Serotonin syndrome

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  • Can be produced by any serotonergic medication
  • Vast majority of cases occur with therapeutic dosages
  • Most common cause of death is severe hyperthermia

Causative Agents

  • SSRIs
  • MAOIs
  • TCAs
  • Drugs of Abuse: Cocaine, Ecstasy, Marijuana
  • Analgesics: Demerol, fentanyl
  • Antiemetics
  • Triptans
  • Bromocriptine
  • OTC: Cough meds, herbal products, St John’s Wort

Clinical Features

  • Altered mental status: Agitated delirium
  • Autonomic Instability: Hyperthermia, Tachycardia, hypertension, diaphoresis [1]
    • Often labile blood pressure, HR
  • Neuromuscular Abnormalities: Myoclonus, ocular clonus, rigidity, hyperreflexia, tremor
    • More pronounced in the lower extremities
    • Myoclonus: most common finding
      • Important to identify because it does not occur in other conditions that mimic serotonin syndrome

Differential Diagnosis

Altered mental status and fever


Hunter Toxicity Criteria Decision Rules

Serotonergic agent plus 1 of the following:

  • Spontaneous clonus
  • Inducible clonus AND (agitation or diaphoresis)
  • Ocular Clonus AND (agitation or diaphoresis)
  • Tremor AND hyperreflexia
  • Hypertonia AND temp >38 AND (ocular clonus or inducible clonus)

84% Sn, 97% Sp


  1. Discontinue all serotonergic drugs
  2. Benzos
    • Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
  3. Cyproheptadine
    • Give if benzos and supportive care fail to improve agitation and abnormal vitals
    • Serotonin antagonist
    • Give 12mg PO/NG; repeat with 2mg q2hr until clinical response is seen (max 32mg/d)
    • Give 4mg q6hr x48hr if pt is responsive to initial dose
  4. Treat hyperthermia
    • Hyperthermia due to increase in muscular activity, not change in set point
    • Intubate and paralyze
    • Standard cooling measures


See Also


  1. Boyer, E. W. and Shannon, M. (2005) ‘The Serotonin Syndrome’, New England Journal of Medicine, 352(11), pp. 1112–1120. doi: 10.1056/nejmra041867