Serotonin Syndrome

A potentially life-threatening condition characterized by excess serotonergic activity in the central and peripheral nervous systems. Most commonly occurs due to drug interactions or overdose of serotonergic medications.

Key Points

• Rapid onset: Usually within 24 hours of medication change/addition
• Mortality rate: 2-12% if untreated
• Most common in ages 15-24 years
• Higher incidence in females

Common Triggering Medications

• SSRIs (Fluoxetine, Sertraline, Paroxetine)
• SNRIs (Venlafaxine, Duloxetine)
• MAOIs (Phenelzine, Tranylcypromine)
• Tricyclic antidepressants
• Over-the-counter medicines containing dextromethorphan
• St. John's Wort
• Lithium
• Tramadol

Clinical Manifestations

The classic triad includes:

• Mental Status Changes:
  • Agitation
  • Anxiety
  • Confusion
  • Hypomania
  • Restlessness
• Autonomic Hyperactivity:
  • Hyperthermia (>38.5°C)
  • Tachycardia
  • Hypertension
  • Diaphoresis
  • Mydriasis
  • Flushing
• Neuromuscular Abnormalities:
  • Hyperreflexia
  • Clonus (spontaneous, inducible, ocular)
  • Muscle rigidity
  • Tremor
  • Myoclonus

Severity Grading

• Mild: Afebrile, mild hypertension, tachycardia
• Moderate: Fever up to 40°C, hyperreflexia, clonus
• Severe: Fever >41.1°C, sustained clonus, rhabdomyolysis

Diagnostic Criteria (Hunter Criteria)

Presence of a serotonergic agent plus ONE of the following:

• Spontaneous clonus
• Inducible clonus + agitation/diaphoresis
• Ocular clonus + agitation/diaphoresis
• Tremor + hyperreflexia
• Hypertonia + temperature >38°C + ocular/inducible clonus

Differential Diagnosis

• Neuroleptic Malignant Syndrome
• Malignant Hyperthermia
• Anticholinergic Toxicity
• Sepsis
• Encephalitis
• Heat Stroke
• Thyroid Storm

Laboratory Studies

• Complete Blood Count
• Comprehensive Metabolic Panel
• Creatine Kinase
• Coagulation Profile
• Urine Drug Screen
• Serum Drug Levels (if applicable)

Treatment Approach

• Immediate Actions:
  • Discontinue all serotonergic agents
  • Supportive care
  • Temperature control
  • IV fluids
• Pharmacological Management:
  • Benzodiazepines for agitation/tremor
  • Cyproheptadine (serotonin antagonist)
    • Initial dose: 12mg orally
    • Maintenance: 2mg every 2 hours
    • Maximum: 32mg/24 hours
• Severe Cases:
  • ICU admission
  • Possible intubation
  • Neuromuscular paralysis
  • Active cooling

Monitoring

• Continuous cardiac monitoring
• Frequent vital signs
• Core temperature
• Mental status
• Neuromuscular examination

Prevention

• Careful medication reconciliation
• Awareness of drug interactions
• Patient education
• Appropriate washout periods when switching medications