Serotonin Syndrome

Serotonin syndrome (also known as serotonin toxicity) is a potentially life-threatening condition where you have too much serotonin in your body. Serotonin is a neurotransmitter, a chemical your brain and other tissues naturally make. But certain medications (like antidepressants), supplements and substances can raise serotonin levels.

Serotonin syndrome can cause mild symptoms (like diarrhea or nausea) to severe symptoms (like high fever or seizures). In severe cases, if left untreated, serotonin syndrome can be fatal.

Most people can safely take serotonin-affecting (serotonergic) medication when it’s prescribed at the right dosage and under the guidance of their healthcare providers. This condition happens most often when starting a new medicine or increasing a previous medication’s dosage. If your body processes serotonin differently or if it can’t handle the extra amount, this condition can happen.

Being aware of your medications and potential interactions can help prevent serotonin syndrome. Get help right away if you develop symptoms.

Symptoms of serotonin syndrome

Serotonin syndrome symptoms range from mild to severe — and can be life-threatening.

Mild to moderate symptoms include:

• Nervousness
• Nausea and vomiting
• Diarrhea
• Dilated pupils
• Shakiness (tremor)
• Agitation and restlessness
• Muscle twitching, spasms and rigidity
• Sweating and shivering
• Abnormal (side-to-side) eye movements

Severe symptoms include:

• Confusion, disorientation and delirium
• Rapid heart rate
• High blood pressure
• High body temperature (greater than 101.3 degrees Fahrenheit, or 38.5 degrees Celsius)
• Seizures
• Abnormal heartbeat
• Fainting

If you have these symptoms, call your healthcare provider or go to the ER right away.

Serotonin syndrome causes

A rise in serotonin levels in your body causes serotonin syndrome. Serotonin toxicity can result from how serotonergic medications are used, including:

• Taking more than one medication
• Recently starting a medication or increasing the dose of an existing one
• Taking too much of one medication, accidentally or on purpose
• Using certain substances, herbal products or over-the-counter (OTC) medicines

Antidepressants are the most commonly used medications that affect serotonin levels. When they lead to serotonin syndrome, it’s often because you’ve taken another medication that affects these levels.

Other medications can also lead to this condition, especially when combined. They include:

• Opioids for intense pain
• OTC cough and cold medications containing dextromethorphan
• Triptans for migraine headaches (very low risk)
• Ritonavir for HIV/AIDS
• Linezolid (an antibiotic)
• Anti-nausea medications
• Lithium (a mood stabilizer)

Supplements and substances that can contribute to serotonin syndrome include:

• Herbal supplements, like ginseng, St. John’s wort, Syrian rue and nutmeg
• Substances, like ecstasy, LSD, cocaine, amphetamines and methamphetamines
• A dietary supplement called tryptophan

Complications of serotonin toxicity

Without treatment, serotonin syndrome can cause serious complications, including:

• Seizures
• Trouble breathing
• Kidney failure
• Coma
• Death

How doctors diagnose this condition

Tests can’t measure the level of serotonin in your body. So, your healthcare provider relies on a physical exam and review of your symptoms and medication list to make a diagnosis.

You can help your provider by telling them all the products you take, including prescription medicines, OTC medicines, supplements and substances (drugs). Be honest. Don’t worry — your healthcare provider is here to help, not to judge.

To help assess the severity of serotonin syndrome or to rule out other causes of your symptoms, your provider may suggest:

• Blood and pee tests to measure the levels of substances in your body
• Tests to look for signs of infection, including a spinal tap
• Other tests (like a chest X-ray or CT scan), as needed

How is it treated?

Treatment depends on the severity of your symptoms:

• Mild symptoms: Stopping the medication or changing the dose usually makes symptoms go away within 24 to 72 hours. If they don’t go away quickly, your healthcare provider may give you a serotonin blocker, like cyproheptadine (Periactin®).
• Moderate symptoms: You may need to stay in the hospital for at least 24 hours to make sure your symptoms improve with treatment.
• Severe symptoms: You get treatment in the intensive care unit (ICU). Your care team can closely monitor your body and organ function here.

Treatments, depending on your symptoms, may include:

• A sedative to relieve symptoms like agitation, muscle stiffness and seizure-like movements
• IV fluids to fix dehydration and fever
• Oxygen through a mask to improve oxygen levels in your blood
• Medications to control heart rate and blood pressure
• A breathing tube for mechanical ventilation, sedation and muscle paralysis to reduce extremely high fever (106 degrees F, or 41.1 degrees C)

Don’t stop your medication or change your dose without talking to your healthcare provider first. If you have severe symptoms or your symptoms have worsened, get emergency care.

Recovery time

With quick diagnosis and treatment, most people see their symptoms go away completely within 24 to 72 hours.

If an antidepressant was the cause, it may take several weeks for the medication to clear your body and for your symptoms to go away completely. This is because antidepressants stay in your system for a long time.

When should I see my healthcare provider?

If you have symptoms (or worsening symptoms) of serotonin syndrome, call your healthcare provider right away or go to an emergency room. Be especially watchful if you’ve started a new medicine or increased the dose of one you’re currently taking.

Don’t stop taking medications or change the dose without talking to your provider first.

What can I expect if I have serotonin syndrome?

Serotonin syndrome typically disappears rapidly and safely when quickly treated.

Once you’re better, your healthcare provider will go over the risks and benefits of resuming the medication(s) that caused serotonin toxicity. Your provider can:

• Lower the dose of the medication to the lowest effective dose
• Avoid prescribing two high-dose, serotonin-affecting medications
• Change to a different medication(or medications) that don’t affect serotonin

Can this be prevented?

These steps can help you prevent serotonin syndrome:

• Keep close tabs on all medications you take.
• Read all warnings on your medicine packaging or informational sheets. They’ll tell you if there’s a risk of serotonin syndrome.
• Keep all your healthcare providers updated about all the prescription and OTC medications, herbs and supplements, and substances you take.
• Seek treatment for substance use disorder.

Taking these precautions can help you and your healthcare team spot signs of serotonin syndrome early. Early identification may help you avoid more severe symptoms.