Serotonin syndrome

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Background

  • Can be produced by any serotonergic medication
  • Majority of cases occur within therapeutic dosages and often from exposure to several different serotonergic drugs, like while switching between antidepressant classes or drugs
  • Most common cause of death is severe hyperthermia
  • Most common cause is ingestion of foods large in L-Tryptophan, along with MAOI, and second is ingestion of SSRI and MAOI[1]

Causative Agents

Clinical Features

  • Altered mental status: Agitated delirium
  • Autonomic Instability: Hyperthermia, tachycardia, hypertension, diaphoresis [2]
    • 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

Diagnosis

Hunter Toxicity Criteria Decision Rules

Serotonergic agent plus 1 of the following[3]:

  • 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

Serotonin syndrome vs Neuroleptic malignant syndrome

  • History of a new serotonergic drug or a dose increase of a serotonergic drug are helpful
  • Serotonin syndrome is usually much more acute in onset than NMS which may develop over days or weeks
  • Presence of ‘lead pipe’ rigidity is typical of NMS, while serotonin syndrome typically manifests with tremor and hyperreflexia
  • Elevations in CK, LFTs, and WBC, coupled with a low iron level, distinguishes NMS from serotonin syndrome among patients taking both neuroleptic and serotonin agonist medications simultaneously

Management

  • Discontinue all serotonergic drugs
  • Aggressive supportive care
    • If pressors required, direct acting (e.g. norepi, epi) preferred, MAO inhibition causes erratic response to dopamine
  • Benzos
    • Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
  • Cyproheptadine[4]
    • Give if benzos and supportive care fail to improve agitation and abnormal vitals
    • Serotonin antagonist
      • Also has antihistamine and anticholinergic properties that may exacerbate other mixed toxicology picture
    • Give 12mg PO/NG; repeat with 2mg q2hr until clinical response is seen (max 32mg/d)
    • Give 4mg q6hr x48hr if patient is responsive to initial dose
  • Chlorpromazine[5]
    • Phenothiazine with antiserotonergic effects
    • 50mg to 100mg IM
    • Avoid in:
      • Hemodynamically unstable patients as can cause serious hypotension[6]
      • Cases in which NMS may still be on the differential
  • Dexmedetomidine[7][8]
    • Small case series found this helpful in adolescent cases refractory to benzos
  • Dantrolene generally not recommended as it can worsen serotonin toxicity[9]
  • Treat hyperthermia
    • Hyperthermia due to increase in muscular activity, not change in set point
    • Intubate and paralyze if temp > 41.1
    • Standard cooling measures

Disposition

  • Severe cases may require intubation and ventilation in ICU
  • 24hr admission for AMS or abnormal vital signs requiring further supportive care
  • Discharge mild cases with minimal intervention required after 6 hrs of observation

See Also

Video

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References

  1. Stork CM. Serotonin Reuptake Inhibitors and Atypical Antidepressants. In: Flomenbaum N, Goldfrank L, Hoffman R, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies. 8th Ed. New York, NY: McGraw-Hill; 2006: 1070-1082
  2. Boyer, E. W. and Shannon, M. (2005) ‘The Serotonin Syndrome’, New England Journal of Medicine, 352(11), pp. 1112–1120. doi: 10.1056/nejmra041867
  3. 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
  4. 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
  5. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100-109
  6. Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008 Jul; 54(7): 988–992.
  7. Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacother. 2014; 48(12):1651-1654.
  8. Duggal HS, Fetchko J. Serotonin syndrome and atypical antipsychotics. Am J Psychiatry. 2002;159(4):672–3.
  9. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17; 352(11):1112-20.