What are the signs and symptoms of serotonin syndrome?

Signs and Symptoms of Serotonin Syndrome

Serotonin syndrome is characterized by a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities that occur due to excessive serotonergic activity in the central nervous system. 1

Clinical Triad

Mental Status Changes

• Agitated delirium and confusion are common mental status changes 1
• Restlessness and altered mental status may progress to delirium 2

Autonomic Hyperactivity

• Elevated temperature (up to 41.1°C/106°F) 1
• Tachycardia and tachypnea 1
• Hypertension or blood pressure fluctuations 1, 3
• Diaphoresis (excessive sweating) 1
• Mydriasis (dilated pupils) 1, 2
• Diarrhea may occur 2

Neuromuscular Abnormalities

• Myoclonus (present in 57% of cases) - most characteristic finding 4
• Hyperreflexia - highly diagnostic when occurring with serotonergic drug use 1, 5
• Clonus (spontaneous, inducible, or ocular) - highly diagnostic 1, 5
• Muscle rigidity, especially in severe cases 1
• Tremor 1

Diagnostic Criteria (Hunter Criteria)

The American Academy of Pediatrics recommends using the Hunter Criteria for diagnosis, which require:

• Presence of a serotonergic agent plus one of the following: 5
  • Spontaneous clonus 1
  • Inducible clonus with agitation or diaphoresis 1
  • Ocular clonus with agitation or diaphoresis 1
  • Tremor and hyperreflexia 1
  • Hypertonia with temperature above 38°C (100.4°F) and ocular or inducible clonus 1

Severity Classification

Mild Serotonin Syndrome

• Mild tachycardia and hypertension 6
• Mydriasis 6
• Diaphoresis 6
• Shivering 6
• Tremor 6

Moderate Serotonin Syndrome

• Tachycardia and hypertension 6
• Hyperthermia (up to 40°C/104°F) 6
• Hyperactive bowel sounds with diarrhea 6
• Increased muscle tone with hyperreflexia 6
• Mild agitation or hypervigilance 6

Severe Serotonin Syndrome (Medical Emergency)

• Rapid onset of severe hyperthermia (>41.1°C/106°F) 1
• Severe muscle rigidity 1
• Multiple organ failure 1
• Potential complications include: 1, 5
  • Rhabdomyolysis with elevated creatine kinase
  • Metabolic acidosis
  • Elevated serum aminotransferase
  • Renal failure with elevated serum creatinine
  • Seizures
  • Disseminated intravascular coagulopathy

Important Clinical Considerations

• Symptoms typically develop within minutes to hours (usually 6-24 hours) after starting or increasing the dose of a serotonergic medication 1, 5
• The condition is non-idiosyncratic, meaning it can occur with the addition of a new drug, increased dosage of an existing drug, or addition of a second serotonergic drug 1, 4
• Approximately one-quarter of patients require intubation, mechanical ventilation, and ICU admission 5
• The mortality rate for serotonin syndrome is approximately 11% 1, 5
• There are no pathognomonic laboratory or radiographic findings for serotonin syndrome 1

Common Pitfalls in Diagnosis

• Serotonin syndrome can be confused with other conditions such as neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic syndrome, and withdrawal syndromes 5, 4
• The extremely variable presentation can make diagnosis challenging 3
• Clonus and hyperreflexia are the most reliable diagnostic features when they occur in the setting of serotonergic drug use 1, 5
• Many clinicians are unaware of the condition or drugs associated with it, leading to this potentially fatal condition being overlooked 2