Symptoms of Serotonin Syndrome
Serotonin syndrome is characterized by a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities that occur due to excessive serotonergic activity in the central nervous system. 1, 2
Clinical Presentation
Mental Status Changes
Autonomic Hyperactivity
- Elevated temperature (up to 41.1°C) 1
- Tachycardia 1
- Tachypnea 1
- Hypertension (which may deteriorate to hypotension) 1
- Diaphoresis (excessive sweating) 1, 2
- Flushing 3
- Mydriasis (dilated pupils) 1
- Sialorrhea (excessive salivation) 1
Neuromuscular Abnormalities
- Myoclonus (most common finding, occurring in 57% of cases) 1
- Hyperreflexia 1, 3
- Clonus (spontaneous, inducible, or ocular) 1, 4
- Muscle rigidity (particularly in lower extremities more than upper extremities) 1, 2
- Tremor 1, 3
- Hyperactive bowel sounds and diarrhea 1, 2
Diagnostic Criteria
The Hunter Criteria are most commonly used for diagnosis, which require the presence of one of the following after taking a serotonergic agent 1, 4:
- Spontaneous clonus 4
- Inducible clonus with agitation or diaphoresis 4
- Ocular clonus with agitation or diaphoresis 4
- Tremor and hyperreflexia 4
- Hypertonia, temperature above 38°C, and ocular or inducible clonus 4
According to modified Dunkley criteria, diagnosis can be made if the patient has taken a serotonergic drug within the last 5 weeks and has any of the following 1:
- Tremor and hyperreflexia 1
- Spontaneous clonus 1
- Muscle rigidity, temperature >38°C, and either ocular clonus or inducible clonus 1
- Ocular clonus and either agitation or diaphoresis 1
- Inducible clonus and either agitation or diaphoresis 1
Severity Classification
Serotonin syndrome can range in severity 5, 3:
- Mild: Serotonergic features that may or may not concern the patient 3
- Moderate: Toxicity causing significant distress requiring treatment but not life-threatening 3
- Severe: Medical emergency characterized by rapid onset of severe hyperthermia (>41.1°C), muscle rigidity, and multiple organ failure 1, 3
Complications of Severe Serotonin Syndrome
- Rhabdomyolysis with elevated creatine kinase 1
- Metabolic acidosis 1
- Elevated serum aminotransferase 1
- Renal failure with elevated serum creatinine 1
- Seizures 1
- Disseminated intravascular coagulopathy 1
- Death (mortality rate approximately 11%) 1
Onset and Timing
- Symptoms typically develop within minutes to hours (usually 6-24 hours) after starting or increasing the dose of a serotonergic medication or adding a second serotonergic agent 1
- The condition is non-idiosyncratic, meaning it can occur with the addition of a new drug, increased dosage of an existing drug, or addition of a second serotonergic drug 1
Important Diagnostic Considerations
- Clonus and hyperreflexia are considered highly diagnostic for serotonin syndrome when they occur in the setting of serotonergic drug use 1
- There are no pathognomonic laboratory or radiographic findings for serotonin syndrome 1
- Diagnosis is primarily clinical and based on history of serotonergic medication use combined with characteristic symptoms 4
- The condition is often misdiagnosed due to its diverse and nonspecific clinical manifestations 5
Prompt recognition of these symptoms is critical as serotonin syndrome can be life-threatening if not treated appropriately, but has a favorable prognosis with early intervention 4.