Serotonin syndrome

Date Updated: 01/22/2022

Overview

Serotonin syndrome is a serious drug reaction. It is caused by medications that build up high levels of serotonin in the body.

Serotonin is a chemical that the body produces naturally. It's needed for the nerve cells and brain to function. But too much serotonin causes signs and symptoms that can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever and seizures). Severe serotonin syndrome can cause death if not treated.

Serotonin syndrome can occur when you increase the dose of certain medications or start taking a new drug. It's most often caused by combining medications that contain serotonin, such as a migraine medication and an antidepressant. Some illicit drugs and dietary supplements are associated with serotonin syndrome.

Milder forms of serotonin syndrome may go away within a day or two of stopping the medications that cause symptoms and, sometimes, after taking drugs that block serotonin.

Symptoms

Serotonin syndrome symptoms usually occur within several hours of taking a new drug or increasing the dose of a drug you're already taking.

Signs and symptoms include:

Agitation or restlessness
Insomnia
Confusion
Rapid heart rate and high blood pressure
Dilated pupils
Loss of muscle coordination or twitching muscles
High blood pressure
Muscle rigidity
Heavy sweating
Diarrhea
Headache
Shivering
Goose bumps

Severe serotonin syndrome can be life-threatening. Signs include:

High fever
Tremor
Seizures
Irregular heartbeat
Unconsciousness

When to see a doctor

If you suspect you might have serotonin syndrome after starting a new drug or increasing the dose of a drug you're already taking, call your health care provider right away or go to the emergency room. If you have severe or rapidly worsening symptoms, seek emergency treatment immediately.

Causes

Excessive accumulation of serotonin in the body creates the symptoms of serotonin syndrome.

Typically, nerve cells in the brain and spinal cord produce serotonin that helps regulate attention, behavior and body temperature.

Other nerve cells in the body, primarily in the intestines, also produce serotonin. Serotonin plays a role in regulating the digestive process, blood flow and breathing.

Although it's possible that taking just one drug that increases serotonin levels can cause serotonin syndrome in some people, this condition occurs most often when people combine certain medications.

For example, serotonin syndrome may occur if you take an antidepressant with a migraine medication. It may also occur if you take an antidepressant with an opioid pain medication.

Another cause of serotonin syndrome is intentional overdose of antidepressant medications.

A number of over-the-counter and prescription drugs may be associated with serotonin syndrome, especially antidepressants. Illicit drugs and dietary supplements also may be associated with the condition.

The drugs and supplements that could potentially cause serotonin syndrome include:

Selective serotonin reuptake inhibitors (SSRIs), antidepressants such as citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), escitalopram (Lexapro), paroxetine (Paxil, Pexeva, Brisdelle) and sertraline (Zoloft)
Serotonin and norepinephrine reuptake inhibitors (SNRIs), antidepressants such as desvenlafaxine (Pristiq), levomilnacipran (Fetzima), milnacipran (Savella), duloxetine (Cymbalta, Drizalma Sprinkle) and venlafaxine (Effexor XR)
Bupropion (Zyban, Wellbutrin SR, Wellbutrin XL), an antidepressant and tobacco-addiction medication
Tricyclic antidepressants, such as amitriptyline and nortriptyline (Pamelor)
Monoamine oxidase inhibitors (MAOIs), antidepressants such as isocarboxazid (Marplan) and phenelzine (Nardil)
Anti-migraine medications, such as carbamazepine (Tegretol, Carbatrol, others), valproic acid and triptans, which include almotriptan, naratriptan (Amerge) and sumatriptan (Imitrex, Tosymra, others)
Pain medications, such as opioid pain medications including codeine, fentanyl (Duragesic, Abstral, others), hydrocodone (Hysingla ER), meperidine (Demerol), oxycodone (Oxycontin, Roxicodone, others) and tramadol (Ultram, ConZip)
Lithium (Lithobid), a mood stabilizer
Illicit drugs, including LSD, ecstasy, cocaine and amphetamines
Herbal supplements, including St. John's wort, ginseng and nutmeg
Over-the-counter cough and cold medications containing dextromethorphan (Delsym)
Anti-nausea medications such as granisetron (Sancuso, Sustol), metoclopramide (Reglan), droperidol (Inapsine) and ondansetron (Zofran)
Linezolid (Zyvox), an antibiotic
Ritonavir (Norvir), an anti-retroviral medication used to treat HIV

Risk factors

Some people are more likely to be affected by the drugs and supplements that cause serotonin syndrome than are others, but the condition can occur in anyone.

You're at increased risk of serotonin syndrome if:

You recently started taking or increased the dose of a medication known to increase serotonin levels
You take more than one drug known to increase serotonin levels
You take herbal supplements known to increase serotonin levels
You use an illicit drug known to increase serotonin levels

Complications

Serotonin syndrome generally doesn't cause any problems once serotonin levels are back to their original levels.

If left untreated, severe serotonin syndrome can lead to unconsciousness and death.

Prevention

Taking more than one serotonin-related medication or increasing your dose of a serotonin-related medication increases your risk of serotonin syndrome. Know what medications you take and share a complete list of your medications with your doctor or pharmacist.

Be sure to talk to your doctor if you or a family member has experienced symptoms after taking a medication.

Also talk to your doctor about possible risks. Don't stop taking any medications on your own. If your doctor prescribes a new medication, make sure he or she knows about all the other medications you're taking, especially if you receive prescriptions from more than one doctor.

If you and your doctor decide the benefits of combining certain serotonin-level-affecting drugs outweigh the risks, be alert to the possibility of serotonin syndrome.

Diagnosis

No single test can confirm a serotonin syndrome diagnosis. Your doctor will diagnose the condition by ruling out other possibilities.

Your doctor will likely begin by asking about your symptoms, medical history and any medications you're taking. Your doctor will also conduct a physical examination.

To make sure your symptoms are caused by serotonin syndrome and not due to another cause, your doctor may use tests to:

Measure levels of any drugs you're using
Check for signs of infection
Check body functions that may be affected by serotonin syndrome

A number of conditions can cause symptoms similar to those of serotonin syndrome. Minor symptoms can be caused by several conditions. Moderate and severe symptoms similar to those of serotonin syndrome could be caused by:

A serious reaction to certain medications, such as some anesthetics, antipsychotic drugs and other agents known to produce these severe reactions
An overdose of illicit drugs, antidepressant medications or other medications that increase serotonin levels
Damage associated with illicit drug use
Severe alcohol withdrawal

Your doctor may order additional tests to rule out other causes of your symptoms. Tests may include:

Blood and urine tests
Chest X-ray
CT scan
Spinal tap (lumbar puncture)

Treatment

Treatment of serotonin syndrome depends on the severity of your symptoms.

If your symptoms are minor, a visit to the doctor and stopping the medication causing the problem may be enough.
If you have symptoms that concern your doctor, you may need to go to the hospital. Your doctor may have you stay in the hospital for several hours to make sure your symptoms are improving.
If you have severe serotonin syndrome, you'll need intensive treatment in a hospital.

Depending on your symptoms, you may receive the following treatments:

Muscle relaxants. Benzodiazepines, such as diazepam (Valium, Diastat) or lorazepam (Ativan), can help control agitation, seizures and muscle stiffness.
Serotonin-production blocking agents. If other treatments aren't working, medications such as cyproheptadine can help by blocking serotonin production.
Oxygen and intravenous (IV) fluids. Breathing oxygen through a mask helps maintain oxygen levels in your blood, and IV fluids are used to treat dehydration and fever.
Drugs that control heart rate and blood pressure. These may include esmolol (Brevibloc) or nitroprusside (Nitropress) to reduce a high heart rate or high blood pressure.

If your blood pressure is too low, your doctor may give you phenylephrine (Vazculep) or epinephrine (Adrenalin, Epipen, others).
A breathing tube and machine and medication to paralyze your muscles. You may need this treatment if you have a high fever.

Milder forms of serotonin syndrome usually go away within 24 to 72 hours of stopping medications that increase serotonin. You may need to take medications to block the effects of serotonin already in your system.

However, symptoms of serotonin syndrome caused by some antidepressants could take several weeks to go away completely. These medications remain in your system longer than do other medications that can cause serotonin syndrome.

Preparing for an appointment

Because serotonin syndrome can be a life-threatening condition, seek emergency treatment if you have worsening or severe symptoms.

If your symptoms aren't severe, you're likely to start by seeing your family doctor or a general practitioner. Here's some information to help you get ready for your appointment and to know what to expect from your doctor.

What you can do

Be aware of any pre-appointment steps you need to take. When you make the appointment, be sure to ask if there's anything you need to do in advance, such as quitting any of the current medications or supplements you take.
Write down any symptoms you're experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.
Write down key personal information, including any major stresses or recent life changes.
Make a list of all medications, vitamins or supplements that you're taking.
Take a family member or friend along, if possible. Sometimes it can be difficult to absorb all the information provided to you during an appointment. Someone who accompanies you may remember something that you missed or forgot.
Write down questions to ask your doctor.

Preparing a list of questions will help you make the most of your time with your doctor. For symptoms you think may be caused by serotonin syndrome, some basic questions to ask your doctor include:

Is serotonin syndrome most likely causing my symptoms, or could it be something else?
Other than the most likely cause, what are other possible causes of my symptoms?
What kinds of tests do I need?
What is the best course of action?
What are the alternatives to the primary approach that you're suggesting?
I have other health conditions. How can I best manage them together?
Can I still take the medications I've been prescribed, or will I need to change them or change the dose?
Are there any restrictions that I need to follow, such as avoiding certain drugs or supplements?

Don't hesitate to ask any other questions you have.

What to expect from your doctor

Your doctor is likely to ask you a number of questions, such as:

When did you begin experiencing symptoms?
Have your symptoms been continuous or occasional?
How severe are your symptoms?
What prescription and over-the-counter medications do you take?
Do you use any illicit drugs?
Do you take any dietary supplements?