Serotonin Syndrome Symptoms
Serotonin syndrome presents with a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities that typically develop within 6-24 hours of starting or increasing a serotonergic medication. 1
Mental Status Changes
The neuropsychiatric manifestations include:
- Agitated delirium (most common presentation) 1
- Confusion 1
- Altered consciousness ranging from mild confusion to coma in severe cases 2, 3
Autonomic Hyperactivity
The autonomic symptoms are often the most dramatic and include:
- Hyperthermia (temperature up to 41.1°C or >106°F in severe cases) 1
- Tachycardia (heart rate increase ≥25% above baseline) 1
- Tachypnea (respiratory rate ≥50% above baseline) 1
- Hypertension or blood pressure fluctuations (≥20 mm Hg diastolic or ≥25 mm Hg systolic change within 24 hours) 2
- Diaphoresis (profuse sweating) 1, 4
- Mydriasis (dilated pupils) 1, 5
- Diarrhea 5, 6
Neuromuscular Abnormalities
These are the most diagnostically specific features:
- Clonus (spontaneous, inducible, or ocular) - highly diagnostic when present 1, 7
- Hyperreflexia - considered highly diagnostic in the setting of serotonergic drug use 1, 7
- Myoclonus (present in 57% of cases) 8
- Tremor 1, 4
- Muscle rigidity (particularly in severe cases) 1, 3
- Ataxia 6
Diagnostic Criteria to Recognize
The American Academy of Pediatrics recommends using the Hunter Criteria for diagnosis, which requires exposure to a serotonergic agent PLUS one of the following: 1, 7
- Spontaneous clonus, OR
- Inducible clonus with agitation or diaphoresis, OR
- Ocular clonus with agitation or diaphoresis, OR
- Tremor and hyperreflexia, OR
- Hypertonia with temperature >38°C (100.4°F) AND ocular or inducible clonus
Timing and Onset
- Symptoms develop rapidly within minutes to hours, with most cases manifesting within 6-24 hours after medication initiation, dose increase, or addition of a second serotonergic agent 1, 8
- The condition is non-idiosyncratic, meaning it can predictably occur with drug interactions or dose changes 1, 8
Severe Manifestations and Complications
In severe cases (approximately 25% require ICU admission), watch for: 8
- Severe hyperthermia >41.1°C 1
- Rhabdomyolysis with elevated creatine kinase 1
- Metabolic acidosis 1
- Renal failure with elevated serum creatinine 1
- Seizures 1
- Disseminated intravascular coagulopathy 1
- Multiple organ failure 1
Critical Pitfalls
The mortality rate is approximately 11%, making early recognition essential 1, 8. The presentation is extremely variable, and mild cases may be easily missed 2. There are no pathognomonic laboratory findings—diagnosis is purely clinical based on history and physical examination 1. The condition can be confused with neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic syndrome, or withdrawal syndromes, but the presence of hyperreflexia and clonus strongly favors serotonin syndrome 8, 4.