Serotonin syndrome (SS) is a potentially life-threatening drug reaction. It causes the body to have too much serotonin, a chemical produced by some nerve cells.

Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome

SS most often occurs when two or more medicines or drugs that affect the body's level of serotonin are taken together at the same time. The medicines cause too much serotonin to be released or to remain in the brain area.

For example, you can develop this syndrome if you take migraine medicines called triptans together with antidepressants called selective serotonin reuptake inhibitors (SSRIs), or selective serotonin/norepinephrine reuptake inhibitors (SSNRIs).

Common SSRIs include:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Sertraline (Zoloft)

SSNRIs include:

• Desvenlafaxine (Pristiq)
• Duloxetine (Cymbalta)
• Levomilnacipran (Fetzima)
• Milnacipran (Savella)
• Venlafaxine (Effexor)

Common triptans include:

• Almotriptan (Axert)
• Eletriptan (Relpax)
• Frovatriptan (Frova)
• Naratriptan (Amerge)
• Rizatriptan (Maxalt)
• Sumatriptan (Imitrex)
• Zolmitriptan (Zomig)

If you take these medicines, be sure to read the warning on the packaging. It tells you about the potential risk of SS. However, do not stop taking your medicine. Talk to your health care provider about your concerns first.

SS is more likely to occur when you first start taking or increase the dose of the medicine..

Older antidepressants called monoamine oxidase inhibitors (MAOIs) can also cause SS when combined with the medicines described above, as well as meperidine (Demerol, a painkiller), fentanyl, dextromethorphan (cough medicine), and others.

Street drugs, such as methamphetamine or other amphetamines, cocaine, opiates, ecstasy, LSD, and others have also been associated with SS.

Symptoms occur within minutes to hours of taking medicines that can cause SS, and may include:

• Agitation or restlessness
• Abnormal eye movements
• Diarrhea
• Fast heartbeat and high blood pressure
• Hallucinations
• Increased body temperature
• Loss of coordination
• Nausea and vomiting
• Overactive reflexes
• Rapid changes in blood pressure

People with SS will usually stay in the hospital for at least 24 hours for close observation.

Treatment may include:

• Benzodiazepine medicines to decrease agitation, seizure-like movements, and muscle stiffness
• Cyproheptadine (Periactin), a drug that blocks serotonin production
• Intravenous (through the vein) fluids
• Stopping medicines that caused the syndrome

In life-threatening cases, medicines that keep the muscles still (paralyze them), and a temporary breathing tube and breathing machine will be needed to prevent further muscle damage.

People may get slowly worse and can become severely ill if not quickly treated. Untreated, SS can be deadly. With treatment, symptoms usually go away in less than 24 hours. Permanent organ damage may result, even with treatment.

Uncontrolled muscle spasms can cause severe muscle breakdown. The products produced when the muscles break down are released into the blood and eventually go through the kidneys. This can cause severe kidney damage if not recognized and treated properly.

Contact your provider right away if you have symptoms of SS.

Always tell your providers which medicines you take. People who take triptans with SSRIs or SSNRIs should be closely followed, especially right after starting a medicine or increasing its dosage.

Published Date: April 03, 2024
Published By: Jesse Borke, MD, CPE, FAAEM, FACEP, Attending Physician at Kaiser Permanente, Orange County, CA. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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