Overview of serotonin syndrome

Ann Clin Psychiatry. 2012 Nov;24(4):310-8.


Background: Serotonin syndrome (SS) is a rare and potentially life-threatening toxic state caused by an adverse drug reaction that leads to excessive central and peripheral serotonergic activity. This excessive serotonin hyperstimulation may be secondary to 1 standard therapeutic dose of a single agent, inadvertent interactions between various drugs, intentionally or unintentionally excessive use of particular drugs, deliberate self-harm, or recreational use of certain drugs. This review article serves as an overview of the epidemiology, pathophysiology, clinical features, diagnosis, differential diagnosis, management, and prevention of SS.

Methods: The authors conducted a MEDLINE search for the period covering 1955 to 2011.

Results: SS commonly occurs after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors. SS classically consists of a triad of signs and symptoms broadly characterized as alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity. However, all 3 triads of SS may not occur simultaneously. Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis. SS can range in severity from mild to life-threatening. Most cases of SS are mild and resolve with prompt recognition and supportive care. Management of SS involves withdrawal of the offending agent(s), aggressive supportive care to treat hyperthermia and autonomic dysfunction, and occasionally the administration of serotonin antagonists--cyproheptadine or chlorpromazine. Patients with moderate and severe cases of SS require inpatient hospitalization.

Conclusions: Psychiatrists, clinicians, and general practitioners must develop increased awareness of SS due to the current increase in the use of serotonergic agents in clinical practice. As SS is a manifestation of adverse pharmacology, it is not considered an idiosyncratic drug reaction, making it predictable and highly preventable. Most cases of SS are mild and easily managed. With prompt recognition and supportive care, more severe cases of SS have a favorable prognosis.

Publication types

  • Review

MeSH terms

  • Drug Combinations
  • Drug Interactions
  • Humans
  • Monoamine Oxidase Inhibitors / adverse effects*
  • Serotonin Agents / adverse effects*
  • Serotonin Syndrome* / chemically induced
  • Serotonin Syndrome* / diagnosis
  • Serotonin Syndrome* / epidemiology
  • Serotonin Syndrome* / physiopathology
  • Serotonin Syndrome* / therapy


  • Drug Combinations
  • Monoamine Oxidase Inhibitors
  • Serotonin Agents