What are the signs of serotonin syndrome?

Signs of Serotonin Syndrome

Serotonin syndrome is diagnosed using the Hunter criteria, which require a patient to have taken a serotonergic drug within the past 5 weeks and exhibit specific symptoms including spontaneous clonus, inducible clonus, ocular clonus, tremor, hyperreflexia, hypertonia, and temperature >38°C. 1

Key Clinical Features

The Hunter Serotonin Toxicity Criteria are the diagnostic standard and require the presence of one of the following features or combinations:

• Neuromuscular Excitation:

  • Spontaneous clonus
  • Inducible clonus with agitation or diaphoresis
  • Ocular clonus with agitation or diaphoresis
  • Tremor and hyperreflexia
  • Hypertonia with temperature >38°C and ocular or inducible clonus 1, 2

• Autonomic Dysfunction:

  • Hyperthermia (>38°C)
  • Tachycardia
  • Diaphoresis (excessive sweating)
  • Hypertension
  • Dilated pupils 3

• Mental Status Changes:

  • Agitation
  • Confusion
  • Anxiety
  • Altered consciousness 3, 4

Severity Classification

Serotonin syndrome presents as a spectrum of toxicity that can be categorized as:

1. Mild: Serotonergic features that may not concern the patient

   • Mild tremor
   • Slight hyperreflexia
   • Mild anxiety

2. Moderate: Toxicity causing significant distress requiring treatment but not life-threatening

   • More pronounced tremor
   • Noticeable hyperreflexia
   • Increased agitation
   • Mild hyperthermia

3. Severe: Medical emergency characterized by:

   • Rapid onset of severe hyperthermia (>41°C)
   • Muscle rigidity
   • Multiple organ failure
   • Approximately 25% of severe cases require intubation and mechanical ventilation 1, 5

Common Pitfalls in Diagnosis

• Misdiagnosis: Serotonin syndrome is often confused with neuroleptic malignant syndrome, malignant hyperthermia, or anticholinergic toxicity 4

• Overlooking medication history: Always check for recent use of serotonergic medications, including:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Monoamine oxidase inhibitors (MAOIs)
  • Tricyclic antidepressants
  • Opioids (particularly tramadol, meperidine)
  • Recreational drugs (MDMA/ecstasy)
  • Herbal supplements (St. John's Wort) 3

• Failure to recognize drug interactions: The most severe cases typically occur with combinations of drugs acting at different sites, especially MAOIs with serotonin reuptake inhibitors 1, 5

Risk Factors

• Taking multiple serotonergic medications simultaneously
• Recent medication changes or dose increases
• The American Academy of Child and Adolescent Psychiatry recommends avoiding combining MAOIs with any other serotonergic medications 1
• Starting second serotonergic medications at higher than recommended doses 1

Clinical Pearls

• Clonus (spontaneous, inducible, or ocular) is the most specific physical finding for serotonin syndrome 2, 5
• Symptoms typically develop rapidly, often within hours of medication changes 4
• Without proper treatment, serotonin syndrome can lead to rhabdomyolysis, renal failure, disseminated intravascular coagulation, seizures, and death, with an approximately 11% mortality rate 1
• The first 24-48 hours after medication changes are the highest risk period for developing symptoms 1

Remember that early recognition of serotonin syndrome is crucial for preventing progression to severe toxicity and potentially fatal outcomes.