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Last updated: May 12, 2021
5 min read

Trazodone: warnings, side effects, and more

Disclaimer

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

If you’ve ever experienced depression, you know that it’s not just a mood. It’s a condition that affects your ability to eat, sleep, and function on a day-to-day basis.

Luckily, there is a wide range of treatment options available. While prescription drugs can be a valuable way to get how you’re feeling back on track, you should understand both the potential benefits and risks of trazodone.

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What is trazodone?

Trazodone is what’s called a serotonin antagonist and reuptake inhibitor, and is used to treat major depressive disorder.

It’s also a popular choice for treating depression associated with sleep disturbances. Trazodone works by increasing levels of available serotonin in the brain, which can alleviate symptoms of depression (NIH, 2017)

Many people with depression experience difficulty falling asleep or staying asleep, and certain antidepressants, like trazodone, can help. Sometimes, trazodone is prescribed for insomnia, even in the absence of depression. In fact, one survey found that about a quarter of all off-label antidepressant prescriptions were for trazodone and insomnia (Wong, 2017). 

Usually, higher doses are prescribed when trazodone is used as an antidepressant, and lower doses have sedative effects to alleviate insomnia (Stahl, 2014). Although trazodone isn’t a first-line treatment for people whose insomnia has no underlying medical or psychological condition, it’s a first-line treatment for people with both depression and insomnia (Schutte-Rodin, 2008).

Healthcare professionals may also prescribe trazodone to manage agitation or aggression in patients with dementia. Trazodone is available as a generic drug and sold under the brand names Desyrel (see Important Safety Information) and Oleptro.

Trazodone warnings and risks

The U.S. Food and Drug Administration issued a black box warning, their most stringent advisory, about the risks associated with trazodone (FDA, 2017): antidepressants like trazodone increase the chance of suicidal thoughts and behaviors––especially in children, teenagers, or young adults.

Families and caregivers should be aware of this risk, especially during the first few months of therapy or after a dose increase. Be on the lookout for suicidal thoughts, attempts, or other mood changes. Trazodone is not FDA-approved for use in people under 18 years of age.

Patients diagnosed with depression taking trazodone may be at an increased risk of attempting suicide or self-harm (Coupland, 2014). Your healthcare provider can work with you and family members to help monitor the severity of any depression symptoms, especially when starting the medication or after a change in dosage.

Trazodone is more likely than other antidepressants to cause mania, which are periods of elevated mood and excitability (Terao, 1993). It can also cause anxiety, agitation, panic attacks, difficulty sleeping, irritability, hostility, impulsivity, and movement disorders. These may be signs that the medication needs to be stopped or changed.

This is also the reason that trazodone should not be prescribed to anyone with a history of bipolar depression. Tell your healthcare provider if you experience any of these symptoms.  

What if I want to stop taking trazodone?

Don’t stop taking this medication without speaking to a healthcare provider first.

Abruptly stopping it may cause what’s called discontinuation syndrome (NIH, 2017). Roughly one in every five patients who’ve been on an antidepressant for at least six weeks may experience side effects from suddenly stopping treatment including nausea, flu-like symptoms, difficulty sleeping, sensory disturbances, and balance problems (Warner, 2006).

Trazodone side effects

The most common side effects of trazodone are drowsiness, nausea, dizziness, and dry mouth (Zhang, 2014). Trazodone is a sedative or hypnotic, which means it may impair motor abilities and slow your reaction time.

Trazodone is also more likely than other antidepressants (such as fluoxetine, brand name Prozac; see Important Safety Information) to cause drowsiness, dizziness, and lightheadedness (Beasley, 1991). Clinical trials have reported other side effects including blurry vision, constipation, confusion, fatigue, nervousness, tremors, and weight gain or loss (FDA, 2017).

Trazodone may cause a serious condition called serotonin syndrome, which is when serotonin levels in the body are too high. Symptoms may be mild, but can be life-threatening (Volpi-Abadie, 2013). Signs of serotonin syndrome include agitation, anxiety, restlessness, disorientation, sweating, increased heart rate, nausea, vomiting, tremor, and flushed skin.

Shaking and over-responsive reflexes are particularly common (Simon, 2020). If you experience these symptoms, seek medical attention immediately. 

Other serious side effects of trazodone include fainting, irregular heartbeat (arrhythmias), chest pain, seizures, and shortness of breath or difficulty breathing (NIH, 2017).

The side effects of trazodone are dose-dependent, so you have a higher chance of experiencing adverse effects with higher doses (Jaffer, 2017). If you’re working with a healthcare provider to manage depression, they can help find the lowest effective dose to minimize any side effects.

If you’ve ever had a heart attack or arrhythmia, you may be prescribed a lower dose of trazodone or a different medication entirely (Tisdale, 2016). Tell your healthcare provider about any medical conditions you have or drugs you’re taking before starting treatment with trazodone. 

Trazodone drug interactions

It’s more likely you’ll experience side effects if you take trazodone with certain medications.

A system in your liver called CYP3A4 breaks down trazodone (Rotzinger, 1998). Certain medicines slow this system down, which prevents your body from breaking down trazodone at the normal rate. This increases your risk of side effects due to higher levels of the drug in your system (NIH, 2017).

As mentioned earlier, taking trazodone with certain medications and over-the-counter supplements increases the risk of developing serotonin syndrome. This includes ergot derivatives, MAOIs, triptans, tricyclic antidepressants, selective serotonin reuptake inhibitors, fentanyl, lithium, and St. John’s wort (NIH, 2017).

Trazodone may also increase your risk of bleeding, especially when combined with blood thinners. This includes common painkillers like NSAIDs (nonsteroidal anti-inflammatory drugs). If you need to take blood thinners while on trazodone, your healthcare provider may adjust the dose to limit bleeding risk.

References

  1. Beasley, C. M., Jr, Dornseif, B. E., Pultz, J. A., Bosomworth, J. C., & Sayler, M. E. (1991). Fluoxetine versus trazodone: efficacy and activating-sedating effects. The Journal of clinical psychiatry, 52(7), 294–299. Retrieved from https://pubmed.ncbi.nlm.nih.gov/2071559/
  2. Coupland, C., Hill, T., Morriss, R., Arthur, A., Moore, M., & Hippisley-Cox, J. (2015). Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: Cohort study using a primary care database. Bmj, 350, H517. doi:10.1136/bmj.h517. Retrieved from https://www.bmj.com/content/350/bmj.h517
  3. Food and Drug Administration (FDA). (2017, June). Desyrel Label. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf
  4. Jaffer, K. Y., Chang, T., Vanle, B., Dang, J., Steiner, A. J., Loera, N., Abdelmesseh, M., Danovitch, I., & Ishak, W. W. (2017). Trazodone for Insomnia: A Systematic Review. Innovations in clinical neuroscience, 14(7-8), 24–34. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842888/
  5. National Institutes of Health (NIH). (2017, April 15). Trazodone: MedlinePlus Drug Information. Retrieved November 13, 2020, from https://medlineplus.gov/druginfo/meds/a681038.html
  6. National Institute of Mental Health (NIMH). (2018, February). Depression. Retrieved from https://www.nimh.nih.gov/health/topics/depression
  7. Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998;26(6):572-575. Retrieved from https://pubmed.ncbi.nlm.nih.gov/9616194/
  8. Schutte-Rodin, S., Broch, L., Buysse, D., Dorsey, C., & Sateia, M. (2008). Clinical guideline for the evaluation and management of chronic insomnia in adults. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 4(5), 487–504. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576317/
  9. Simon, L. V., & Keenaghan, M. (2020). Serotonin Syndrome. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK482377/
  10. Stahl, S. (2009). Mechanism of Action of Trazodone: A Multifunctional Drug. CNS Spectrums, 14(10), 536-546. doi:10.1017/S1092852900024020. Retrieved from https://www.cambridge.org/core/journals/cns-spectrums/article/abs/mechanism-of-action-of-trazodone-a-multifunctional-drug/336DB6B060471BA6C675337CC8AA637C
  11. Terao, T. (1993). Comparison of manic switch onset during fluoxetine and trazodone treatment. Biological Psychiatry, 33(6), 477-478. doi:10.1016/0006-3223(93)90176-e. Retrieved from https://psycnet.apa.org/record/1993-42495-001
  12. Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152. doi:10.1177/1715163516641136. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860751/
  13. Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. Serotonin syndrome. Ochsner Journal, 13(4), 533-540. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
  14. Warner, C. H., Bobo, W., Warner, C., Reid, S., & Rachal, J. (2006). Antidepressant discontinuation syndrome. American family physician, 74(3), 449–456. Retrieved from https://www.aafp.org/pubs/afp/issues/2006/0801/p449.html
  15. Wong J, Motulsky A, Abrahamowicz M, Eguale T, Buckeridge DL, Tamblyn R. Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ. 2017;356:j603. Published 2017 Feb 21. doi:10.1136/bmj.j603. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28228380/
  16. Zhang, L., Xie, W., Li, L., Zhang, H., Wang, G., Chen, D., . . . Zhao, J. (2014). Efficacy and Safety of Prolonged-Release Trazodone in Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Flexible-Dose Trial. Pharmacology, 94(5-6), 199-206. doi:10.1159/000368559. Retrieved from https://www.karger.com/Article/Abstract/368559