Serotonin syndrome

Last updated: August 22, 2023

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Summarytoggle arrow icon

Serotonin syndrome is a potentially life-threatening condition caused by serotonergic overactivity due to the use of serotonergic drugs. It can be caused by a therapeutic dose or overdose of a serotonergic drug, concomitant use of multiple serotonergic drugs, or interactions with CYP450 inhibitors. Onset is typically rapid, occurring within 24 hours of drug administration. Classic features include autonomic dysfunction, neuromuscular excitability (e.g., rigidity, hyperreflexia), and altered mental status. Increased neuromuscular activity can also lead to hyperthermia. Serotonin syndrome is a clinical diagnosis but laboratory studies may be used to assess for complications such as rhabdomyolysis. Management involves discontinuation of serotonergic drugs and treatment of features of serotonin syndrome (e.g., agitation, hyperthermia). In most cases, symptoms resolve within 24 hours of cessation of serotonergic drugs. In moderate to severe cases, pharmacological treatment with cyproheptadine may be indicated. Patients with features of severe disease, e.g., life-threatening hyperthermia, may also require sedation and intubation.

Definitiontoggle arrow icon

Serotonin syndrome is a potentially life-threatening condition caused by serotonergic overactivity in patients with exposure to serotonergic drugs.

Etiologytoggle arrow icon

Serotonergic drugs [2]

Risk factors [3]

Concurrent use of multiple serotonergic drugs, or serotonergic drugs plus certain CYP450 inhibitors, increases the risk and severity of serotonin syndrome.

Clinical featurestoggle arrow icon

Symptom progression [2]

  • Onset: acute, typically within 24 hours of administration of the causative drug
  • Resolution: rapid, typically within 24 hours of treatment initiation

Presentation [2]

HAHA! Serotonin syndrome is no joke: Hyperthermia, Autonomic dysfunction, Hyperreflexia, Altered mental status

To differentiate between serotonin syndrome and other drug-induced hyperthermia conditions, remember that only SErotonin Shakes your Extremities (myoclonus and hyperreflexia, mostly of the lower limbs).

Diagnosticstoggle arrow icon

General principles[2][6]

Diagnostic criteria [7]

Presence of any of the following in patients with exposure to ≥ 1 serotonergic drug :

Laboratory studies [2]

Differential diagnosestoggle arrow icon

Managementtoggle arrow icon

All patients [2][9]

The goal of management is the stabilization of vital signs.

Symptom-specific management [2][9][11]

Avoid physical restraints, as they can lead to worsening hyperthermia and lactic acidosis.

Moderate to severe and/or refractory cases [2][6][10][11]

Rule out anticholinergic syndrome prior to administration of cyproheptadine, as cyproheptadine can worsen anticholinergic syndrome. [9]

Avoid bromocriptine and dantrolene, as bromocriptine may worsen symptoms of serotonin syndrome and dantrolene has not been shown to be effective. [2][11]

Agents other than cyproheptadine, e.g., chlorpromazine, are not currently recommended for the treatment of serotonin syndrome. [2][6][10]

Disposition [2][9][11]

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Preventiontoggle arrow icon

Refer to drug monographs or consult a local pharmacist for more information on drug interactions, half-lives, and washout periods. [8]

Referencestoggle arrow icon

  1. Foong AL, Grindrod KA, Patel T, Kellar J. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician. 2018; 64 (10): p.720-727.
  2. American Psychiatric Association Practice Guidelines for the Treatment of Patients With Major Depressive Disorder. Updated: October 1, 2010. Accessed: October 25, 2020.
  3. $Contributor Disclosures - Serotonin syndrome. All of the relevant financial relationships listed for the following individuals have been mitigated: Alexandra Willis (copyeditor, was previously employed by OPEN Health Communications). None of the other individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy:.
  4. Boyer EW, Shannon M. The Serotonin Syndrome. N Engl J Med. 2005; 352 (11): p.1112-1120.doi: 10.1056/nejmra041867 . | Open in Read by QxMD
  5. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013; 13 (4): p.533-540.
  6. Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014; 348 (feb19 6): p.g1626-g1626.doi: 10.1136/bmj.g1626 . | Open in Read by QxMD
  7. Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010; 81 (9): p.1139-42.
  8. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003; 96 (9): p.635-642.doi: 10.1093/qjmed/hcg109 . | Open in Read by QxMD
  9. Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen's Emergency Medicine 10th edition- Concepts and Clinical Practice E-Book. Elsevier Health Sciences ; 2022
  10. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. Goldfrank's Toxicologic Emergencies, 11th edition. McGraw-Hill Education ; 2019
  11. Wang RZ, Vashistha V, Kaur S, Houchens NW. Serotonin syndrome: Preventing, recognizing, and treating it. Cleve Clin J Med. 2016; 83 (11): p.810-816.doi: 10.3949/ccjm.83a.15129 . | Open in Read by QxMD
  12. Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res. 2019; 12: p.117864691987392.doi: 10.1177/1178646919873925 . | Open in Read by QxMD

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