Signs of Serotonin Syndrome
Serotonin syndrome presents with a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, with clonus and hyperreflexia being the most diagnostic features. 1, 2
Clinical Triad
Mental Status Changes
- Agitated delirium is the most common presentation 2
- Confusion ranging from mild to severe 2
- Altered consciousness that can progress to coma in severe cases 2
- Anxiety and agitation 3
Autonomic Hyperactivity
- Hyperthermia (temperature up to 41.1°C or >38°C) 2, 4
- Tachycardia and tachypnea 2
- Diaphoresis (profuse sweating) 2, 3
- Hypertension or blood pressure fluctuations (≥20 mm Hg diastolic or ≥25 mm Hg systolic change within 24 hours) 2
- Mydriasis (dilated pupils) 2
- Flushing 3
Neuromuscular Abnormalities
- Clonus (spontaneous, inducible, or ocular) - highly diagnostic 1, 2
- Hyperreflexia - highly diagnostic 1, 2
- Myoclonus (present in 57% of cases) 4
- Muscle rigidity 2, 3
- Tremor 2, 3
Diagnostic Criteria (Hunter Criteria)
The American Academy of Pediatrics recommends using the Hunter Criteria, which require exposure to a serotonergic agent plus ONE of the following: 1, 4
- Spontaneous clonus 1
- Inducible clonus with agitation or diaphoresis 1
- Ocular clonus with agitation or diaphoresis 1
- Tremor and hyperreflexia 1
- Hypertonia with temperature >38°C and ocular or inducible clonus 1
Timing and Onset
Symptoms typically develop within 6-24 hours after starting, increasing the dose of, or adding a second serotonergic medication. 1, 2
Severity Classification
Severe Serotonin Syndrome (Medical Emergency)
- Rapid onset of severe hyperthermia (>41.1°C) 2
- Severe muscle rigidity 2
- Multiple organ failure 2
- Mortality rate approximately 11% 1, 4
Potential Complications
- Rhabdomyolysis with elevated creatine kinase 2
- Metabolic acidosis 2
- Renal failure with elevated serum creatinine 2
- Elevated serum aminotransferase 2
- Seizures 2
- Disseminated intravascular coagulopathy 2
Critical Pitfalls
The presentation is extremely variable, and mild cases are easily missed. 2 There are no pathognomonic laboratory or radiographic findings for serotonin syndrome. 2
Serotonin syndrome can be confused with neuroleptic malignant syndrome (NMS), but key differentiating features include: 4
- Serotonin syndrome: hyperreflexia and clonus with history of serotonergic agents 4
- NMS: lead pipe rigidity with history of antipsychotic use 2
Physical restraints should be avoided as they exacerbate isometric contractions, worsening hyperthermia and lactic acidosis. 1, 4