Serotonin Syndrome

What is serotonin syndrome?

Serotonin syndrome is a potentially life-threatening drug reaction that results from having too much serotonin in your body. Serotonin is a neurotransmitter, a chemical produced by nerve cells in your brain and other areas of your body.

Most people can safely take serotonin-affecting (serotonergic) medication when it’s prescribed at the appropriate dosage and under the guidance of their healthcare provider. Serotonin syndrome happens most often when you either take a new drug or take an increased dose of a drug that increases the level of serotonin in your body. If your body processes serotonin differently or it can’t process an increased amount of serotonin, serotonin syndrome symptoms can happen.

Serotonin syndrome can cause mild symptoms (like diarrhea or nausea) to severe symptoms (like high fever or seizures). In some cases, severe serotonin syndrome can be fatal if not recognized and treated quickly.

Healthcare providers first recognized serotonin syndrome in the 1960s, after the approval of the first antidepressant medications. Today, more serotonin-affecting medications are available. This has led to a growing number of cases of serotonin syndrome.

Who gets serotonin syndrome?

Anyone who takes certain prescription medications, over-the-counter drugs, herbal or dietary supplements and illegal drugs that affect their body’s serotonin levels could be at risk for serotonin syndrome. It happens to people of any age.

What are the most common serotonin syndrome symptoms?

Symptoms of serotonin syndrome and their severity vary from person to person. They can be mild to severe to even fatal.

If you’re taking a medication that affects serotonin and experience any of the following symptoms, call your healthcare provider or visit an urgent or emergency care facility right away.

Mild symptoms

• Nervousness.
• Nausea, vomiting.
• Diarrhea.
• Dilated pupils.
• Tremor.

Moderate symptoms

• Agitation, restlessness.
• Muscle twitching, involuntary muscle contractions, muscle spasms, muscle rigidity.
• Sweating, shivering.
• Abnormal (side-to-side) eye movements.

Severe symptoms

• Confusion, disorientation, delirium.
• Rapid heart rate.
• High blood pressure.
• High body temperature (greater than 101.3 Fahrenheit [38.5 Celsius]).
• Seizures.
• Abnormal heartbeat.
• Passing out, fainting.

How quickly do symptoms of serotonin syndrome develop?

Symptoms usually begin within a few hours of taking a new medication that affects serotonin levels or increasing the dose of a drug you’re already taking. Nearly all people will experience symptoms within 24 hours of starting, adding or increasing the dosage of a serotonergic medication or product.

What causes serotonin syndrome?

A rise in serotonin levels in your body causes serotonin syndrome. This increase in serotonin can happen if you:

• Take more than one medication that affects serotonin levels.
• Recently started on a medication or increased the dose of a medication known to increase serotonin levels.
• Take too much of one serotonin-related medication, accidentally or on purpose.
• Use certain illegal drugs or herbal products or over-the-counter drugs that affect serotonin levels.

What medications and other products affect serotonin levels and could cause serotonin syndrome?

Antidepressants

Antidepressants are the most commonly used medications that affect serotonin levels. When involved in serotonin syndrome, they’re often used with other serotonergic drugs that treat other conditions; for example, triptan migraine drugs or opioid pain medications.

Antidepressant drug classes and medication examples that can increase serotonin levels include:

• Selective serotonin reuptake inhibitors (SSRIs): This class includes fluoxetine (Prozac®), citalopram (Celexa®), sertraline (Zoloft®), paroxetine (Paxil®) and escitalopram (Lexapro®). This drug class is the most common antidepressant class involved in serotonin syndrome due to its widespread use.
• Serotonin-norepinephrine reuptake inhibitors (SNRIs): This class includes duloxetine (Cymbalta®), venlafaxine (Effexor®), desvenlafaxine (Pristiq), levomilnacipran (Fetzima) and milnacipran (Savella).
• Tricyclic antidepressants: This class includes amitriptyline (Elavil®), clomipramine (Anafranil®), nortriptyline (Pamelor®), desipramine (Norpramin®), doxepin (Sinequan®), imipramine (Tofranil®) and trimipramine (Surmontil®).
• Monoamine oxidase inhibitors: This class includes phenelzine (Nardil®), selegiline (Emsam®) and tranylcypromine (Parnate®).
• Serotonin modulators: This class includes nefazodone and trazodone (Desyrel®).
• Norepinephrine reuptake inhibitor: This class includes bupropion (Wellbutrin®).

Other medications

Other medications can also affect your body’s serotonin level, especially when combined with other drugs that affect serotonin. These medications treat:

• Severe pain: Drugs in this category include opioids like tramadol (Ultram®), meperidine (Demerol®), tapentadol (Nucynta®), hydrocodone (Hysingla ER®), oxycodone (Oxyxontin®), fentanyl (Actiq®) and methadone.
• Coughing: Over-the-counter (OTC) cough and cold medications containing dextromethorphan can affect serotonin levels.
• Migraine headaches: Headache drugs in the triptan family include almotriptan (Axert®), eletriptan (Relpax®), frovatriptan (Frova®), rizatriptan (Maxalt®), sumatriptan (Imitrex®) and zolmitriptan (Zomig®).
• HIV/AIDS: Ritonavir (Norvir®).
• Antibiotic: Linezolid (Zyvox®).
• Anti-nausea medications: Metoclopramide (Reglan®), granisetron (Sustol®), droperidol (Inapsine®) and ondansetron (Zofran®).
• Mood stabilizer: Lithium (Lithobid®).

Other products

Other herbal and dietary supplements and illegal substances that affect serotonin levels and could cause serotonin syndrome include:

• Herbal supplements: These can include ginseng, St. John’s wort, Syrian rue and nutmeg.
• Illegal substances: These substances include ecstasy, LSD, cocaine, amphetamines and methamphetamines.
• Dietary supplement: Tryptophan.

Medical experts still have much to learn about serotonin syndrome. If you have concerns about the possible serotonin-affecting medications you take, talk to your healthcare provider or local pharmacist.

How do doctors diagnose serotonin syndrome?

There aren’t any tests to diagnose serotonin symptoms. Your healthcare provider usually makes the diagnosis based on the results of your physical exam, review of your symptoms and history of medications you take that affect serotonin levels.

You can assist your healthcare provider by telling them all the products you take, including prescription medicines, over-the-counter medicines, supplements, herbal products and illegal drugs. (Be honest. Don’t worry. Your healthcare provider is here to help you, not judge you.)

Your healthcare provider may order:

• Blood and urine tests to measure the levels of drugs you’re taking.
• Tests to check how well your body is functioning.
• Tests to look for signs of infection, including a spinal tap.
• Other tests (including chest X-ray, CT scan), as needed, to rule out other disorders that may cause similar symptoms or to identify any complications.

How is serotonin syndrome treated?

Your treatment depends on the severity of your symptoms.

• Mild symptoms: If your symptoms are mild, stopping the medication or changing your dose usually makes symptoms go away within 24 to 72 hours. If your symptoms aren’t going away quickly, you may be given a serotonin blocker, such as cyproheptadine (Periactin®).
• Moderate symptoms: If your symptoms are moderate, you may be observed in the hospital for at least 24 hours to make sure your symptoms are improving with treatment.
• Severe symptoms: If your symptoms are severe, you’ll be admitted to the intensive care unit (ICU), where your body and organ function can be closely monitored.

Treatments, depending on your symptoms, may include:

• A sedative, such as benzodiazepine, to relieve such symptoms as agitation, muscle stiffness and seizure-like movements.
• IV fluids to restore hydration and treat fever, and 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 Fahrenheit [41.1 Celsius]).
• Cyproheptadine, a serotonin-blocking agent, if other treatments aren’t working or aren’t working quickly enough.

If your case of serotonin syndrome was caused by an antidepressant, it may take several weeks for the medication to clear your body and for your symptoms to completely go away.

Don’t stop your medication or change your dose without talking to your healthcare provider first. However, if you have severe symptoms or your symptoms have worsened, seek emergency care. Serotonin syndrome can be life-threatening.

What are the complications of serotonin syndrome?

Without treatment, serotonin symptoms can cause:

• Seizures.
• Trouble breathing.
• Kidney failure. The breakdown products of muscle (from spasms) are released into your blood, which is filtered through your kidneys. If left untreated, these products can cause severe kidney damage.
• Coma.
• Death.

What can I do to prevent serotonin syndrome?

It’s important to keep close tabs on all medications you take. Read all warnings on your drug’s packaging or informational sheets. They’ll tell you if there’s a risk of serotonin syndrome. Don’t stop taking any medication before talking with your healthcare provider first. Keep all of your healthcare providers updated about all the prescription medications, over-the-counter drugs, herbs and supplements and illegal drugs you take.

If you take an antidepressant (especially SSRIs or SNRIs) along with a triptan medication for headaches, your doctor should closely monitor you. The risk is thought to be rare or perhaps non-existent, as different subtypes of the receptor are targeted. The American Migraine Foundation generally considers the combination safe, and it’s felt that the benefits outweigh the risks. But just remember, you have a role, too: Call your healthcare provider if you experience any of the symptoms listed in this article.

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.

What can I expect if I have serotonin syndrome?

If you’re quickly diagnosed and treated, most people who have serotonin syndrome will see their symptoms go away completely within 24 to 72 hours.

After recovery, your healthcare provider can:

• Lower the dose of the medication causing the increase in serotonin level to the lowest effective dose.
• Avoid prescribing two high-dose, serotonin-affecting medications.
• Change to different medication(s) that don’t affect serotonin.

When should I call 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 drug or increased the dose of a drug you’re currently taking and these drugs are known to affect serotonin levels.

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

A note from Cleveland Clinic

Be sure your healthcare provider — all of your healthcare providers — know all the medications and products you take. This includes prescription and over-the-counter medications, herbal and dietary supplements, and illegal drugs. Read the warning information and informational sheets that come with all of your medications. Learn the symptoms of serotonin syndrome. If you take antidepressants, be particularly aware of serotonin syndrome symptoms, as this is a common cause of the condition, especially when used with other medications that increase serotonin levels. If you have questions about your medications or symptoms, call your healthcare provider or pharmacist. If you notice symptoms or if your symptoms worsen, call your healthcare provider right away or go to an emergency room.