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 as the serotonin antagonist of choice for moderate to severe cases. 1

Diagnosis and Assessment

Before initiating treatment, confirm the diagnosis using the Hunter criteria, which have higher sensitivity (84%) and specificity (97%) than other diagnostic criteria 1:

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

Assess severity based on clinical presentation:

• Mild: Tremor, hyperreflexia, mild agitation, diaphoresis
• Moderate: Tachycardia, hypertension, hyperthermia (38-40°C), increased bowel sounds, ocular clonus
• Severe: Temperature >41.1°C, severe hypertension/tachycardia, delirium, muscle rigidity

Treatment Algorithm

Step 1: Discontinue Offending Agent(s)

• Immediately stop all serotonergic medications 1, 2
• Identify and document all potential serotonergic agents including:
  • SSRIs, SNRIs, TCAs, MAOIs
  • Opioids (particularly tramadol, meperidine, fentanyl)
  • Antibiotics with serotonergic properties
  • Over-the-counter medications and supplements (e.g., St. John's Wort) 3

Step 2: Supportive Care

• For all cases:

  • IV fluid administration to address dehydration 1
  • Cardiac monitoring
  • Frequent vital sign checks
  • External cooling measures for hyperthermia 1

• For agitation and neuromuscular symptoms:

  • Benzodiazepines (first-line) 1, 2
    • Diazepam or lorazepam for control of agitation and muscle hyperactivity

Step 3: Pharmacologic Intervention Based on Severity

Mild Cases:

• Supportive care and benzodiazepines usually sufficient
• Monitor for progression to more severe symptoms
• Symptoms typically resolve within 24-72 hours after discontinuation of serotonergic agents 4

Moderate to Severe Cases:

• Cyproheptadine administration 1, 5:
  • Adult dosing: Initial 12 mg orally, followed by 2 mg every 2 hours for continuing symptoms
  • Maintenance dose: 8 mg every 6 hours
  • Maximum daily dose: 32 mg 5
  • Pediatric dosing: 0.25 mg/kg/day divided doses 5
    • Ages 2-6 years: 2 mg (½ tablet) 2-3 times daily (max 12 mg/day)
    • Ages 7-14 years: 4 mg (1 tablet) 2-3 times daily (max 16 mg/day)
  • For patients unable to take oral medications, tablets can be crushed and administered via nasogastric tube 1

Critical Cases (Temperature >41.1°C):

• Immediate interventions:
  • Emergency sedation
  • Neuromuscular paralysis
  • Intubation and mechanical ventilation 1
  • Active cooling measures
  • ICU admission (required in approximately 25% of cases) 1

Special Considerations

Physical Restraints

• Avoid physical restraints as they may worsen hyperthermia and lactic acidosis by exacerbating isometric muscle contractions 1

Laboratory Monitoring

• No pathognomonic laboratory findings exist, but monitor:
  • Complete blood count
  • Electrolytes
  • Renal function (BUN, creatinine)
  • Arterial blood gases (for metabolic acidosis)
  • Liver function tests
  • Creatine kinase (for rhabdomyolysis)
  • Coagulation studies 1

Complications to Monitor

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

Prognosis and Follow-up

With prompt recognition and appropriate management, most cases of serotonin syndrome have a favorable prognosis 4. However, mortality can be approximately 11% in severe cases 1. Symptoms typically resolve within 24 hours of discontinuing the offending agent and initiating treatment, though some cases may take longer.

After resolution, careful consideration should be given before reintroducing any serotonergic medications, with attention to potential drug interactions to prevent recurrence 3.