Epidemiology

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Etiology

Serotonergic drugs

• Antidepressants (e.g., MAOIs, SSRIs, SNRIs, tricyclic antidepressants, vortioxetine, vilazodone, trazodone)
• Anxiolytics (e.g., buspirone)
• Anticonvulsants (e.g., valproate)
• Opioids (e.g., tramadol, meperidine)
• NMDA receptor antagonists (e.g., dextromethorphan)
• 5-HT3 receptor antagonists (e.g., ondansetron)
• Serotonin receptor agonists (e.g., triptans, ritonavir)
• Antibiotics (e.g., linezolid)
• Herbal supplements (e.g., St. John’s wort, ginseng, tryptophan)
  • Tryptophan is precursor of serotonin
• Recreational stimulants (e.g., MDMA, cocaine)

Tip

Serotonin syndrome rarely occurs with a single serotonergic drug used at therapeutic doses. More commonly, it is due to the combined effects of several serotonergic medications, overdose, and/or a drug-drug interaction. E.g. a depressed patient also takes linezolid.

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Pathophysiology

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Clinical features

• Onset: acute, typically within 24 hours of administration of the causative drug
• Classic triad
  • Autonomic dysfunction
    • Diaphoresis
    • Tachycardia
    • Hypertension
    • Mydriasis
  • Neuromuscular excitability: can lead to hyperthermia
    • Contrast to Parkinson disease
    • Hyperreflexia
    • Myoclonus
    • Clonus
    • Horizontal ocular clonus
    • Hypertonicity
    • Rigidity (especially in the lower extremities)
  • Altered mental status
    • Delirium
    • Psychomotor agitation

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Diagnostics

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Treatment

• Agitation and excessive muscle activity: Treat with benzodiazepines.
• Hyperthermia: Initiate cooling measures, e.g., by reducing ambient temperature, applying cooling blankets or ice packs, administering cold IV fluids.
• Autonomic instability
  • Give antihypertensive treatment.
  • Treat MAOI-induced hypotension or shock.
• Moderate to severe and/or refractory cases
  • Consider treatment with 5-HT2A receptor antagonists: cyproheptadine

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