eating and feeding disorders, fibromyalgia, sleep apnea, schizophrenia, and trazodone is sometimes used alone or in combination with other drugs when no other antidepressants have shown desired efficacy.4-7,10-12,14-17,19,28

Trazodone has also become popular in veterinary clinics, for dogs and cats who are anxious about visiting the vet.19

Trazodone Long-Term Effects

Few clinical trials can be found that research the long-term effects of trazodone. The American Academy of Sleep Medicine does NOT recommend trazodone for insomnia.33 A 16-week-long trial on over 100 Alzheimer’s patients with dementia was found that reported no benefit from the daily use of trazodone on improving psychological or behavioral symptoms or achieving clinical improvements, though the drug has been prescribed off-label for this purpose. The scope of the test did not include or specify adverse effects.31

In insomnia patients, tolerance is a concern. Tolerance here refers to the point when a drug stops working. One study found that after 7 days, there was no difference between the patients taking trazodone and placebo in terms of improvements to sleep.30 Tolerance was indicated in a 6-month-long clinical trial of 137 patients, where trazodone did not improve sleep quality beyond one month of follow-ups. Whether trazodone improved sleep within the first month was not reported.32

Antidepressant-induced reactions can sometimes fade away, especially after stopping the drug. And sometimes they can persist for a long time. It would follow that potential long-term adverse effects of trazodone could encompass an extensive list of potential results after months or years of use. Not everyone will react the same way, and not every reaction may emerge at the same time. The following list includes rare and more commonly reported adverse effects of trazodone, which may persist in some persons long-term. 1-5,7-13,18,21,22

Trazodone long-term effects (including the extended-release version) may include:
  • trazodone long term effectsSuicidal ideation
  • Myoclonus (sudden, brief, involuntary jerking of groups of muscles)
  • Mania (extreme and unusual elevated mood or activity, non-stop fast-talking, can include hallucinations, unusual irritability, a flood of energy, fantastic ideas that are out of the ordinary.)
  • Agitation
  • Worsened or newly emerging anxiety
  • Worsened or newly emerging depression
  • Panic attacks
  • Psychomotor impairment (difficulty or delay executing intended muscular movements)
  • Dizziness
  • Headaches
  • Fatigue, sedation, drowsiness, excessive daytime sleepiness
  • Priapism (painful, long-lasting erection)
  • Trazodone-induced parkinsonism (symptoms resembling Parkinson’s disease include shuffling walk, tremors, stiffness, difficulties with balance and coordination)
  • Visual hallucinations
  • QT prolongation (heart takes longer to recharge between beats)
  • Orthostatic hypotension (lightheadedness or fainting after standing up from a sitting or laying position)
  • Gastrointestinal dysfunction including diarrhea, nausea
  • Liver damage
  • Arrhythmias (irregular heartbeat)
  • Dry mouth

Trazodone and Long-term Effects on Pregnancy?

There are no indications on the drug label that the use of trazodone during pregnancy increases the risks of fetal damage or birth defects. There is a paucity of information to go on as the subject is not well studied in clinical trials. Antidepressants during pregnancy should be discussed with your primary caregivers to help you come to a decision about whether it is a risk for you or your baby.

Holistic Help for Insomnia, Depression

A wealth of information is available that can be drawn upon to strategize nonpharmacologic treatments for many of the symptoms that a drug like trazodone is prescribed for. Many studies have found counseling, improved sleep hygiene, relaxation therapy, and even paradoxical intention practice have had significant efficacy for these symptoms, and these drug-free methods do not come with the added baggage of lingering adverse effects.23,24 You can find more information below in the section discussing the evidence-based holistic protocols used at Alternative to Meds Center.

Rediscover Natural Mental Wellness after Long-Term Effects of Trazodone — Protocols Used at Alternative to Meds Center

rediscover natural mental wellness sedona drug rehabAlternative to Meds Center specializes in the application of orthomolecular medicine, environmental medicine, counseling services, and many other holistic, drug-free treatments that improve mental wellness naturally. There are diet-based strategies, and herbal remedies that have been proven in clinical settings and their efficacy is as great or greater than pharmaceutical products in a great many cases.

Some examples of treatments available at Alternative to Meds Center include neurotoxin removal, neurotransmitter rehabilitation, exercise, nebulized glutathione treatments, equine-assisted therapy, co-occurring disorders counseling, peer support programs, colon hydrotherapy, drug-free pain management, and many others.

Each program is designed based on individual lab testing and other assessments, to determine the best way forward for the individual client. We welcome you to call and find out more information that you are particularly interested in. You may just find that our program is the one that you have been looking for. We are a world-class facility in Sedona, nestled at the foot of the majestic Red Rock mountains. This locale provides plenty of opportunities for outdoor activities, sightseeing, photography, and colorful shops and venues in the area. Please call us and find out how easy it may be for you to come and heal with us. You or your loved one may be suffering from a drug that perhaps left you with negative lingering after-effects, and did not successfully resolve your original symptoms. Our programs have helped thousands of clients just like you — we are here to help guide you on the true path to authentic recovery from the long-term effects of trazodone.

1 (800) 301-3753 for Help with Long-Term Effects of Trazodone

Sources:

1. FDA label Desyrel (trazodone hydrochloride) tablets for oral use, approval 1981 [cited 2022 Dec 14]

2. FDA label Oleptro (trazodone) hydrochloride extended-release tablets initial approval 1981 [cited 2022 Dec 14]

3. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry. 2005 Apr;66(4):469-76. doi: 10.4088/jcp.v66n0409. PMID: 15816789. [cited 2022 Dec 14]

4. Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470560/ [cited 2022 Dec 14]

5. James SP, Mendelson WB. The use of trazodone as a hypnotic: a critical review. J Clin Psychiatry. 2004 Jun;65(6):752-5. doi: 10.4088/jcp.v65n0605. PMID: 15291651. [cited 2022 Dec 14]

6. Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging. 1994 Apr;4(4):331-55. doi: 10.2165/00002512-199404040-00006. PMID: 8019056. [cited 2022 Dec 14]

7. Fagiolini A, Comandini A, Catena Dell’Osso M, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. doi: 10.1007/s40263-012-0010-5. Erratum in: CNS Drugs. 2013 Aug;27(8):677. PMID: 23192413; PMCID: PMC3693429. [cited 2022 Dec 14]

8. Sharma KD, Colangelo T, Mills A. Trazodone-induced parkinsonism: A case report. Int J Clin Pharmacol Ther. 2022 Apr;60(4):184-187. doi: 10.5414/CP204068. PMID: 35102822. [cited 2022 Dec 14]

9. Sarwar AI. Trazodone and Parkinsonism: The Link Strengthens. Clin Neuropharmacol. 2018 May/Jun;41(3):106-108. doi: 10.1097/WNF.0000000000000278. PMID: 29634584. [cited 2022 Dec 14]

10. Darko W, Guharoy R, Rose F, Lehman D, Pappas V. Myoclonus secondary to the concurrent use of trazodone and fluoxetine. Vet Hum Toxicol. 2001 Aug;43(4):214-5. PMID: 11474735. [cited 2022 Dec 14]

11. Finfgeld DL. Serotonin syndrome and the use of SSRIs. J Psychosoc Nurs Ment Health Serv. 2004 Feb;42(2):16-20. doi: 10.3928/02793695-20040201-04. PMID: 14982105. [cited 2022 Dec 14]

12. Looper KJ. Potential medical and surgical complications of serotonergic antidepressant medications. Psychosomatics. 2007 Jan-Feb;48(1):1-9. doi: 10.1176/appi.psy.48.1.1. PMID: 17209143. [cited 2022 Dec 14]

13. Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jabłońska J, Rybakowski J. Trazodon–lek przeciwdepresyjny: mechanizm działania i miejsce w leczeniu depresji [Trazodon–the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. Polish. PMID: 22232986. [cited 2022 Dec 14]

14. Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. 2017 Jan;129(1):140-148. doi: 10.1080/00325481.2017.1249265. Epub 2016 Oct 28. PMID: 27744763. [cited 2022 Dec 14]

15. Bossini L, Coluccia A, Casolaro I, Benbow J, Amodeo G, De Giorgi R, Fagiolini A. Off-Label Trazodone Prescription: Evidence, Benefits and Risks. Curr Pharm Des. 2015;21(23):3343-51. doi: 10.2174/1381612821666150619092236. PMID: 26088119. [cited 2022 Dec 14]

16. Yi XY, Ni SF, Ghadami MR, Meng HQ, Chen MY, Kuang L, Zhang YQ, Zhang L, Zhou XY. Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2018 May;45:25-32. doi: 10.1016/j.sleep.2018.01.010. Epub 2018 Feb 7. PMID: 29680424. [cited 2022 Dec 14]

17. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-349. doi: 10.5664/jcsm.6470. PMID: 27998379; PMCID: PMC5263087. [cited 2022 Dec 14]

18. Kalgutkar AS, Henne KR, Lame ME, Vaz AD, Collin C, Soglia JR, Zhao SX, Hop CE. Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4. Chem Biol Interact. 2005 Jun 30;155(1-2):10-20. doi: 10.1016/j.cbi.2005.03.036. Epub 2005 Apr 18. PMID: 15978881. [cited 2022 Dec 14]

19. Erickson A, Harbin K, MacPherson J, Rundle K, Overall KL. A review of pre-appointment medications to reduce fear and anxiety in dogs and cats at veterinary visits. Can Vet J. 2021 Sep;62(9):952-960. PMID: 34475580; PMCID: PMC8360309. [cited 2022 Dec 14]

20. Mittur A. Trazodone: properties and utility in multiple disorders. Expert Rev Clin Pharmacol. 2011 Mar;4(2):181-96. doi: 10.1586/ecp.10.138. PMID: 22115401. [cited 2022 Dec 14]

21. Kast RE. Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone. World J Biol Psychiatry. 2009;10(4 Pt 2):682-5. doi: 10.1080/15622970902836022. PMID: 19384678. [cited 2022 Dec 14]

22. FDA Medication Guide Oleptro (trazodone hydrochloride) extended release tablets approval 1981 [cited 2022 Dec 14]

23. Maness D, Khan M, Nonpharmacologic Management of Chronic Insomnia published in the American Family Physician 2015;92(12):1058-1064 [cited 2022 Dec 14]

24. Apóstolo J, Bobrowicz-Campos E, Rodrigues M, Castro I, Cardoso D. The effectiveness of non-pharmacological interventions in older adults with depressive disorders: A systematic review. Int J Nurs Stud. 2016 Jun;58:59-70. doi: 10.1016/j.ijnurstu.2016.02.006. Epub 2016 Feb 17. PMID: 27087298. [cited 2022 Dec 14]

25. Schott G, Pachl H, Limbach U, Gundert-Remy U, Ludwig WD, Lieb K. The financing of drug trials by pharmaceutical companies and its consequences. Part 1: a qualitative, systematic review of the literature on possible influences on the findings, protocols, and quality of drug trials. Dtsch Arztebl Int. 2010 Apr;107(16):279-85. doi: 10.3238/arztebl.2010.0279. Epub 2010 Apr 23. PMID: 20467553; PMCID: PMC2868984. [cited 2022 Dec 14]

26. Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000 Dec 15;20(24):9104-10. doi: 10.1523/JNEUROSCI.20-24-09104.2000. PMID: 11124987; PMCID: PMC6773038. [cited 2022 Dec 14]

27. Kuśmider M, Faron-Górecka A, Dziedzicka-Wasylewska M. Delayed effects of antidepressant drugs in rats. Behav Pharmacol. 2006 Dec;17(8):641-9. doi: 10.1097/FBP.0b013e3280116ea2. PMID: 17110791. [cited 2022 Dec 14]

28. 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 Dec 14]

29. Bossini L, Casolaro I, Koukouna D, Cecchini F, Fagiolini A. Off-label uses of trazodone: a review. Expert Opin Pharmacother. 2012 Aug;13(12):1707-17. doi: 10.1517/14656566.2012.699523. Epub 2012 Jun 20. PMID: 22712761. [cited 2022 Dec 14]

30. Jaffer KY, Chang T, Vanle B, Dang J, Steiner AJ, Loera N, Abdelmesseh M, Danovitch I, Ishak WW. Trazodone for Insomnia: A Systematic Review. Innov Clin Neurosci. 2017 Aug 1;14(7-8):24-34. PMID: 29552421; PMCID: PMC5842888. [cited 2022 Dec 14]

31. Martinon-Torres G, Fioravanti M, Grimley EJ. Trazodone for agitation in dementia. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004990. doi: 10.1002/14651858.CD004990. PMID: 15495135. [cited 2022 Dec 14]

32. Stein MD, Kurth ME, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial. Drug Alcohol Depend. 2012 Jan 1;120(1-3):65-73. doi: 10.1016/j.drugalcdep.2011.06.026. Epub 2011 Jul 27. PMID: 21798674; PMCID: PMC3214692. [cited 2022 Dec 14]

33. Consumer Reports Should You Take Trazodone for Insomnia? published online April 4 2021 [cited 2024 April 22]

Originally Published December 15, 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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Long-Term Effects of Trazodone
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