Contributor: Jorge Chalit-Hernandez, OMS3

Educational Pearls:

• Serotonin syndrome occurs most commonly due to the combination of monoamine oxidase inhibition with concomitant serotonergic medications like SSRIs

• Examples of unexpected monoamine oxidase inhibitors

  • Linezolid - a last-line antibiotic reserved for patients with true anaphylaxis to penicillins and cephalosporins

  • Methylene blue - not mentioned in the podcast due to its uncommon usage for methemoglobinemia

• Other medications that can interact with SSRIs to cause serotonin syndrome

  • Dextromethorphan - primarily an anti-tussive at sigma opioid receptors that also has serotonin reuptake inhibition

• Clinical presentation of serotonin syndrome

  • Altered mental status

  • Autonomic dysregulation leading to hypertension (most common), hypotension, and tachycardia

  • Hyperthermia

  • Neuromuscular hyperactivity - tremors, myoclonus, and hyperreflexia

• Hunter Criteria (high sensitivity and specificity for serotonin syndrome):

  • Spontaneous clonus

  • Inducible clonus + agitation or diaphoresis

  • Ocular clonus + agitation or diaphoresis

  • Tremor + hyperreflexia

  • Hypertonia, temperature > 38º C, and ocular or inducible clonus

• Management of serotonin syndrome

  • Primarily supportive - benzodiazepines can help treat hypertension, agitation, and hyperthermia. Patients often require repeated and higher dosing of benzodiazepines

  • Avoid antipyretics to treat hyperthermia since the elevated temperature is due to sustained muscle contraction and not central temperature dysregulation

  • In refractory patients, cyproheptadine (a 5HT2 antagonist) may be used as a second-line treatment

  • Patients with temperatures > 41.1º C or 106º F require medically induced paralysis and intubation to control their temperature

References

1. Boyer EW, Shannon M. The serotonin syndrome [published correction appears in N Engl J Med. 2007 Jun 7;356(23):2437] [published correction appears in N Engl J Med. 2009 Oct 22;361(17):1714]. N Engl J Med. 2005;352(11):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(9):635-642. doi:10.1093/qjmed/hcg109

3. Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152(6):946-951. doi:10.1038/sj.bjp.0707430

4. Schwartz AR, Pizon AF, Brooks DE. Dextromethorphan-induced serotonin syndrome. Clin Toxicol (Phila). 2008;46(8):771-773. doi:10.1080/15563650701668625

5. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry. 2004;43(7):790. doi:10.1097/01.chi.0000128830.13997.aa

Summarized & Edited by Jorge Chalit, OMS3

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