What are the signs and effects of Serotonin (5-hydroxytryptamine) Syndrome?

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Last updated: May 28, 2025View editorial policy

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From the Guidelines

Serotonin syndrome is a life-threatening condition that requires immediate medical attention, characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, and can be triggered by combining serotonergic medications, such as SSRIs, SNRIs, MAOIs, triptans, and certain antibiotics or illicit drugs. The signs and effects of serotonin syndrome typically develop rapidly, often within hours of taking medications that increase serotonin levels. Common symptoms include:

  • Mental status changes (agitation, confusion, hallucinations)
  • Autonomic instability (high fever, sweating, rapid heart rate, high blood pressure, dilated pupils)
  • Neuromuscular abnormalities (muscle rigidity, tremors, hyperreflexia, clonus, and myoclonus) In severe cases, patients may experience seizures, respiratory failure, or even death 1.

The clinical presentation of serotonin syndrome can be extremely variable, making diagnosis challenging 1. The Hunter criteria are commonly used to diagnose serotonin syndrome, which includes symptoms such as tremor and hyperreflexia, spontaneous clonus, muscle rigidity, and temperature greater than 38°C 1.

Treatment of serotonin syndrome typically involves discontinuing the precipitating agent, providing supportive care, and administering benzodiazepines for agitation 1. In severe cases, serotonin antagonists like cyproheptadine may be used, with a pediatric dosage of 0.25 mg/kg per day 1. It is essential to seek emergency medical attention if serotonin syndrome is suspected, as prompt treatment can help prevent serious complications and improve outcomes 1.

The condition occurs because excessive serotonin overstimulates receptors in the brain and spinal cord, disrupting normal neurotransmitter function and causing this characteristic constellation of symptoms 1. Monoamine oxidase inhibitors (MAOIs) play a significant role in most cases of serotonin syndrome and should be avoided in combination with any other serotonergic drug 1.

In real-life clinical practice, it is crucial to exercise caution when combining two or more non-MAOI serotonergic drugs, including antidepressants, opioids, stimulants, and cough/cold/allergy medications 1. By being aware of the signs and effects of serotonin syndrome and taking prompt action, healthcare providers can help prevent this potentially life-threatening condition and improve patient outcomes.

From the Research

Signs of Serotonin Syndrome

  • Alteration of mental status 2, 3, 4, 5, 6
  • Abnormalities of neuromuscular tone, such as tremor, hyperreflexia, or myoclonus 2, 3, 4, 5, 6
  • Autonomic hyperactivity 2, 3, 4, 5, 6
  • Neuromuscular excitation 3, 6
  • Autonomic dysfunction 3, 6
  • Altered mental status 3, 6

Effects of Serotonin Syndrome

  • Potentially life-threatening toxic state 2, 3, 5, 6
  • Range in severity from mild to life-threatening 2
  • Can lead to significant morbidity and mortality if not recognized and treated promptly 5, 6
  • May lead to misdiagnosis due to diverse and nonspecific clinical manifestations 2
  • Requires prompt recognition and supportive care to prevent severe cases 2, 6

Management of Serotonin Syndrome

  • Withdrawal of the offending agent(s) 2, 3
  • Aggressive supportive care to treat hyperthermia and autonomic dysfunction 2
  • Administration of serotonin antagonists, such as cyproheptadine or chlorpromazine 2, 4
  • Inpatient hospitalization for moderate and severe cases 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Overview of serotonin syndrome.

Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 2012

Research

Treatment of the serotonin syndrome with cyproheptadine.

The Journal of emergency medicine, 1998

Research

Serotonin syndrome.

Ochsner journal, 2013

Research

Serotonin syndrome-A focused review.

Basic & clinical pharmacology & toxicology, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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