What is serotonin syndrome?

What is Serotonin Syndrome?

Serotonin syndrome is a potentially life-threatening toxic condition caused by excessive serotonergic activity in the central nervous system, characterized by a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. 1, 2

Clinical Presentation

Serotonin syndrome manifests through three distinct categories of symptoms that occur together:

Mental Status Changes

• Patients present with agitated delirium, confusion, or altered consciousness ranging from mild confusion to coma in severe cases 2
• These changes develop rapidly, typically within 6-24 hours after starting or increasing a serotonergic medication 1, 2

Autonomic Hyperactivity

• Hyperthermia (elevated temperature up to 41.1°C) 2
• Tachycardia and tachypnea 2
• Hypertension or blood pressure fluctuations (≥20 mm Hg diastolic or ≥25 mm Hg systolic change within 24 hours) 2
• Diaphoresis and mydriasis 2

Neuromuscular Abnormalities

• Clonus (spontaneous, inducible, or ocular) and hyperreflexia are highly diagnostic features when occurring with serotonergic drug use 1, 2
• Myoclonus (present in 57% of cases) 3
• Muscle rigidity and tremor 2

Diagnostic Criteria

The American Academy of Pediatrics recommends using the Hunter Criteria for diagnosis, which requires the presence of a serotonergic agent plus one of the following 1, 2:

• Spontaneous clonus
• Inducible clonus with agitation or diaphoresis
• Ocular clonus with agitation or diaphoresis
• Tremor and hyperreflexia
• Hypertonia with temperature above 38°C and ocular or inducible clonus

There are no pathognomonic laboratory or radiographic findings for serotonin syndrome—diagnosis is purely clinical 2

Severity and Prognosis

Severity Classification

• Mild cases: May be easily missed due to variable presentation 2
• Moderate cases: Require hospitalization with continuous cardiac monitoring 1
• Severe cases: Medical emergency with rapid onset of severe hyperthermia (>41.1°C), muscle rigidity, and multiple organ failure 2

Mortality and Complications

• The mortality rate is approximately 11% 1, 2
• Approximately one-quarter of patients require intubation, mechanical ventilation, and ICU admission 1
• Complications include rhabdomyolysis with elevated creatine kinase, metabolic acidosis, elevated serum aminotransferase, renal failure, seizures, and disseminated intravascular coagulopathy 2

Causative Mechanisms

• Serotonin syndrome is non-idiosyncratic, meaning it is predictable and occurs with the addition of a new serotonergic drug, increased dosage of an existing drug, or addition of a second serotonergic agent 2, 3
• It results from excessive stimulation of central nervous system 5-HT1A and 5-HT2A receptors 4
• Can occur with a single standard therapeutic dose, drug interactions, excessive use, or intentional overdose 5

Important Diagnostic Pitfalls

Serotonin syndrome can be confused with several other conditions 1, 3:

• Neuroleptic malignant syndrome
• Malignant hyperthermia
• Anticholinergic syndrome
• Withdrawal syndromes
• Sepsis 6
• Decompensated hyperthyroidism 6

The key differentiating features are myoclonus and hyperreflexia, which are characteristic of serotonin syndrome 3