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[2]:

  • 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


  • Discontinue all serotonergic drugs
  • Benzos
    • Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
  • Cyproheptadine[3]
    • 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
  • Chlorpromazine[4]
    • Phenothiazine with antiserotonergic effects
    • 50mg to 100mg IM
    • Can consider in severe cases
  • Treat hyperthermia
    • Hyperthermia due to increase in muscular activity, not change in set point
    • Intubate and paralyze if temp > 41.1
    • Standard cooling measures
    • Antipyretics not helpful as hyperthermia secondary to muscle activity, not hypothalamic set point increase


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
  2. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003;96:635-642
  3. Graudins, A., Stearman, A. and Chan, B. (1998) ‘Treatment of the serotonin syndrome with cyproheptadine’, The Journal of Emergency Medicine, 16(4), pp. 615–619. doi: 10.1016/s0736-4679(98)00057-2
  4. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100-109