What are the symptoms of serotonin syndrome (SS) due to excessive levels of serotonin?

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Last updated: March 19, 2025View editorial policy

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From the Guidelines

Serotonin syndrome is a life-threatening condition characterized by excessive serotonin levels, requiring immediate medical attention, and its symptoms include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremors, excessive sweating, diarrhea, headache, and in severe cases, seizures and high fever. The symptoms of serotonin syndrome (SS) due to excessive levels of serotonin can be identified using the Hunter criteria, which is the most commonly used diagnostic criteria 1. According to the criteria, the symptoms of SS can be categorized into several groups, including:

  • Mental status changes: agitation, confusion, and altered mental status
  • Autonomic dysfunction: hypertension, tachycardia, tachypnea, and hyperthermia
  • Neuromuscular abnormalities: muscle rigidity, tremors, and clonus
  • Gastrointestinal symptoms: diarrhea and hyperactive bowel sounds

The treatment of SS involves discontinuing the precipitating agent and providing supportive care, which may include benzodiazepines for agitation, cooling measures for hyperthermia, and in severe cases, serotonin antagonists like cyproheptadine 1. The dosage of cyproheptadine is typically 12 to 24 mg over 24 hours, starting with 12 mg, followed by 2 mg every 2 hours for continuing symptoms, and a maintenance dose of 8 mg every 6 hours, given orally 1. It is essential to note that the mortality rate associated with SS is approximately 11%, with significant morbidity and mortality, and severe cases can be characterized by rhabdomyolysis, metabolic acidosis, elevated serum aminotransferase, renal failure, seizures, and disseminated intravascular coagulopathy 1.

The diagnosis of SS is primarily clinical, and there are no pathognomonic laboratory or radiographic findings 1. However, laboratory tests such as complete blood cell count, electrolytes, serum urea nitrogen, creatinine, arterial blood gas, hepatic transaminases, creatine kinase, urinalysis, toxicology screens, coagulation studies, electrocardiography, EEG, and brain imaging studies may be obtained based on clinical suspicion 1.

In terms of prevention, it is crucial to maintain an updated medication list and inform all healthcare providers about all medications, including supplements and over-the-counter drugs, as many combinations can unexpectedly increase serotonin levels 1.

From the Research

Symptoms of Serotonin Syndrome

The symptoms of serotonin syndrome (SS) due to excessive levels of serotonin include:

  • Restlessness 2
  • Hyperthermia 3, 2, 4
  • Tachycardia 3, 2, 4
  • Mydriasis 2
  • Increased tone 3, 2, 4
  • Agitation 2
  • Seizure-like activity 2
  • Roving eye movement 2
  • Dystonia 2
  • Acute consciousness disturbance 3
  • Rigidity 3
  • Spontaneous clonus in lower limbs 3
  • Autonomic dysregulation 4
  • Muscle rigidity 5
  • Horizontal ocular clonus 5
  • Confusion 5
  • Diaphoresis 5

Complications of Serotonin Syndrome

Serotonin syndrome can be complicated by:

  • Rhabdomyolysis 3
  • Acute renal failure 3
  • Acute pulmonary edema 3
  • Torsades des pointes (TdP) 4
  • Pulseless, wide complex tachycardia 4
  • Cardiovascular instability 4

References

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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