High risk and low prevalence diseases: Serotonin syndrome

Am J Emerg Med. 2022 Nov:61:90-97. doi: 10.1016/j.ajem.2022.08.030. Epub 2022 Aug 20.


Introduction: Serotonin syndrome is a rare, frequently misdiagnosed, serious condition with high morbidity.

Objective: This review highlights the pearls and pitfalls of serotonin syndrome, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence.

Discussion: Serotonin syndrome is a potentially deadly toxidrome marked by excess serotonin receptor activity or neurotransmission. Features of serotonin syndrome include 1) neuromuscular excitation such as tremor, hyperreflexia, and clonus; 2) autonomic dysfunction such as tachycardia, hypertension/hypotension, and hyperthermia; and 3) altered mental status such as agitation, delirium, and coma. Although serotonin syndrome may be more obvious in patients who have overdosed on serotonergic agents such as serotonin reuptake inhibitors (SSRIs), multiple other medications may also cause serotonin syndrome. Alternative diagnoses such as sepsis, neuroleptic malignant syndrome, and decompensated hyperthyroidism should be considered. The primary components of therapy include stopping the offending agent and supportive care, which focuses on agitation control, monitoring for and treating hyperthermia, and managing autonomic instability.

Conclusions: An understanding of serotonin syndrome can assist emergency clinicians in diagnosing and managing this disease.

Keywords: Cyproheptadine; Hyperthermia; Serotonin syndrome; Toxicology.

Publication types

  • Review

MeSH terms

  • Humans
  • Neuroleptic Malignant Syndrome*
  • Prevalence
  • Receptors, Serotonin
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin Syndrome* / diagnosis
  • Serotonin Syndrome* / epidemiology
  • Serotonin Syndrome* / therapy


  • Serotonin Uptake Inhibitors
  • Receptors, Serotonin