Does trazodone alone cause serotonin syndrome? (3+ cautions)

In this article, we will discuss whether using trazodone alone causes serotonin syndrome, what are the symptoms of serotonin syndrome, what research suggests, what factors can contribute to serotonin syndrome caused by trazodone, and what to do if you experience this side effect.

Does trazodone alone cause serotonin syndrome?

Yes, trazodone can cause serotonin syndrome when used in higher or more frequent doses. Trazodone is an antidepressant that belongs to the serotonin antagonist and reuptake inhibitor (SARI) class. It works by increasing serotonin levels in the brain and helps treat depression. (1)

Trazodone has a tendency to cause serotonin syndrome in individuals who have been using it for a long time or taking higher doses. It is a life-threatening condition that occurs when the levels of serotonin are increased in the brain. (2,3)

It is an FDA-approved drug to treat major depressive disorders, and its non-FDA-approved use includes the treatment of insomnia. (1)

What are the symptoms of serotonin syndrome?

Serotonin syndrome can manifest with a variety of symptoms, including: (2,3)

  • Agitation
  • Rapid heartbeat
  • Elevated blood pressure
  • Dilated pupils
  • Hallucinations
  • Altered mental state
  • Dizziness
  • Flushing
  • Sweating
  • Tremors
  • Restlessness
  • Shivering and muscle twitching
  • Incoordination and difficulty walking
  • Nausea
  • Vomiting
  • Diarrhea

How does trazodone cause serotonin syndrome?

Trazodone causes serotonin syndrome by increasing the levels of serotonin in the synaptic cleft. It mainly inhibits the serotonin transporter and acts as an antagonist of serotonin type-2 receptors. (1,2) Trazodone can also cause serotonin syndrome by interacting with other medications or by concomitant use of serotonergic drugs, e.g., Citalopram. (3)

Several factors can contribute to the serotonin syndrome caused by trazodone. However, individual responses to medication can vary, so if you experience any of the above symptoms, talk to your healthcare provider.

What does research suggest?

Serotonin syndrome is mainly caused by serotonergic drugs, either alone or in combination. Trazodone is capable of causing mild serotonin syndrome as a side effect when used alone in therapeutic doses. (3,4,)

A case of serotonin syndrome was reported in 2015 in the Case Reports of Gastroenterology; the patient was taking trazodone and duloxetine at home and was given fentanyl following a liver biopsy. (5)

Research on trazodone-induced serotonin syndrome is limited. While studies and case reports suggest a potential link between trazodone and serotonin syndrome, the incidence of serotonin syndrome with trazodone is low. However, caution is still warranted, especially when trazodone is used in conjunction with other medications.

What are the diagnostic criteria for serotonin syndrome?

Serotonin syndrome can be fatal, so it’s essential to know when serotonergic side effects at therapeutic doses become serotonin toxicity. The diagnostic criteria include the following: (4,6)

  • Spontaneous clonus
  • Inducible clonus or ocular clonus
  • Agitation
  • Hyperthermia
  • Tremors
  • Hypertonia
  • Hyperreflexia

What factors can contribute to serotonin syndrome when using trazodone alone?

Several factors can contribute to the development of serotonin syndrome in individuals taking trazodone alone:

  • Dosage: Trazodone can cause serotonin syndrome in therapeutic doses, but the risk is increased by several folds when higher doses of trazodone are administered. (8)
  • Individual variability: Variations in how the body metabolizes trazodone can also increase the risk of serotonin syndrome. Genetics can also play a role.
  • Pre-existing conditions: Individuals with certain mental conditions, which can alter the levels of neurotransmitters in the brain or the metabolism of drugs, may be more susceptible to serotonin syndrome.

What to do if you experience serotonin syndrome?

Consult your healthcare provider regarding any unwanted symptoms that you are experiencing. Your doctor might lower the dose to alleviate the symptoms if they are mild. If you suspect you are experiencing serotonin syndrome while taking trazodone, it is crucial to seek immediate medical attention. Your doctor might follow these strategies to manage your symptoms. (4,10)

  • Discontinuing trazodone: Discontinuation of trazodone may be necessary. Your doctor might consider discontinuing the causative agent if your symptoms are severe.
  • Antidote: In severe cases of serotonin syndrome, when supportive care and sedation fail, cyproheptadine is used as an antidote to reduce the symptoms. (9)
  • Sedation: The severity of your symptoms may demand sedation by using benzodiazepines, e.g., lorazepam or diazepam.


From my perspective, the risk of serotonin syndrome with trazodone alone is low so it is essential to report any unwanted symptoms to your healthcare provider so that adjustments can be made to your treatment plan.

Open communication with your healthcare provider, awareness of potential symptoms, and immediate medical attention are key components of ensuring the safe and effective use of trazodone.


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Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Simon LV, Keenaghan M. Serotonin Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Trazodone hydrochloride, a prescribing guide by The U.S. Food and Drug Administration, Available from:


Serotonin syndrome (serotonin toxicity), Serotonin syndrome (serotonin toxicity), Edward W Boyer, MD, PhD, Erica L Liebelt MD, FACMT, Michael Ganetsky, MD, Available from:


Gaffney, R. R., & Schreibman, I. R. (2015). Serotonin Syndrome in a Patient on Trazodone and Duloxetine Who Received Fentanyl following a Percutaneous Liver Biopsy. Case Reports in Gastroenterology, 9(2), 132-136.


Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2012). Serotonin Syndrome. The Ochsner Journal, 13(4), 533-540.


Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008 Sep;7(5):587-96. doi: 10.1517/14740338.7.5.587. PMID: 18759711.


Gillman PK. Serotonin syndrome: history and risk. Fundam Clin Pharmacol. 1998;12(5):482-91. doi: 10.1111/j.1472-8206.1998.tb00976.x. PMID: 9794145.


Gillman, P. K. (1999). The serotonin syndrome and its treatment. Journal of Psychopharmacology.


Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2012). Serotonin Syndrome. The Ochsner Journal, 13(4), 533-540.

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