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What drugs can cause serotonin syndrome?

Medically reviewed by Kristianne Hannemann, PharmD. Last updated on June 9, 2025.

Official Answer by Drugs.com

Serotonin syndrome is a potentially life-threatening condition caused by an excess of serotonin in the body, usually triggered by medications or drugs that increase serotonin activity. It most commonly occurs when certain antidepressants, migraine medications, opioids, or illicit drugs are taken alone in high doses or, more often, in combination. Common drug classes that can cause serotonin syndrome include selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and opioids like tramadol.

What is Serotonin Syndrome?

Serotonin syndrome occurs when there is too much serotonin—a chemical messenger—in the central nervous system. This overload is typically due to medication interactions, overdose, or recent changes in drug therapy.

Symptoms of serotonin syndrome can range from mild to severe, and may include:

What Types of Drugs Can Cause Serotonin Syndrome?

Any drug that increases serotonin levels or activity in the brain can potentially cause serotonin syndrome, especially when combined with other serotonergic agents. These include:

What are High-Risk Drug Combinations?

Certain drug combinations significantly increase the risk of serotonin syndrome, particularly:

Polypharmacy (taking multiple serotonergic drugs) or recent changes in medication doses are major risk factors.

Can Over-the-Counter or Recreational Drugs Cause It?

Yes, both over-the-counter (OTC) medications and recreational drugs can cause serotonin syndrome, especially when combined with other substances that also increase serotonin levels.

Some examples include:

Summary Table: Common Drugs That Can Cause Serotonin Syndrome

Drug/Class Examples
SSRIs Fluoxetine, sertraline, citalopram
SNRIs Venlafaxine, duloxetine
TCAs Amitriptyline, clomipramine
MAOIs Phenelzine, tranylcypromine
Triptans Sumatriptan, rizatriptan
Opioids Tramadol, fentanyl, meperidine
Illicit drugs MDMA, LSD, cocaine, amphetamines
OTC/supplements Dextromethorphan, St. John’s Wort, 5-HTP
CNS stimulants Amphetamine, cocaine, methylphenidate, phentermine
Others Linezolid, lithium, buspirone, ondansetron

This is not a complete table of all medications that can cause serotonin syndrome. If you are taking medications that affect serotonin, always consult your healthcare provider before starting, stopping, or combining drugs or supplements.

How is Serotonin Syndrome Diagnosed and Treated?

Diagnosis is based on recognizing the pattern of symptoms and recent exposure to serotonergic drugs, as there is no specific laboratory test for serotonin syndrome.

Treatment involves:

When Should Someone Seek Medical Attention?

Seek immediate medical help if you or someone you know develops symptoms such as confusion, agitation, tremors, muscle stiffness, rapid heartbeat, or excessive sweating soon after starting or changing a serotonergic medication. Serotonin syndrome can progress quickly and may be fatal if not treated promptly.

References
  1. Merck Manual. n.d. Drugs That Can Cause Serotonin Syndrome. Accessed on June 8, 2025 at https://www.merckmanuals.com/professional/multimedia/table/drugs-that-can-cause-serotonin-syndrome
  2. Nadeem, Z., et. al. 2024. Serotonin syndrome and cannabis: A case report. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 32(1), 100–101. https://doi.org/10.1177/10398562231219858
  3. Simon, L. V., et. al. 2024. Serotonin Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Accessed on June 8, 2025 at https://www.ncbi.nlm.nih.gov/books/NBK482377/

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