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
Mental Status Changes
- Agitated delirium is the most common mental status alteration in serotonin syndrome 1
- Confusion, hallucinations, delirium, and in severe cases, coma may occur 1, 3
- These mental status changes typically develop within minutes to hours (usually 6-24 hours) after starting or increasing the dose of a serotonergic medication 1, 2
Autonomic Hyperactivity
- Hyperthermia is a cardinal feature, with temperatures potentially reaching up to 41.1°C (106°F) in severe cases 1
- Tachycardia (racing heartbeat) and tachypnea (rapid breathing) are common 1, 3
- Diaphoresis (profuse sweating) occurs frequently 1, 3
- Hypertension or labile blood pressure may be present 1, 3
- Mydriasis (dilated pupils) and flushing can occur 1
Neuromuscular Abnormalities (Most Diagnostic)
- Clonus is the most specific finding and can be spontaneous, inducible, or ocular 1, 2, 4
- Hyperreflexia (exaggerated reflexes) is highly diagnostic when occurring with serotonergic drug use 1, 2
- Myoclonus (muscle jerking) is present in 57% of cases and helps differentiate serotonin syndrome from other conditions 5
- Tremor and muscle rigidity may develop, particularly in severe cases 1, 3
- Incoordination and muscle twitching (overactive reflexes) can occur 3
Gastrointestinal Symptoms
- Nausea, vomiting, and diarrhea are common accompanying symptoms 3
Diagnostic Criteria to Recognize
The Hunter Criteria are recommended for diagnosis and require the presence of a serotonergic agent plus one of the following: 1, 2, 4
- Spontaneous clonus
- Inducible clonus with agitation or diaphoresis
- Ocular clonus with agitation or diaphoresis
- Tremor and hyperreflexia together
- Hypertonia (muscle rigidity), temperature above 38°C (100.4°F), and ocular or inducible clonus
Severity Classification
- Mild cases present with serotonergic features that may cause concern but are not life-threatening 6
- Moderate cases cause significant distress requiring treatment but are not immediately life-threatening 6
- Severe cases are medical emergencies characterized by rapid onset of severe hyperthermia (>41.1°C), muscle rigidity, and multiple organ failure with an 11% mortality rate 1, 5
Critical Complications to Monitor
- Rhabdomyolysis with elevated creatine kinase 1
- Metabolic acidosis 7, 1
- Renal failure with elevated serum creatinine 1
- Seizures and disseminated intravascular coagulopathy 1
- Elevated serum aminotransferases indicating liver dysfunction 1
Important Clinical Pitfalls
- Physical restraints should be avoided as they exacerbate isometric muscle contractions, worsening hyperthermia and lactic acidosis 5, 2
- The condition is non-idiosyncratic, meaning it can occur with addition of a new serotonergic drug, increased dosage, or addition of a second serotonergic agent 1, 5
- Approximately one-quarter of patients require intubation, mechanical ventilation, and ICU admission 5, 2
- Serotonin syndrome can be confused with neuroleptic malignant syndrome, but the presence of myoclonus and hyperreflexia helps differentiate it 5