Serotonin syndrome occurs when a person takes drugs that cause excess levels of serotonin to accumulate in the body. Symptoms can include agitation, a dry mouth, dilated pupils, confusion, and more.

If someone experiencing serotonin syndrome does not receive treatment, the condition can lead to serious and sometimes life threatening complications. Serious complications can include:

  • seizures
  • kidney failure
  • respiratory failure
  • loss of muscle tissue

In this article, we cover the causes and symptoms that doctors associate with serotonin syndrome. We also discuss how doctors diagnose and treat serotonin syndrome.

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Serotonin syndrome refers to a collection of symptoms that develop when too much serotonin accumulates in the body.

Serotonin is a neurotransmitter that specialized cells in the brain, spinal cord, and intestines produce. Serotonin helps regulate:

  • mood and behavior
  • memory
  • sleep
  • sexual desire and function
  • digestion
  • appetite
  • blood flow
  • body temperature

Most cases of serotonin syndrome are the result of taking multiple medications or drugs together. Some people can also develop serotonin syndrome after taking a single medication that increases serotonin levels.

Doctors do not know the exact prevalence and incidence of serotonin syndrome because the condition causes a wide range of nonspecific symptoms. This makes it difficult to diagnose. A 2019 article also suggests that doctors may not be recording serotonin syndrome as often as it occurs due to a lack of awareness.

Recent evidence suggests that the incidence of serotonin syndrome is increasing alongside the increasing use of antidepressants.

For example, research from the Centers for Disease Control and Prevention (CDC) notes that between 2009 to 2010 and 2017 to 2018 there was an increase in antidepressant use from 10.6% to 13.8%. Additionally, in its 2022 annual report, the American Association of Poison Control Centers listed antidepressants as one of the five substances most frequently involved in human exposures.

Typically, serotonin syndrome occurs when people take one or more prescription medications, supplements, or illicit drugs that increase serotonin levels.

Examples of substances that increase serotonin levels include:

  • antidepressants
    • SSRIs
    • serotonin and norepinephrine reuptake inhibitors (SNRIs)
    • monoamine oxidase inhibitors (MAOIs)
    • tricyclic antidepressants (TCAs)
  • prescription migraine medications
    • triptans, such as almotriptan, naratriptan, and sumatriptan
  • anticonvulsive medications
    • carbamazepine
    • valproic acid
  • opioid pain medications
    • tramadol
    • oxycodone
    • tapentadol
  • antinausea medications
    • dolasetron
    • tropiserton
    • granisetron

Other medications and substances that increase serotonin levels include:

  • illicit drugs, including ecstasy, cocaine, and amphetamines
  • herbal supplements, such as St. John’s wort and ginseng
  • dextromethorphan (DXM), an ingredient in over-the-counter cough and cold medications, such as Delsym, Robitussin, and Mucinex DM
  • ritonavir (Norvir), an antiretroviral medication
  • lithium

Symptoms of serotonin syndrome usually present within 6 to 24 hours after ingesting the causative medication.

Symptoms of serotonin syndrome include:

Severe symptoms that experts associate with serotonin syndrome include:

  • extremely high body temperature, or hyperthermia
  • delirium
  • muscle rigidity

A doctor can diagnose serotonin syndrome by reviewing a person’s medical history, symptoms, and current medications.

They can also use one or more laboratory tests to rule out conditions that cause similar symptoms to serotonin syndrome, such as hyperthermia, meningitis, encephalitis, heatstroke, and neuroleptic malignant syndrome.

Examples of tests doctors can use during the diagnostic process include:

  • blood count test
  • electrolyte panel
  • creatine panel
  • urine tests
  • kidney, liver, or thyroid function tests
  • drug and alcohol tests
  • brain scans
  • lumbar puncture

Symptoms of serotonin syndrome usually resolve on their own once a person stops taking the medication or substance responsible for the problem. People who have severe symptoms of serotonin syndrome may require hospitalization and ongoing monitoring.

Doctors may recommend one or more of the following treatments for people with severe serotonin syndrome:

  • immediate withdrawal from the medication causing the reaction
  • medications that reduce serotonin levels
  • medications that reduce muscle stiffness or muscle spasms
  • intravenous (IV) fluids to improve hydration and reduce fever

Doctors can prevent serotonin syndrome by monitoring people taking high risk medications and prescribing treatments that have a low risk of interacting with a person’s current medications.

People can reduce their risk of developing serotonin syndrome by knowing their risk and staying informed.

Populations at risk for serotonin syndrome include people who recently started or increased the dose of a medication that increases serotonin levels. Additionally, those who take more than one prescription medication, herbal supplement, or illicit drug that increases serotonin levels are also at a higher risk.

People can speak with their doctors about the possible risks of developing serotonin syndrome. An individual should always inform their doctor about the medications and supplements they currently take. Doing this helps prevent potentially harmful drug interactions.

Some FAQs about serotonin syndrome may include:

What are the signs of serotonin syndrome?

Symptoms of serotonin syndrome can occur within minutes or hours of starting a new medication, or increasing the dose of an existing one. Symptoms can include agitation, dilated pupils, and twitching muscles. In more severe cases, symptoms can include loss of consciousness, coma, and seizures.

How long does serotonin syndrome last?

Usually, symptoms of serotonin syndrome will resolve within 1 to 2 days after stopping the causative medications. However, drugs with longer half-lives may cause symptoms to persist for longer.

Can sertraline cause serotonin syndrome?

Different drugs can potentially cause serotonin syndrome. This includes selective serotonin reuptake inhibitors (SSRIs) such as sertraline. Other types of antidepressants can also cause serotonin syndrome, as well as other types of drugs such as certain pain drugs, herbal supplements, and anti-nausea medications.

How to relieve serotonin syndrome?

Treating for serotonin syndrome will likely involve stopping or reducing the dose of the causative drug. A doctor may also recommend drugs to block serotonin production, such as cyproheptadine, or to reduce symptoms, such as benzodiazepines. They may also suggest intravenous fluids to improve hydration.

Serotonin syndrome occurs when a person takes one or more substances that cause high serotonin levels in the body. Substances that can cause serotonin syndrome include antidepressants, certain herbal supplements, and certain illicit drugs.

People who develop serotonin syndrome usually experience symptoms within 6 hours to a day of ingesting the causative substance.

People usually recover once they stop taking the medication that caused their symptoms. Serotonin syndrome can lead to a range of nonspecific symptoms, which makes it difficult to diagnose.

A person should contact their doctor if they experience any of the symptoms that healthcare professionals have associated with serotonin syndrome.