Serotonin syndrome

Last updated: March 3, 2023

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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 initiation of supportive measures, e.g., heat dissipation and IV fluid therapy. 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.

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

Serotonergic drugs [1]

Risk factors [2]

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

Symptom progression [1]

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

Presentation [1]

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).

General principles[1][5]

Diagnostic criteria [6]

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

Laboratory studies [1]

General principles [1]

All patients [1][8]

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

Moderate to severe serotonin syndrome [1][8]

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

Refer to drug monographs or consult a local pharmacist for more information on drug interactions, half-lives, and washout periods. [7]

  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. 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
  4. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013; 13 (4): p.533-540.
  5. 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
  6. Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010; 81 (9): p.1139-42.
  7. 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
  8. 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

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