What are the symptoms of serotonin syndrome?

Symptoms of Serotonin Syndrome

Serotonin syndrome is characterized by a triad of mental status changes, autonomic instability, and neuromuscular hyperactivity, with the Hunter criteria requiring a patient to have taken a serotonergic drug within the past 5 weeks and exhibiting specific symptoms such as clonus, tremor, hyperreflexia, hypertonia, and hyperthermia. 1

Key Diagnostic Features (Hunter Criteria)

The Hunter criteria are considered the diagnostic standard for serotonin syndrome and include the following symptoms:

• Neuromuscular Abnormalities:

  • Spontaneous clonus
  • Inducible clonus
  • Ocular clonus
  • Tremor
  • Hyperreflexia
  • Hypertonia (muscle rigidity)

• Autonomic Dysfunction:

  • Hyperthermia (temperature >38°C)
  • Tachycardia
  • Diaphoresis (sweating)
  • Flushing
  • Hypertension

• Mental Status Changes:

  • Agitation
  • Confusion
  • Anxiety

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Symptom Severity Spectrum

Serotonin syndrome presents as a spectrum of severity:

1. Mild: Serotonergic features that may not concern the patient

   • Mild tremor
   • Slight hyperreflexia
   • Mild anxiety

2. Moderate: Significant distress requiring treatment (not life-threatening)

   • More pronounced tremor and hyperreflexia
   • Increased agitation
   • Diaphoresis
   • Mild temperature elevation

3. Severe: Medical emergency

   • Severe hyperthermia (can exceed 41°C)
   • Pronounced muscle rigidity
   • Multiple organ failure
   • Approximately 25% of severe cases require intubation and mechanical ventilation

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Common Pitfalls in Diagnosis

• Misdiagnosis: Serotonin syndrome is often confused with neuroleptic malignant syndrome, anticholinergic toxicity, or malignant hyperthermia 4

• Overlooked Diagnosis: The condition is frequently neglected due to general unawareness among physicians about the condition or drugs associated with it 4

• Relying on Outdated Criteria: Using Sternbach's criteria (which have low specificity) instead of the more specific Hunter criteria can lead to misdiagnosis 3

• Failure to Recognize Early Signs: Early recognition is critical as the syndrome can rapidly progress from mild to severe, potentially leading to rhabdomyolysis, renal failure, disseminated intravascular coagulation, seizures, and death (11% mortality rate without proper treatment) 1

Risk Factors

• Taking multiple serotonergic medications simultaneously (particularly high risk with MAOIs combined with any serotonergic drug) 1
• Recent medication changes or dose increases 4
• Genetic polymorphisms affecting serotonin metabolism 5

Clinical Implications

If not promptly recognized and treated, serotonin syndrome can lead to serious complications:

• Rhabdomyolysis
• Renal failure
• Disseminated intravascular coagulation
• Seizures
• Death (approximately 11% mortality rate without proper treatment)

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Early recognition of these symptoms is crucial for timely intervention, which includes discontinuation of serotonergic agents and supportive care, with benzodiazepines for agitation control and consideration of cyproheptadine for moderate to severe cases 1, 2.