What is Serotonin Syndrome?

doctor handing medicine to a patient

The Bottom Line

Serotonin syndrome is a disorder caused by excessive serotonin activity in the human body. It often occurs after medication use and can cause potentially life-threatening symptoms including high fever, confusion, and seizures.

woman taking white pill

What is serotonin?

Serotonin is a chemical made naturally by our bodies and is often referred to as a “happy hormone.” In the brain, messenger systems that involve serotonin have an essential role in regulating our moods, stress responses, and sleep. Abnormal serotonin function can lead to depression, anxiety, and other disorders. Because of this, many common antidepressants work by increasing serotonin activity. The SSRI (selective serotonin reuptake inhibitor) class of drugs, including sertraline (Zoloft), paroxetine (Paxil), and citalopram (Celexa), work by increasing serotonin activity within the brain. There are many other medications (both prescription and over-the-counter) that can affect serotonin activity, including some pain medications, antibiotics, and dietary supplements.

What is serotonin syndrome?

While normal serotonin function is important for our well-being, too much serotonin activity can be dangerous. Excessive serotonin activity commonly occurs when people take medications that affect serotonin function. This can occur after an overdose, but it can also occur during normal therapeutic use of these medications. Serotonin syndrome is the term used to describe the potentially life-threatening medical condition that occurs due to abnormally high serotonin activity in the human body.

Which drugs can cause serotonin syndrome?

Multiple medications are associated with the development of serotonin syndrome. In addition to the SSRI class of drugs, other antidepressants such as trazodone, venlafaxine (Effexor), and buspirone (BuSpar) are also associated with this condition. Dextromethorphan, an ingredient in some over-the-counter cough suppressants such as Robitussin DM and Coricidin HBP Cough and Cold, can affect serotonin activity, as can the pain medications tramadol (Ultram) and fentanyl. Even some dietary supplements, such as St. John’s wort and tryptophan, have been implicated as potential causes of serotonin syndrome.

What are the symptoms of serotonin syndrome?

Serotonin syndrome can range from mild to life-threatening. In general, the signs and symptoms of serotonin syndrome involve abnormal vital signs (including fast heart rate and fever), increased muscle tone (ranging from abnormal muscle movements to severe tremors and muscle rigidity), and mental status changes (including confusion, agitation, and seizures). Symptoms frequently occur within hours after medication use and can worsen dramatically if an affected person continues to take the medication. Serotonin syndrome is a clinical diagnosis, meaning that there is no laboratory test that can establish its presence. Rather, patients with possible serotonin syndrome should be evaluated by a doctor, who will often make the diagnosis based on the history of medication use in addition to the patient’s clinical signs and symptoms. The treatment of serotonin syndrome includes the immediate discontinuation of any contributing medications. Benzodiazepines such as lorazepam (Ativan) or alprazolam (Xanax) can be used to treat the agitation and other manifestations of serotonin syndrome. Many patients will require hospitalization, and some might even need to be monitored in an intensive care unit. Fortunately, when serotonin syndrome is recognized and promptly treated, most patients recover without complications. However, if the diagnosis is delayed or not identified, severe illness or death can occur.

If you experience unwanted signs or symptoms after taking medications and are concerned about serotonin syndrome, do not try to manage this condition yourself. Contact your doctor or Poison Control immediately. Get a fast personalized recommendation online or call 1-800-222-1222. Both options are free, confidential, and available 24 hours a day.

Kelly Johnson-Arbor, MD
Medical Toxicologist

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Poisoned?

Call 1-800-222-1222 or

HELP ME online

Prevention Tips

  • Tell your doctor about all medications you are taking, including prescription and over-the-counter products.
  • Take all medications as prescribed. Do not take extra doses of medications unless directed to by your doctor.
  • Before starting a new medication, discuss potential side effects and drug interactions with your doctor or pharmacist.

This Really Happened

A 39-year-old man was admitted to a hospital for treatment of an infection. He had a history of opioid dependence and took methadone daily. While in the hospital, he was treated with an antibiotic (linezolid). Within a few days after starting linezolid, he became confused and disoriented and developed an erratic heart rate and increased muscle tone. Since both methadone and linezolid are known to have activity on serotonin, he was diagnosed with serotonin syndrome. Linezolid was discontinued, and he was treated with intravenous fluids and benzodiazepines. His symptoms gradually improved, and he was discharged from the hospital several weeks later (from Mastroianni & Ravaglia, 2017).

For More Information

Serotonin syndrome. Cleveland Clinic. Reviewed March 24, 2022. Accessed November 23, 2023.

Serotonin syndrome. Medline Plus. Updated April 16, 2022. Accessed November 23, 2023.


References

Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009;60:355–366.

Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–1120.

Dosi R, Ambaliya A, Joshi H, Patell R. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep. 2014;2014:bcr2014204154.

Graeff FG. Serotonergic systems. Psychiatr Clin North Am. 1997;20(4):723–739.

Mastroianni A, Ravaglia G. Serotonin syndrome due to co-administration of linezolid and methadone. Infez Med. 2017;25(3):263–266.

Mikkelsen N, Damkier P, Pedersen SA. Serotonin syndrome-a focused review. Basic Clin Pharmacol Toxicol. 2023;133(2):124–129.

Wang RZ, Vashistha V, Kaur S, Houchens NW. Serotonin syndrome: preventing, recognizing, and treating it. Cleve Clin J Med. 2016;83(11):810–817.

Poisoned?

Call 1-800-222-1222 or

HELP ME online

Prevention Tips

  • Tell your doctor about all medications you are taking, including prescription and over-the-counter products.
  • Take all medications as prescribed. Do not take extra doses of medications unless directed to by your doctor.
  • Before starting a new medication, discuss potential side effects and drug interactions with your doctor or pharmacist.

This Really Happened

A 39-year-old man was admitted to a hospital for treatment of an infection. He had a history of opioid dependence and took methadone daily. While in the hospital, he was treated with an antibiotic (linezolid). Within a few days after starting linezolid, he became confused and disoriented and developed an erratic heart rate and increased muscle tone. Since both methadone and linezolid are known to have activity on serotonin, he was diagnosed with serotonin syndrome. Linezolid was discontinued, and he was treated with intravenous fluids and benzodiazepines. His symptoms gradually improved, and he was discharged from the hospital several weeks later (from Mastroianni & Ravaglia, 2017).