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, 2
Mental Status Changes
- Agitated delirium is the most common mental status manifestation 1
- Confusion and anxiety are frequently observed 1, 3
- Mental state changes range from mild agitation to severe altered consciousness 4
Neuromuscular Abnormalities (Most Diagnostically Specific)
- Clonus and hyperreflexia are the most diagnostically specific findings when occurring with serotonergic drug use 1, 2
- Spontaneous clonus (involuntary rhythmic muscle contractions) is highly specific 1, 5
- Inducible clonus (triggered by rapid dorsiflexion of the ankle) with agitation or diaphoresis 1, 5
- Ocular clonus (horizontal eye movement abnormalities) with agitation or diaphoresis 1, 5
- Myoclonus (brief, shock-like muscle jerks) occurs in 57% of cases 6
- Muscle rigidity, particularly in severe cases 1, 3
- Tremor, especially when combined with hyperreflexia 1, 5
Autonomic Hyperactivity
- Hyperthermia is present in 61% of cases, with temperatures reaching up to 41.1°C (106°F) 1, 7
- Tachycardia (rapid heart rate) 1
- Tachypnea (rapid breathing) 1
- Hypertension 1
- Diaphoresis (profuse sweating) is a common autonomic sign 1, 3
- Mydriasis (dilated pupils) 1
- Flushing 8
- Shivering 3
Gastrointestinal Symptoms
- Diarrhea may occur 3
Severe Manifestations (Medical Emergency)
- Severe hyperthermia >41.1°C with rapid onset 1
- Seizures occur in 36% of fatal cases 7
- Severe muscle rigidity leading to rhabdomyolysis with markedly elevated creatine kinase 1, 7
- Multiple organ failure including renal failure, metabolic acidosis, elevated liver enzymes, and disseminated intravascular coagulopathy 1, 2
Critical Timing and Diagnostic Pitfalls
- Symptoms develop rapidly—within minutes to hours, typically 6-24 hours after medication initiation, dose increase, or adding a second serotonergic agent 1, 2
- Approximately 50% of fatal cases die within 24 hours of symptom onset, emphasizing the need for immediate recognition 7
- The condition can occur with maintenance dosing, first-time drug initiation, or drug combinations 7
- There are no pathognomonic laboratory or radiographic findings—diagnosis is purely clinical 1
- The mortality rate is approximately 11%, with one-quarter of patients requiring intubation and ICU admission 2, 6