Serotonin syndrome in the intensive care unit: clinical presentations and precipitating medications

Neurocrit Care. 2014 Aug;21(1):108-13. doi: 10.1007/s12028-013-9914-2.


Background: Serotonin syndrome (SS) is becoming a more frequent diagnosis in the intensive care unit (ICU). We sought to determine the clinical presentation, drug exposures, and outcomes of SS in critically ill patients.

Methods: A retrospective study of 33 consecutive ICU patients with SS between March 2007 and March 2012 in ICUs in a large teaching hospital. SS was defined using the Hunter Serotonin Toxicity Criteria.

Results: Seventeen patients (52%) were admitted for mental status changes, including seven patients (21%) with drug overdose and four cases (12%) in which SS was considered the primary admission diagnosis. In 13 patients (39%) the features of SS developed only after a mean of 6.8 ± 9 days of hospitalization. Most received multiple serotonergic drugs upon diagnosis (median three drugs, range 1-5). Antidepressants were the serotonergic medications most often used before admission, and opioids (principally fentanyl) and antiemetics were the most frequently prescribed new serotonin-enhancing medications. Altered mental status was present in all patients and myoclonus, rigidity, and hyperreflexia were the most prevalent examination signs. All but one patient had documented recovery. The mean time to neurological improvement was 56 ± 5 h, but ranged from 8 to 288 h. There were no cases of renal failure related to rhabdomyolysis, or death or persistent disability caused by SS.

Conclusion: SS in the ICU occurs most often because of exposure to multiple serotonergic agents. Continuation of antidepressants plus the addition of opioids and antiemetics during hospitalization are most commonly responsible for this complication.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiemetics / adverse effects
  • Female
  • Humans
  • Intensive Care Units / statistics & numerical data
  • Male
  • Middle Aged
  • Narcotics / adverse effects*
  • Serotonin Agents / adverse effects*
  • Serotonin Syndrome / chemically induced*
  • Serotonin Syndrome / physiopathology*
  • Young Adult


  • Antiemetics
  • Narcotics
  • Serotonin Agents