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