What is the management of serotonin syndrome?

Management of Serotonin Syndrome

The management of serotonin syndrome requires immediate discontinuation of all serotonergic agents and implementation of supportive care, with benzodiazepines as first-line treatment for agitation and cyproheptadine for moderate to severe cases. 1

Diagnosis

Before initiating treatment, confirm diagnosis using the Hunter criteria, which require:

• Patient has taken a serotonergic drug within past 5 weeks
• One or more of the following symptoms:
  • Spontaneous clonus
  • Inducible clonus with agitation or diaphoresis
  • Ocular clonus with agitation or diaphoresis
  • Tremor and hyperreflexia
  • Hypertonia, temperature >38°C, and ocular or inducible clonus 1

Treatment Algorithm

Step 1: Discontinue Serotonergic Agents

• Immediately stop all medications with serotonergic properties 1, 2
• Common culprits include SSRIs, SNRIs, MAOIs, tricyclic antidepressants, opioids, and recreational drugs like MDMA 3

Step 2: Supportive Care (All Cases)

• Administer IV fluids for hydration 1, 4
• Monitor vital signs, cardiac rhythm, and oxygen saturation continuously 1
• Control agitation with benzodiazepines (first-line) 1, 4

Step 3: Severity-Based Management

Mild Cases:

• Supportive care and benzodiazepines are usually sufficient 2, 4
• Observe for at least 24 hours after symptom resolution 1

Moderate to Severe Cases:

1. Administer cyproheptadine (serotonin antagonist) 1, 4

   • Adult dosing: Initial 12 mg PO, followed by 2 mg every 2 hours if symptoms continue
   • Maintenance: 8 mg every 6 hours
   • Maximum daily dose: 32 mg 5
   • Pediatric dosing (2-6 years): 0.25 mg/kg/day divided into 2-3 doses, not exceeding 12 mg/day
   • Pediatric dosing (7-14 years): 4 mg 2-3 times daily, not exceeding 16 mg/day 5

2. For severe hyperthermia (>41°C):

   • Consider neuromuscular paralysis with non-depolarizing agents 1
   • Intubation and mechanical ventilation (required in approximately 25% of severe cases) 1
   • Active cooling measures 6

Monitoring and Complications

• Monitor for development of:

  • Rhabdomyolysis
  • Renal failure
  • Disseminated intravascular coagulation
  • Seizures 1

• Without proper treatment, mortality can reach approximately 11%, primarily due to respiratory failure 1, 2

Important Considerations

• Serotonin syndrome is often misdiagnosed due to nonspecific symptoms 2, 6
• Differentiate from neuroleptic malignant syndrome, malignant hyperthermia, and anticholinergic toxicity 6
• Patients with Parkinson's disease may be at risk due to medication interactions (e.g., MAOIs like rasagiline) 7
• Most mild to moderate cases resolve within 24-72 hours with proper management 4
• All moderate to severe cases require inpatient hospitalization 4

Prevention

• Avoid combining MAOIs with any other serotonergic medications 1
• Exercise caution when combining two or more non-MAOI serotonergic drugs 1
• Start second serotonergic medications at low doses and increase slowly 1
• Monitor closely for symptoms in the first 24-48 hours after medication changes 1, 3