Serotonin Syndrome

Author: Michelle Lin, MD
Updated: 1/6/2012

Serotonin Syndrome

Classic triad of findings

  • Altered mental status
  • Autonomic instability
  • Neuromuscular hyperactivity

Medications contributing to serotonin syndrome

Amphetamines and derivatives

Analgesics

  • Cyclobenzaprine
  • Fentanyl
  • Meperidine
  • Tramadol

Antidepressants/ mood stabilizers

  • Buspirone
  • Lithium
  • MOA-I
  • SSRIs
  • SNRIs
  • Serotonin 2A-R blockers
  • St. John’s wort
  • Tricyclic antidepressants

Antiemetics

  • Metoclopramide
  • Ondansetron

Antimigraine medications

  • Carbamazepine
  • Ergots
  • Triptans
  • Valproic acid

Miscellaneous

  • Cocaine
  • Dextromethorphan
  • Linezolid
  • L-tryptophan
  • 5-hydroxytryptophan

Tip: Be especially aware of adding drug that inhibits cytochrome P450 2D6 +/- 3A4 (eg. erythromycin) to someone on SSRI.

Hunter's Decision Rule

Sensitivity 84%, Specificity 97%

Hunter's decision Rule diagram

Sternbach's criteria

Need 3 of 10 symptoms: (Sensitivity 75%, specificity 96%)

  • Agitation or restlessness
  • Diaphoresis
  • Diarrhea
  • Hyperreflexia
  • Incoordination or ataxia
  • Confusion
  • Hypomania
  • Myoclonus
  • Shivering
  • Tremor

Differential Diagnosis

  • Anticholinergic syndrome
  • Neuroleptic malignant syndrome
  • Malignant hyperthermia

Sternbach's criteria table

Table adapted from Boyer EW, Shannon M. NEJM 2005

Treatment

Usually supportive (benzodiazepines), although can give cyproheptadine (serotonin 2A antagonist)

References

  • Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20. [PubMed]
  • Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010 May 1;81(9):1139-42. [PubMed]