Signs and Symptoms of Serotonin Syndrome
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, increasing, or combining serotonergic medications. 1, 2
Mental Status Changes
- Agitated delirium is the most common mental status alteration 1
- Confusion ranging from mild disorientation to severe altered consciousness 1
- In severe cases, altered consciousness can progress to coma 1
Neuromuscular Abnormalities (Most Diagnostic Features)
Clonus and hyperreflexia are the most diagnostic features when occurring with serotonergic drug use and should be actively sought during examination. 1, 2
- Spontaneous clonus (involuntary rhythmic muscle contractions) 1, 2
- Inducible clonus (triggered by rapid passive stretch of muscles) 1, 2
- Ocular clonus (horizontal eye movement abnormalities) 1, 2
- Hyperreflexia (exaggerated deep tendon reflexes, often more pronounced in lower extremities) 1, 2
- Myoclonus (present in 57% of cases) 1, 3
- Tremor (particularly when combined with hyperreflexia) 1, 4
- Muscle rigidity (can progress to severe hypertonia in severe cases) 1
Autonomic Hyperactivity
- Hyperthermia - temperature elevation up to 41.1°C (106°F) in severe cases 1
- Tachycardia (rapid heart rate, often >100 bpm) 1, 5
- Tachypnea (rapid breathing) 1
- Hypertension or blood pressure fluctuations (≥20 mm Hg diastolic or ≥25 mm Hg systolic change within 24 hours) 1
- Diaphoresis (profuse sweating) 1, 5, 4
- Mydriasis (dilated pupils) 1, 6
- Diarrhea 6, 4
Timing and Onset
Symptoms develop rapidly, typically within minutes to hours (usually 6-24 hours) after initiating a serotonergic medication, increasing the dose, or adding a second serotonergic agent. 1, 2, 3 This rapid onset distinguishes serotonin syndrome from other conditions like neuroleptic malignant syndrome, which develops more gradually. 1
Severity Spectrum
The presentation is extremely variable, and mild cases may be easily missed. 1 The condition ranges from:
- Mild cases: Subtle tremor, mild agitation, diaphoresis, hyperreflexia 2, 7
- Moderate cases: More pronounced neuromuscular findings with temperature 38-40°C 2
- Severe cases (medical emergency): Hyperthermia >41.1°C, severe muscle rigidity, multiple organ failure, with an 11% mortality rate 1, 2, 3
Critical Diagnostic Pitfall
There are no pathognomonic laboratory or radiographic findings for serotonin syndrome - diagnosis is entirely clinical based on the presence of characteristic signs and symptoms in the setting of serotonergic drug exposure. 1 The condition is non-idiosyncratic, meaning it is predictable and can occur with any increase in serotonergic activity, not just idiosyncratic reactions. 1, 3
Complications to Monitor For
In severe cases, watch for: