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Trazodone Withdrawal Symptoms, (Oleptro, Desyrel Dividose) Adverse Effects, Treatment Help

Last Updated on May 13, 2024 by Carol Gillette

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

Medical professionals may not have taken the time to inform themselves or their patients about the potential complications of trazodone withdrawal.

While trazodone is often considered safer than narcotic sedatives, potential trazodone adverse effects and withdrawal complications may not have been explained adequately by prescribers.3

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Trazodone’s Black Box Warning?

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Can Trazodone Withdrawal Cause Adverse Symptoms?

Some persons may experience very little in the way of trazodone withdrawal symptoms, particularly during gradual cessation. Others may have more noticeable reactions, and some persons may suffer from protracted withdrawals that can last anywhere from 6 weeks to years if not properly treated.1,13

WARNING:  Abruptly stopping an antidepressant drug can often induce intense withdrawals that can last for a very long time, and may significantly increase the time required for complete recovery.

Commonly reported adverse trazodone withdrawal symptoms are similar to most other antidepressant drugs, with effects that can range from mild to moderate to severe and long-lasting.

Trazodone withdrawal symptoms include:
  • Suicidality 3,8,12,13
  • Hypomania, hallucination 11
  • Anxiety, depression 8,9,11,13
  • Mood swings, anger, aggression, irritability, crying spells, agitation 8,10,11,13
  • Brain zaps, the sensation of electrical shock or jolts 11,13
  • Diaphoresis (excessive sweating) 9
  • Impaired concentration, brain fog 11,13
  • Impaired memory 11
  • Insomnia, hypersomnia 8,11,13
  • Dizziness 8,13
  • Nausea, vomiting, gastrointestinal symptoms, diarrhea 9,13
  • Insomnia, disturbed sleep, vivid dreams 8-11
  • Depersonalization, de-realization 9,11
  • Pathological gambling 11
  • Akathisia 13
  • Headaches 8,13
  • Muscle aches, weakness 13

Why Do You Need to Get Off Trazodone Gradually?

Trazodone is classed as a SARI antidepressant (serotonin antagonist reuptake inhibitor). Trazodone is solely approved to be prescribed for depression but is more frequently used off-label for a wide range of other uses. It is concerning that all antidepressants (including trazodone) carry a black box warning for the heightened risk of suicide.3,8,12-14,21

SARI drugs are thought to block serotonin from adhering to 5-HT2 receptors. However, trazodone at low doses acts as a serotonin agonist (mimics serotonin) and only becomes a serotonin antagonist (blocks serotonin) at high doses. Low doses of trazodone are typically prescribed for insomnia, and higher doses are typically used in the treatment of depression. After neurochemical expression, serotonin would normally be broken down and recycled. Blocking the reabsorption of neurochemicals causes these suspended molecules to eventually degrade and become useless waste products. As with all antidepressant agents that are serotonergic, a deficit in vital levels of serotonin will often result, leading to worsening depression over time. SARI drugs such as trazodone are also thought to alter or block dopamine, histamine, acetylcholine, norepinephrine, and other neurochemicals, and disrupt the normal distribution of these natural neurochemicals in the brain and along the nerve channels of the CNS.6

Before trazodone withdrawal, make sure you adequately research and understand as much as possible to enable informed decisions. Be prepared, and ready to seek medical help if the drug you were prescribed isn’t helping, or if your symptoms are worsening. Below is a body of information that may help to provide the most-searched-for answers about trazodone adverse effects, trazodone withdrawal symptoms, and other relevant data.

Testimonial
Trazodone Withdrawal
Success

At ATMC I was always supported. The staff was great at providing opportunities for me to work towards stability. What helped me here was always keeping a positive outlook and the constant encouragement and reminders to keep faith in myself.

-Jackie

Trazodone Withdrawal is a Specialty at Alternative to Meds Center

Alternative to Meds Center delivers safe and gentle trazodone withdrawal under the care of medical doctors and licensed caregivers, and therapists. What sets Alternative to Meds apart is that getting off a drug is done within a larger, comprehensive program that addresses the root cause of one’s original symptoms. Resolving the root causes of symptoms reduces or eliminates the need for prescription drugs. The process improves one’s overall mental and physical health. We invite you to read further for more details on the exact protocols and the science behind them, that are used in-patient at Alternative to Meds Center.

What Is Trazodone Used For?

Trazodone is a generic drug sold under the brand names Desyrel and Oleptro (now discontinued). Drugmakers also produced a time-release version, called Desyrel Dividose. The FDA approved trazodone solely for the treatment of MDD (major depressive disorder). Off-label uses include insomnia, generalized anxiety disorder, bulimia, dementia, other CNS degeneration diseases such as Alzheimer’s, schizophrenia, chronic pain, diabetic neuropathy, fibromyalgia, headache, PTSD, sleep apnea, and is also used as a sedative during cocaine, benzodiazepine or alcohol withdrawal. It should be noted that after use for alcohol withdrawal, alcohol consumption did not decrease once trazodone was discontinued according to published research in 2008.25 Restoring health issues after heavy alcohol use typically involves more than a simple cessation program in many cases. Trazodone is also prescribed off-label for pain syndromes, panic disorder, and OCD (obsessive-compulsive disorder).6,14,21

Note:  Many effective non-drug-based trazodone alternatives exist, that your physician has not told you about, and perhaps did not know about. Please ask us about these.

Stopping Trazodone:  Important Info Regarding Trazodone Withdrawal

know the risks of abrupt trazodone withdrawalTrazodone has a relatively short half-life that is estimated to range somewhere between 3 and 9 hours, or longer. Trazodone withdrawal symptoms may begin within a day or a day and a half of the last dose. These figures do not apply to a time-release version of the drug such as Desyrel Dividose time-release tablets as the mechanism of action is different.

Abrupt trazodone withdrawal, stopping trazodone all at once or too quickly can cause a rebound effect in symptoms. This is common, especially if targeted nutritional support is not provided during trazodone withdrawal. Medical consensus recommends slow and gradual trazodone withdrawal accompanied by adequate nutritional support for both safety and comfort.1,8

Certain factors may influence how intense withdrawal can be for an individual, such as how long the drug was taken, the general health of the individual, and how high the dosage was. Taking trazodone for long periods of time may result in trazodone dependence and requires medical oversight for a safe and more comfortable experience. Protracted withdrawal symptoms are those that emerge and linger 6 weeks or more after discontinuation, and can last months, or even years. Medical research has been slow to report on protracted withdrawals. For too long, antidepressant withdrawal symptoms were erroneously regarded as new or re-emerging mental illnesses. The evidence now clearly shows clearly that antidepressant withdrawals are actual, and not re-emerging or newly emerging mental illnesses. The proper handling and resolution of antidepressant withdrawal phenomena requires understanding the medical factors involved.13

Always consult your prescribing physician or other competent medical practitioners before stopping trazodone or any antidepressant drug so you receive the best care possible.

Trazodone Adverse Effects

The adverse effects that occur resemble those of other antidepressants. Symptoms can be mild or more severe, at times requiring immediate medical attention.

Trazodone’s adverse effects may include:
  • Seizures 18
  • Serotonin syndrome and NMS 3,12,14,21
  • Impaired cognitive function, impaired motor controls 3,12,16
  • Increased depression, clinical worsening 3,12,21
  • Fatigue, somnolence 14,17
  • Suicidal thoughts & behavior 3,12,14,17,21
  • Cardiac arrhythmia, QT prolongation, torsades, and other cardiac risks 3,12,14,17,21
  • Panic attacks, panic symptoms 6
  • Mania, hypomania 3,7,12,14,21
  • Hyponatremia 3,12,14,21
  • Akathisia 3,12
  • Dry mouth 14
  • Blurred vision 3,12
  • Dry mouth 3,12,17
  • Dizziness or lightheadedness 14,17,21
  • Drowsiness, tiredness, fatigue 3,12,14,17
  • Headache 14,17
  • Anxiety, agitation, hostility, nervousness, irritability, aggression 3,12,14,15,17
  • Nausea, vomiting 3,12
  • Constipation, diarrhea 3,12,21
  • Priapism (a persistent painful erection) 3,12,14,17,21
  • Visual hallucinations 14
  • Abnormal bleeding 3,12,21

Some of these reactions may require immediate medical attention such as severe allergic rash, seizures, cardiovascular events, or any other severe or life-threatening event.

Trazodone FAQs

The following section addresses some of the most commonly asked questions and searches for information about trazodone.

Is Trazodone a Sleeping Pill?

Trazodone is classed as a SARI type of antidepressant. The letters stand for Serotonin Antagonist Reuptake Inhibitor. SARI drugs also block adrenergic receptors. Trazodone could also be classed as a hypnotic/anxiolytic (similar to a benzodiazepine) and is prescribed off-label for insomnia or other sleep issues, such as nightmares. Trazodone was not specifically designed (or licensed) as a sleeping pill but it has become one of the most frequently prescribed drugs for insomnia. Options for drug-free choices are becoming more widely available for overcoming sleep disturbances, which could be preferable to prescription drugs that did not provide the help you were looking for.2,4,5

Is Trazodone a Narcotic?

Technically, a narcotic is any drug that affects mood, induces sleep, or numbs pain or other unwanted sensations. The word narcotic comes from the Greek “narko,” which means to numb pain. In a legal sense, the word narcotic most often refers to an illegal psychoactive substance. In medical usage, the word has come to generally refer to opioids such as heroin or morphine. While there are similarities in effect between trazodone and narcotics, legally there is a distinct difference because trazodone is an uncontrolled substance in the US, and is not illegal to possess when it is a prescribed medication. Trazodone is not classed as a “narcotic” for legal purposes but does share narcotic properties including addiction potential, dependence, tolerance, sleep induction, and CNS suppression resident in drugs that are legally classified as “narcotics.”

How Does Trazodone Work in the Body/Brain?

Though drug regulators clearly state they don’t fully understand how it works, the mechanism of action of trazodone is thought to involve preventing serotonin and other neurotransmitters from binding to the receptors that these would normally bind to, interact with, or be attracted to. No drug can create neurotransmitters such as serotonin, norepinephrine, or dopamine. Drugs can only interfere with how they travel or are prevented from traveling along the neuron pathways of the brain and central nervous system.

As an example, when serotonin becomes trapped in the synaptic regions, this is associated with a euphoric lift in mood. Any such trazodone reactions are artificial, and temporary until the serotonin breaks down, metabolizes, (becomes inert), and is cleared as waste material.

Does Trazodone Show up on Drug Tests?

Yes, trazodone can show up on drug tests. However, it is unlikely to be screened for in the multipanel drug tests that are commonly used, for example, in the workplace.

How Long Does it Take for Trazodone to Wear Off?

There are numerous factors to consider. One is the estimated vs actual half-life of trazodone, and another is when trazodone is taken, either before retiring or during the day, and another factor appears to be dose-related.

At 50mg, half of the dosage (half-life) will be out of the system in anywhere from 3 to 6 hours, according to an extensive review of clinical research published in the Journal of Innovations in Clinical Neuroscience, authored by Jaffer et al in 2017. However, research published in 1982 showed that at 150 to 800mg, the dosages recommended for the treatment of depression, the half-life may be anywhere from 1 to 12 hours.4,25

Additionally, 50mg trazodone was found to lose its sleep-inducing effects after one week of continuous use, taken 30 minutes before retiring. As one trial showed, no difference was found after one week between trazodone and placebo for sleep latency. In another trial, participants reported sleeping longer once they did fall asleep when dosages were increased significantly over a period of 28 days. But significant after-effects of drowsiness, and cognitive and motor impairments were reported for 50mg as well as higher doses, 3X to 12X higher. At all dose levels, participants reported moderate to significant daytime drowsiness. These trials suggest that the effects of trazodone may not always wear off by the next day, regardless of the dosage taken.24

Is Trazodone a Benzo (benzodiazepine)?

No. Benzodiazepine drugs are understood to influence the transmitters called GABA. Trazodone is thought to affect other natural brain chemicals primarily. However, some of the adverse effects of both drugs overlap. Benzodiazepine drugs are recommended for only very short-term use, according to FDA and other regulatory guidelines. Trazodone is often prescribed for much longer periods of time, and doctors sometimes prescribe trazodone as a benzodiazepine alternative. Trazodone is also used as a bridge medication to help people who are having difficulty getting off benzodiazepines.

Can Trazodone Cause Serotonin Syndrome?

Yes, any agent which causes an excess build-up of active serotonin in the central nervous system can induce “serotonin syndrome.” 3 This reaction is considered potentially life-threatening and medical intervention is required, without delay 19,20. Usually one of the first treatments is to withdraw the drug. This is the one exception where stopping trazodone abruptly is recommended, as doing so can be life-saving in this case. Some symptoms of serotonin syndrome to watch for include:

  • Sudden fever
  • Seizure
  • Coma
  • Loss of consciousness
  • Rash
  • Hives
  • Itching
  • Difficulty breathing
  • Agitation
  • Delirium
  • Pressured speech
  • Significant drop and dramatic swings in blood pressure
  • Fainting
  • Agitation
  • Diarrhea
  • Mental confusion
  • Muscle rigidity
  • Sweating, hyperthermia (99.9° F+ or 37.7°C +)
  • Twitching muscles
  • Tremors
  • Shivering
  • Tachycardia (elevated heart rate)
  • Respiratory failure
  • Renal failure
  • Blod clotting
  • Hyperactive bowel sounds

Treatment for Trazodone Dependence and Abuse?

Proper treatment for long-term trazodone dependence can help, especially where the withdrawal symptoms are intense and extremely difficult to endure. Although trazodone is promoted as not habit-forming, the actuality is that once the body becomes accustomed to the presence of the drug over time, very likely a reaction will occur when the drug is withdrawn. Whether this is called dependence or addiction, trazodone withdrawal should be gradual.

There are many trazodone withdrawal treatment protocols that can lessen the severity of symptoms and accelerate the normalization of neurotransmitter health after developing trazodone dependence.

holistic inpatient withdrawal sedona drug rehabAlternative to Meds Center’s medical staff has refined the trazodone withdrawal treatment process both during and after slow and safe tapering is accomplished. Each client is helped by preparing an individualized inpatient program consisting of many steps. Lab testing is used to assess accumulations of toxins and other factors that need to be addressed. Neurotoxic substances could include heavy metals, pesticide exposures, chemicals and cleaners from work or industrial uses as well as food additives and other toxins that tend to build up in adipose (fatty) tissue.23

The process of purging accumulated neurotoxic load, supplemented by corrective nutritional therapy, are key to client success. Lab testing is used to monitor and detect areas that may need correction. We also provide a wealth of adjunct therapies for comfort and relaxation. You can view these on our services overview page in more detail. In addition to physical therapies, psychological therapies, compassionate peer support, outdoor hiking, and other amenities provided in a pristine facility nestled at the edge of the picturesque Red Rock mountains in Sedona make Alternative to Meds a leader in the field of recovery from psychiatric prescription drugs. The root causes of mental health symptoms are investigated and resolved using natural therapies. Drug tapering using healthy supporting strategies is the best route.

An important overall step in recovery from antidepressants is rebalancing neurochemistry naturally, which can help alleviate or eliminate the original symptoms that led to prescribing antidepressant medication in the first place. An exacting series of steps are completed during our programs, informed by lab testing and other assessments to provide the best-individualized trazodone withdrawal help possible.

The process of stopping trazodone can be surprisingly mild and easy to navigate using such safe and gradual tapering protocols, with help and assistance from our team of over 40 medical doctors and caregivers. Please feel free to ask us for more information on the protocols that are provided to our clients in the Alternative to Meds Center inpatient trazodone withdrawal program.

1 (800) 301-3753 for Trazodone Withdrawal Help

Sources:

1. Otani K, Tanaka O, Kaneko S, Ishida M, Yasui N, Fukushima Y, “Mechanisms of the development of trazodone withdrawal symptoms.” International Clinical Pharmacology Journal [Internet] 1994 Summer [cited 2023 May 8]

2. Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J, “Trazodon — the antidepressant: mechanism of action and its position in the treatment of depression.” Polish Journal of Psychiatry 2011 Jul-Aug [cited 2023 May 8]

3. FDA trazodone label, “Highlights of Prescribing Information“, Revised 2017 Jun [cited 2023 May 8]

4. Jaffer KY, Chang T, Vanle B, Dang J, Steiner A, Loera N, et al., “Trazodone for Insomnia: A Systematic Review.” Innovations in Clinical Neuroscience 2017 Jul-Aug [cited 2023 May 8]

5. Mendelson W, “A review of the evidence for the safety of trazodone in insomnia.” Journal of Clinical Psychiatry 2005 Apr [cited 2023 May 8]

6. Shin JJ, Saadabadi A. Trazodone. [Updated 2020 May 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.Available from: https://www.ncbi.nlm.nih.gov/books/NBK470560/ [cited 2023 May 8]

7. Knobler HY, Itzchaky S, Emanuel D, Mester R, Maizel S. Trazodone-induced mania. Br J Psychiatry. 1986 Dec;149:787-9. doi: 10.1192/bjp.149.6.787. PMID: 3790881 [cited 2023 May 8]

8. Henssler J, Heinz A, Brandt L, Bschor T. Antidepressant Withdrawal and Rebound Phenomena. Dtsch Arztebl Int. 2019 May 17;116(20):355-361. doi: 10.3238/arztebl.2019.0355. PMID: 31288917; PMCID: PMC6637660. [cited 2023 May 8]

9. Montalbetti D, Zis A, “Cholinergic Rebound Following Trazodone Withdrawal.” Journal of Psychopharmacology Feb 88 Vol 8 Issue 1 P.73 [cited 2023 May 8]

10. Lejoyeux M, Adès J. Antidepressant discontinuation: a review of the literature. J Clin Psychiatry. 1997;58 Suppl 7:11-5; discussion 16. PMID: 9219488. [cited 2023 May 8]

11. Lerner A, Klein M, “Dependence, withdrawal, and rebound of CNS drugs – an update.” Oxford Academic Journal: Brain Communications Vol 1 Issue 1 2019 [cited 2023 May 8]

12. FDA label Oleptro (trazodone hydrochloride) extended release tablets [Feb 2010] [cited 2023 May 8]

13. Hengartner MP, Schulthess L, Sorensen A, Framer A. Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum. Ther Adv Psychopharmacol. 2020;10:2045125320980573. Published 2020 Dec 24. doi:10.1177/2045125320980573 [cited 2023 May 8]

14. 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 2023 May 8]

15. Schwasinger-Schmidt TE, Macaluso M. Other Antidepressants. Handb Exp Pharmacol. 2019;250:325-355. doi: 10.1007/164_2018_167. PMID: 30194544. [cited 2023 May 8]

16. Gonçalo AMG, Vieira-Coelho MA. The effects of trazodone on human cognition: a systematic review. Eur J Clin Pharmacol. 2021 Jun 7:1–15. doi: 10.1007/s00228-021-03161-6. Epub ahead of print. PMID: 34097124; PMCID: PMC8182348. [cited 2023 May 8]

17. 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 2023 May 8]

18. Lefkowitz D, Kilgo G, Lee S. Seizures and Trazodone Therapy. Arch Gen Psychiatry. 1985;42(5):523. doi:10.1001/archpsyc.1985.01790280105012 [cited 2023 May 8]

19. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533-540. [cited 2023 May 8]

20. Bijl D. The serotonin syndrome. Neth J Med. 2004 Oct;62(9):309-13. PMID: 15635814. [cited 2023 May 8]

21. 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 2023 May 8]

22. FDA label Trazodone hydrochloride tablets for oral use. Approval 1981 [cited 2023 May 8]

23. Jackson E, Shoemaker R, Larian N, Cassis L. Adipose Tissue as a Site of Toxin Accumulation [published correction appears in Compr Physiol. 2018 Jun 18;8(3):1251]. Compr Physiol. 2017;7(4):1085-1135. Published 2017 Sep 12. doi:10.1002/cphy.c160038 [cited 2023 May 8]

24. Roth AJ, McCall WV, Liguori A. Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs. J Sleep Res. 2011 Dec;20(4):552-8. doi: 10.1111/j.1365-2869.2011.00928.x. Epub 2011 May 30. PMID: 21623982; PMCID: PMC3165092. [cited 2023 May 8]

25. Friedmann PD, Rose JS, Swift R, Stout RL, Millman RP, Stein MD. Trazodone for sleep disturbance after alcohol detoxification: a double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2008;32(9):1652-1660. doi:10.1111/j.1530-0277.2008.00742.x [cited 2023 May 8]

26. Bryant SG, Ereshefsky L. Antidepressant properties of trazodone. Clin Pharm. 1982 Sep-Oct;1(5):406-17. PMID: 6764164.[cited 2023 May 8]

Originally Published Sep 13, 2018 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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