Depression

What Is Serotonin Syndrome? Symptoms, Causes, Diagnosis, Treatment, and Prevention

Julie Lynn Marks
By
Chester Wu, MD
by

Serotonin syndrome is a rare but serious reaction that can happen when certain medications you’re taking cause too much serotonin to build up in your brain.

Colloquially known as the “feel-good” chemical, serotonin is a neurotransmitter that supports many of your body’s functions, including mood regulation, according to the Cleveland Clinic. Low levels of serotonin are thought to play a key role in the development of mental health conditions, such as depression and anxiety.

Serotonin syndrome most often happens when mixing medicines that contain serotonin, per Mayo Clinic. Common culprits are antidepressants, migraine treatments, dietary supplements, and illicit drugs.

“Since there are many over-the-counter and prescription medications that affect serotonin levels in our bodies, people may unintentionally and unknowingly develop serotonin syndrome after taking normal doses of these medications in combination,” explains Kelly Johnson-Arbor, MD, a medical toxicologist and co-medical director and interim executive director at the National Capital Poison Center in Washington, DC.

Symptoms of serotonin syndrome can range from mild to life-threatening, Mayo Clinic states. An accurate diagnosis is important so that you can stop taking the medicines that are causing the reaction and start any necessary treatments for serotonin syndrome.

“Early recognition of serotonin syndrome can prevent significant morbidity and mortality,” says Alan David Kaye, MD, PhD, a clinical professor in the department of anesthesiology and pharmacology, toxicology, and neurosciences at Louisiana State University School of Medicine in Shreveport.

Common Questions & Answers

What are common causes of serotonin syndrome?
The most common causes of serotonin syndrome include taking multiple medicines at once that affect your serotonin levels, taking an increased dose of a medication that affects serotonin, or using over-the-counter substances that affect serotonin levels.
How do you know if you have serotonin syndrome?
A healthcare provider can determine if you have serotonin syndrome. Common symptoms include heavy sweating, confusion, high blood pressure, rapid heart rate, twitching muscles, dilated pupils, diarrhea, headache, and shivering, among others.
How quickly does serotonin syndrome go away?
In some cases, serotonin syndrome can go away within 24 hours. In others, especially if antidepressants are the cause, it can take a few weeks to fully recover.

Signs and Symptoms of Serotonin Syndrome

Symptoms of serotonin syndrome can begin within minutes to hours of taking medications that affect your body’s serotonin levels, according to MedlinePlus.

“The presentation of serotonin syndrome is extremely variable, ranging from mild symptoms to a life-threatening syndrome,” says Dr. Kaye.

According to Mayo Clinic, symptoms may include:

  • A rapid heartbeat
  • High blood pressure
  • Restlessness or agitation
  • Confusion
  • Dilated pupils
  • Twitching muscles, rigid muscles, or a loss of muscle coordination
  • Copious sweating
  • Diarrhea
  • Shivering or goosebumps
  • Headache

Symptoms that may signal a severe or life-threatening reaction, per Mayo Clinic, include:

Causes and Risk Factors of Serotonin Syndrome

Serotonin syndrome is caused by medicines that allow too much serotonin to stay or be released in the brain, according to MedlinePlus.

“Anyone who takes medications that affect serotonin activity in the body is at risk for developing serotonin syndrome,” says Dr. Johnson-Arbor. “Serotonin syndrome can affect individuals of all ages.”

Though it’s possible to develop serotonin syndrome after taking just one medicine that increases serotonin levels, per Cleveland Clinic, it’s more likely to happen if you:

  • Combine medicines that influence serotonin levels in the body.
  • Start a new medication or up the dose of a current medication that raises serotonin levels.
  • Take too much of a medication that boosts serotonin levels.
  • Use herbal products, over-the-counter medicines, or illegal drugs that affect serotonin levels.

Medications That Could Cause Serotonin Syndrome

Medicines and products that affect serotonin levels in the body and could lead to serotonin syndrome in some cases, per Cleveland Clinic, include:

How Is Serotonin Syndrome Diagnosed?

“No single diagnostic test can confirm this syndrome,” notes Kaye. “Therefore, a diagnosis of serotonin syndrome is entirely clinical and is based on the history and physical examination, along with history of the patient’s use of [serotonin-containing] drugs.”

To be diagnosed with serotonin syndrome, you must have at least three of the following symptoms after taking at least one drug that affects serotonin levels, according to MedlinePlus:

  • Agitation
  • Heavy sweating
  • Fever
  • Abnormal eye movements
  • Mental changes, such as becoming confused
  • Muscle spasms
  • Shivering
  • Tremors
  • Uncoordinated movements
  • Overactive reflexes

Making a diagnosis is sometimes difficult, as symptoms of serotonin syndrome can be mild or mimic those of other conditions, like certain infections, heat stroke, or a drug overdose, says Kaye. “Because of the widespread use of serotonergic drugs, clinicians must maintain a high clinical suspicion for serotonin syndrome,” explains Kaye.

To make the right diagnosis and exclude other possible causes of your symptoms, doctors may run some tests, per Mayo Clinic, such as:

  • Chest X-rays
  • Blood or urine samples
  • A computed tomography (CT) scan
  • A spinal tap or lumbar puncture

Prognosis of Serotonin Syndrome

“The prognosis of serotonin syndrome is favorable if the patient is treated; therefore, physicians must be astute and aware of the possibility of this life-threatening syndrome,” says Kaye.

Duration of Serotonin Syndrome

With treatment, symptoms of serotonin syndrome usually go away in less than 24 hours, states MedlinePlus. However, if your serotonin syndrome was caused by antidepressants, it could take several weeks before the medications clear from your body and your symptoms go away, per the Cleveland Clinic.

How Is Serotonin Syndrome Treated?

People with serotonin syndrome usually need to stay in the hospital for at least a day so doctors can keep an eye on them, according to MedlinePlus. In many cases, serotonin syndrome can be treated simply by stopping the medications that are causing too much serotonin build-up in the brain, Johnson-Arbor says.

For certain symptoms of serotonin syndrome, per MedlinePlus, treatments may include:

  • IV fluids
  • Benzodiazepines, such as diazepam (Valium) or lorazepam (Ativan) to relieve muscle stiffness, seizures, or agitation
  • A serotonin-blocking medication, such as cyproheptadine (Periactin)
  • A temporary breathing tube to prevent muscle damage
  • Medicines that keep your muscles still (like vecuronium)

If you think you have symptoms of serotonin syndrome, you should call your doctor right away or go to the emergency room. Johnson-Arbor also recommends contacting poison control at 800-222-1222 or www.poison.org with any questions or concerns you have. “Both options [for contacting poison control] are free, confidential, and available 24 hours a day,” she adds.

Complications of Serotonin Syndrome

If serotonin syndrome goes untreated, per the Cleveland Clinic, it could lead to complications such as:

  • Seizures
  • Breathing difficulties
  • Coma
  • Death

The abnormal muscle movements and muscle stiffness associated with serotonin syndrome can lead to a complication called rhabdomyolysis, adds Johnson-Arbor. “Rhabdomyolysis occurs when damaged muscles break down, leaking their contents into the bloodstream,” Johnson-Arbor explains. “In some cases, rhabdomyolysis can result in kidney damage.”

Prevention of Serotonin Syndrome

You can prevent serotonin syndrome by keeping a close watch on all the medications you take and telling your provider about all medicines, supplements, or other substances you use, according to MedlinePlus.

“The best way to prevent this syndrome is to avoid multidrug regimens and to discontinue any [serotonin-containing] agent before starting another,” says Kaye.

“Because people often seek care from multiple different physicians and may get medications from multiple pharmacies, your doctor or pharmacist may not know every medication that you are taking unless you tell them,” adds Johnson-Arbor.

Don’t abruptly stop taking any medicines you’re taking without first talking with your doctor, per Mayo Clinic.

Research and Statistics: How Many People Have Serotonin Syndrome?

Serotonin syndrome is a rare condition, according to a review published in 2018 in Canadian Family Physician.

The true number of people who develop serotonin syndrome isn’t known, according to research.

One reason is that milder cases of serotonin syndrome may be under-reported, underdiagnosed, or misdiagnosed. “The number of actual cases is likely much greater than the actual reported cases,” says Kaye.

Related Conditions

Other conditions that could resemble serotonin syndrome, Kaye says, include:

  • Neuroleptic malignant syndrome (NMS) is a life-threatening neurological disorder caused by a bad reaction to antipsychotic or neuroleptic medicines, per the National Institutes of Neurological Disorders and Stroke.
  • Malignant hyperthermia is a genetic disease that causes a severe reaction to some kinds of anesthesia, according to Cleveland Clinic.
  • Anticholinergic toxicity can happen if the body is exposed to too much anticholinergic medications (such as antidepressants, antihistamines, or Parkinson’s disease medicines). The most common type of anticholinergic drug overdose is caused by antihistamines, research shows.
  • Antidepressant discontinuation syndrome affects about 20 percent of people who suddenly stop or reduce their dose of antidepressants after using them for at least a month. It includes developing unwanted symptoms, such as flu-like symptoms, insomnia, or electric shock-like sensations, according to studies.
  • Drug or alcohol withdrawal
  • Drug overdose
  • Infections, such as those related to meningitis or encephalitis
  • Heat stroke
  • Central hyperthermia is an abnormally high body temperature that’s common among people with a brain injury, according to research.

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