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 after starting or increasing a serotonergic medication. 1
Mental Status Changes
The neuropsychiatric manifestations include:
- Agitated delirium is the most common mental status change 1
- Confusion ranging from mild disorientation to severe altered consciousness 1
- Altered consciousness that can progress from mild confusion to coma in severe cases 1
- Restlessness and agitation are frequently observed 2
Autonomic Hyperactivity
The autonomic nervous system dysfunction manifests as:
- Hyperthermia with temperatures reaching up to 41.1°C (106°F) 1
- Tachycardia (rapid heart rate) 1, 3
- 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, 3
- Mydriasis (dilated pupils) 1, 3
- Diarrhea may also occur 3
Neuromuscular Abnormalities
Clonus and hyperreflexia are considered highly diagnostic for serotonin syndrome when they occur in the setting of serotonergic drug use. 1, 4
The neuromuscular findings include:
- Myoclonus (present in 57% of cases) 5
- Hyperreflexia (exaggerated reflexes) 1, 4
- Clonus (rhythmic muscle contractions), which can be spontaneous, inducible, or ocular 1, 4
- Muscle rigidity 1, 2
- Tremor 1, 3
Timing and Onset
- 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, 5
- The condition is non-idiosyncratic, meaning it can occur with addition of a new drug, increased dosage of an existing drug, or addition of a second serotonergic drug 1, 5
Severity Spectrum
The presentation of serotonin syndrome is extremely variable, and mild cases may be easily missed. 1
Severe Serotonin Syndrome Features:
- Rapid onset of severe hyperthermia (>41.1°C) 1
- Severe muscle rigidity 1
- Multiple organ failure 1
- Complications including rhabdomyolysis with elevated creatine kinase, metabolic acidosis, elevated serum aminotransferase, renal failure, seizures, and disseminated intravascular coagulopathy 1, 4
- Mortality rate is approximately 11% 1, 4
Critical Diagnostic Pitfall
There are no pathognomonic laboratory or radiographic findings for serotonin syndrome - diagnosis is purely clinical based on the presence of the characteristic triad in the context of serotonergic medication use. 1 The condition can be confused with neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic syndrome, and withdrawal syndromes, but the presence of hyperreflexia and clonus (rather than lead pipe rigidity) helps distinguish serotonin syndrome. 1, 4