What is the management of serotonin syndrome?

Management of Serotonin Syndrome

The management of serotonin syndrome primarily involves immediate discontinuation of all serotonergic medications, supportive care, and in moderate to severe cases, administration of cyproheptadine as a specific serotonin antagonist. 1

Diagnosis

Before initiating treatment, confirm the diagnosis using the Hunter criteria, which have superior sensitivity (84%) and specificity (97%) compared to other diagnostic criteria:

• Patient has taken a serotonergic drug within the past 5 weeks
• Plus one of the following:
  • Tremor and hyperreflexia
  • Spontaneous clonus
  • Muscle rigidity, temperature >38°C, and either ocular or inducible clonus
  • Ocular clonus with either agitation or diaphoresis
  • Inducible clonus with either agitation or diaphoresis 2, 1

Treatment Algorithm

Step 1: Discontinue Offending Agent(s)

• Immediately stop all serotonergic medications
• This step alone may be sufficient for mild cases 1, 3

Step 2: Supportive Care (All Cases)

• Intravenous fluids for hydration
• Benzodiazepines for agitation and muscle hyperactivity
  • First-line agent for agitation control 2, 4
• External cooling measures for hyperthermia
• Monitor vital signs continuously, particularly temperature 1
• Avoid physical restraints as they may worsen hyperthermia and lactic acidosis by exacerbating isometric muscle contractions 2, 1

Step 3: Pharmacological Intervention (Moderate to Severe Cases)

• Cyproheptadine (5-HT2A antagonist):
  • Pediatric patients (2-6 years): 0.25 mg/kg/day divided into 2-3 doses, not exceeding 12 mg/day
  • Pediatric patients (7-14 years): 4 mg 2-3 times daily, not exceeding 16 mg/day
  • Adults: Initial dose 12 mg orally, followed by 4-8 mg every 6 hours as needed, maximum 32 mg/day 1, 5
• Do not substitute diphenhydramine for cyproheptadine as it lacks specific serotonin antagonist properties 1

Step 4: Critical Care Management (Severe Cases)

• ICU admission for cases with:
  • Temperature >41.1°C
  • Significant autonomic instability
  • Respiratory compromise
• Consider emergency sedation, neuromuscular paralysis, and intubation
• Approximately 25% of patients require intubation and mechanical ventilation 2, 1

Monitoring

• Vital signs, including continuous temperature monitoring
• Mental status changes
• Neuromuscular abnormalities
• Laboratory studies:
  • Complete blood count
  • Electrolytes
  • Renal function tests
  • Liver function tests
  • Creatine kinase (for rhabdomyolysis)
  • Arterial blood gas (for metabolic acidosis)
  • Coagulation studies 1

Complications to Watch For

• Rhabdomyolysis (elevated creatine kinase)
• Metabolic acidosis
• Elevated liver enzymes
• Renal failure
• Seizures
• Disseminated intravascular coagulation 2, 1

Prognosis

The mortality rate is approximately 11% with significant morbidity associated with serotonin syndrome, highlighting the importance of prompt recognition and treatment 1. With appropriate management, most cases have a favorable prognosis 4, 6.

Prevention

• Avoid combining MAOIs with any other serotonergic medications
• Exercise caution when combining two or more non-MAOI serotonergic drugs
• Close monitoring for symptoms, especially in the first 24-48 hours after dosage changes 1
• Maintain awareness of common culprits: SSRIs, SNRIs, TCAs, MAOIs, opioids, dextromethorphan, and St. John's wort 1, 3