The serotonin syndrome

Am J Psychiatry. 1991 Jun;148(6):705-13. doi: 10.1176/ajp.148.6.705.


Objective and method: A review of the literature on the serotonin syndrome in animals and human beings was conducted, and 12 reports of 38 cases in human patients were then analyzed to determine the most frequently reported clinical features and drug interactions, as well as the incidence, treatment, and outcome of this syndrome.

Findings: The serotonin syndrome is most commonly the result of the interaction between serotonergic agents and monoamine oxidase inhibitors. The most frequent clinical features are changes in mental status, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. The presumed pathophysiological mechanism involves brainstem and spinal cord activation of the 1A form of serotonin (5-hydroxytryptamine, or 5-HT) receptor. The incidence of the syndrome is not known. Both sexes have been affected, and patients' ages have ranged from 20 to 68 years. Discontinuation of the suspected serotonergic agent and institution of supportive measures are the primary treatment, although 5-HT receptor antagonists may also play a role. Once treatment is instituted, the syndrome typically resolves within 24 hours, but confusion can last for days, and death has been reported.

Conclusions: The serotonin syndrome is a toxic condition requiring heightened clinical awareness for prevention, recognition, and prompt treatment. Further work is needed to establish the diagnostic criteria, incidence, and predisposing factors, to identify the role of 5-HT antagonists in treatment, and to differentiate the syndrome from neuroleptic malignant syndrome.

Publication types

  • Review

MeSH terms

  • Adult
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Basal Ganglia Diseases / chemically induced
  • Basal Ganglia Diseases / physiopathology*
  • Depressive Disorder / drug therapy
  • Depressive Disorder / physiopathology
  • Drug Interactions
  • Drug Therapy, Combination
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / physiopathology
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Neuroleptic Malignant Syndrome / diagnosis
  • Neuroleptic Malignant Syndrome / physiopathology
  • Receptors, Serotonin / physiology
  • Serotonin / physiology*
  • Tryptophan / adverse effects
  • Tryptophan / therapeutic use


  • Antidepressive Agents
  • Monoamine Oxidase Inhibitors
  • Receptors, Serotonin
  • Fluoxetine
  • Serotonin
  • Tryptophan