What are the signs and symptoms of serotonin syndrome?

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From the Guidelines

Serotonin syndrome is a potentially life-threatening condition characterized by excessive serotonin activity in the brain and body, with the classic triad of symptoms including altered mental status, autonomic instability, and neuromuscular abnormalities, as described in the study by 1. The signs and symptoms of serotonin syndrome can be highly variable, but the most common clinical finding is myoclonus, which occurs in slightly more than half of cases, according to 1. Some key symptoms to look out for include:

  • Altered mental status (confusion, agitation, anxiety, hallucinations)
  • Autonomic instability (high fever, sweating, rapid heart rate, high blood pressure, dilated pupils, flushing)
  • Neuromuscular abnormalities (muscle rigidity, tremor, clonus, hyperreflexia, especially in the lower limbs)
  • Other common symptoms include shivering, diarrhea, headache, and difficulty with coordination. It's essential to note that symptoms typically develop rapidly, often within hours of taking a new serotonergic medication or increasing the dose of an existing one, as mentioned in 1. The severity of serotonin syndrome can range from mild to life-threatening, with severe cases potentially leading to seizures, respiratory failure, and death if not promptly treated, highlighting the importance of prompt recognition and discontinuation of the offending agents, as emphasized in 1.

From the Research

Signs and Symptoms of Serotonin Syndrome

The signs and symptoms of serotonin syndrome can be diverse and nonspecific, making diagnosis challenging. According to 2, serotonin syndrome classically consists of a triad of signs and symptoms broadly characterized as:

  • Alteration of mental status
  • Abnormalities of neuromuscular tone
  • Autonomic hyperactivity

Clinical Manifestations

As noted in 3, the syndrome is characterized by a constellation of symptoms, including:

  • Confusion
  • Fever
  • Shivering
  • Diaphoresis
  • Ataxia
  • Hyperreflexia
  • Myoclonus
  • Diarrhea

Spectrum of Toxicity

4 describes serotonin toxicity as a spectrum, ranging from mild to severe, with clinical manifestations that can include:

  • Neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity)
  • Autonomic stimulation (hyperthermia, tachycardia, diaphoresis, tremor, flushing)
  • Changed mental state (anxiety, agitation, confusion)

Diagnostic Criteria

As mentioned in 5, the diagnosis of serotonin syndrome is often based on the presence of at least three of Sternbach's 10 clinical features, although these features have low specificity. The Hunter Serotonin Toxicity Criteria use a smaller, more specific set of clinical features for diagnosis, including clonus.

Common Symptoms

6 lists common symptoms of serotonin syndrome, including:

  • Agitation
  • Confusion
  • Rapid heart rate
  • High blood pressure
  • Dilated pupils
  • Muscle rigidity
  • Tremors
  • Sweating
  • Diarrhea

These symptoms can occur when serotonergic medicines are taken alone or in combination, especially when a new medication is added or the dose of an existing medication is changed.

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

Serotonin toxicity: a practical approach to diagnosis and treatment.

The Medical journal of Australia, 2007

Research

Serotonin syndrome and drug combinations: focus on MAOI and RIMA.

European archives of psychiatry and clinical neuroscience, 1997

Research

Serotonin syndrome: An often-neglected medical emergency.

Journal of family & community medicine, 2024

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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