Serotonin Syndrome: Everything to Know

Medically Reviewed By Alexandra Perez, PharmD, MBA, BCGP

Serotonin syndrome is a drug reaction that occurs when you have high levels of serotonin. This can happen if you take medication that increases your serotonin levels, particularly if you combine medications. The condition is also known as serotonin toxicity. High levels of serotonin can cause excessive stimulation of the central nervous system and peripheral serotonin receptors. However, the condition is not widely recognized amongst clinicians, and they may underdiagnose it due to symptoms being varied.

Read on to learn more about serotonin syndrome. This guide includes information about symptoms, causes, treatments, and diagnosis.

Key Facts About Serotonin Syndrome

  • Serotonin syndrome occurs when you have too much serotonin in your body.
  • This can happen if you take medications such as SSRIs and SNRIs. One medication or combined medications can cause serotonin syndrome.
  • Symptoms can vary and result in underdiagnosis. Common symptoms include agitation, confusion, and muscle twitching.
  • Cannabis and some foods, such as tuna, pork, and spinach, may contribute to the risks of serotonin syndrome.

Read the full article to learn more about serotonin syndrome.

What is serotonin?

Serotonin is a neurotransmitter, which means that it carries signals between the nerve cells in your brain. It can influence your emotions, mood, and sleep.

The reuptake of serotonin occurs when the nerve cells reabsorb it. However, if you take medications such as selective serotonin reuptake inhibitors (SSRIs), which are typically prescribed for depression, they block this reuptake, increasing serotonin activity.

This can cause excess serotonin, which may result in serotonin syndrome. Other names for serotonin syndrome include:

  • serotonin sickness
  • serotonin poisoning
  • serotonin storm
  • serotonergic syndrome
  • hyperserotonemia

What are the symptoms of serotonin syndrome?

Person with eyes closed and hand on head
Yana Bulgakova/Stocksy United

Although serotonin syndrome is uncommon, side effects can be dangerous. Symptoms can appear within hours of taking the medication, and they can worsen if you continue to take the medication.

If you have raised serotonin levels, you may experience:

Symptoms of severe serotonin syndrome include:

Seek immediate medical help if you or another person experiences any of these symptoms.

How do you treat serotonin syndrome?

Treatments will depend on whether you are experiencing mild or severe symptoms of serotonin syndrome.

Mild serotonin syndrome

Treatment for mild to moderate serotonin syndrome typically involves stopping the medications that increased serotonin levels. Following this, symptoms should improve within 1–3 days.

Severe serotonin syndrome

Your doctor may treat symptoms of severe serotonin syndrome with oral diazepam.

Benzodiazepines can also help with agitation, muscle rigidity, hyperactivity, and seizures. In extreme cases of excess muscle activity, muscle paralysis may be necessary.

If your body temperature is over 104°F (40°C), it is essential to cool down your core temperature. Prolonged fever can increase the risk of multi-organ failure or death. Cooling methods include ice packs and cooled fluids.

Severe, untreated serotonin syndrome may result in:

What causes serotonin syndrome?

Serotonin syndrome typically occurs as a result of taking medications that raise serotonin levels. This may be just one medication or a combination, including SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Medications that can cause serotonin syndrome include:

  • SNRI, SSRI, and tricyclic antidepressants
  • monoamine oxidase inhibitors
  • bupropion
  • antimigraine medications
  • prescription pain medications, such as codeine, oxycodone, fentanyl, and tramadol
  • lithium
  • illegal drugs, such as LSD, ecstasy, cocaine, and amphetamines
  • herbal supplements, such as St. John’s wort, ginseng, and nutmeg
  • dextromethorphan, which can be found in over-the-counter (OTC) cough and cold medications
  • antiemetics, such as granisetron, metoclopramide, ondansetron
  • linezolid
  • ritonavir

Learn more about medications commonly prescribed for depression.

Can food cause serotonin syndrome?

It is possible Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source that histamine can stimulate serotonin. Taking linezolid or ritonavir can inhibit your body’s ability to break down histamine.

Consuming excess amounts of high-histamine food can result in serotonin syndrome. Histamine-rich foods include:

  • fish such as tuna, mackerel, and Pacific saury
  • pork
  • chicken
  • spinach
  • soybean paste
  • red pepper paste
  • fermented foods, such as cabbage, radish, or yogurt
  • some condiments, such as mayonnaise and ketchup
  • cheese
  • alcoholic beverages, such as wine or beer

Chocolate also contains small amounts of serotonin. In large quantities, particularly alongside serotonin-inhibiting medications, chocolate can increase your risk of serotonin syndrome.

Can cannabis cause serotonin syndrome?

Tetrahydrocannabinol (THC) is the main component Trusted Source National Cancer Institute Governmental authority Go to source in cannabinoids, including cannabis, that affects your mental state. It is possible that THC can inhibit serotonin reuptake and activate serotonin receptors.

This means that using cannabis may result in serotonin syndrome. However, there are similarities between Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source the symptoms of serotonin syndrome and cannabis toxicity. It is important to consider both diagnoses if you have inhaled highly potent cannabis.

Find out more about how cannabis can affect your health.

How do you diagnose serotonin syndrome?

Diagnosing serotonin syndrome can be difficult due to the varying symptoms and similarities with other conditions. However, it is possible to follow the Hunter or Sternbach criteria to reach a diagnosis.

Hunter criteria

Clinicians typically use the Hunter Serotonin Toxicity Criteria to reach a diagnosis.

The Hunter Serotonin Toxicity Criteria specifies that, alongside the intake of a known serotonergic agent, one of the following must be present:

  • tremor and hyperreflexia
  • spontaneous clonus, or involuntary muscle contractions
  • muscle contractions that a clinician can induce, accompanied by agitation or heavy sweating
  • roving eye movements, with agitation or heavy sweating
  • hypertonia, or too much muscle tone
  • ocular or inducible clonus
  • temperature above 100.4°F (38°C)

Sternbach criteria

The Sternbach criteria for serotonin syndrome require that you have exposure to a serotonergic agent, alongside three or more of the following symptoms:

How rare is serotonin syndrome?

Because serotonin syndrome often goes undiagnosed, it is not possible to know exactly how many people it affects. However, researchers estimate that around 15% of people who take an excess of SSRIs will display symptoms of serotonin syndrome.

Antidepressant use among adults in the United States is increasing. Around 6% of adults took medication for depression in 1999, which rose to 10% by 2010. This further increased to 13.2% Trusted Source Centers for Disease Control and Prevention (CDC) Governmental authority Go to source between 2015–2018.

This increase in the use of antidepressants also increases the risks of serotonin syndrome.

Learn more about depression.

What is the outlook for serotonin syndrome?

If a doctor diagnoses serotonin syndrome early, there is a strong chance that you will recover within a few days. Confusion may persist for a number of days, though you may experience muscle pain for longer.

Can I prevent serotonin syndrome?

One way to prevent Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source or reduce the risk of serotonin syndrome is to make sure that your doctor or pharmacist is aware of all of the medications you take. They will be able to ensure that you do not take too much medication that inhibits serotonin.

Avoiding foods high in histamine can also help to reduce your risk of serotonin. This is particularly important if you take medicines such as linezolid and ritonavir.

Summary

Serotonin syndrome occurs when you have high levels of serotonin. This tends to occur when you take one or more serotonin-inhibiting medications or antidepressants. However, inhaling cannabinoids or eating foods high in histamine can also increase the risks of the condition.

Symptoms of serotonin syndrome can vary and are often similar to other conditions or toxicities. As such, serotonin syndrome may often go undiagnosed.

Contact your doctor if you experience symptoms of serotonin syndrome. It is important to make sure your prescriptions and OTC medications do not severely increase your serotonin levels.

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Medical Reviewer: Alexandra Perez, PharmD, MBA, BCGP
Last Review Date: 2022 Apr 29
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