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Diseases

Serotonin syndrome

OVERVIEW

  • Highlights & Basics
  • Images

DIAGNOSIS

  • Diagnostic Approach
  • Risk Factors
  • History & Exam
  • Tests
  • Differential Diagnosis
  • Criteria
  • Screening

TREATMENT

  • Tx Approach
  • Tx Options
  • Emerging Tx
  • Prevention

FOLLOW-UP

  • Overview
  • Complications

REFERENCES

  • Citations
  • Guidelines
  • Credits

PATIENT RESOURCES

  • Patient Instructions

Highlights & Basics

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Key Highlights
  • Serotonin syndrome is the clinical manifestation of excess serotonin in the central nervous system, resulting from the therapeutic use or overdose of serotonergic drugs.

  • Characterized by a triad of clinical features: neuromuscular excitation, autonomic effects, and altered mental status.

  • Better described as a spectrum of toxicity, ranging from mild to severe, rather than a "syndrome".

  • Diagnosis is clinical and should be based on the Hunter Serotonin Toxicity Criteria (HSTC), of which clonus is a key diagnostic feature.

  • Treatment is guided by the severity of toxicity and involves cessation of the drug(s), supportive care, and antiserotonergic drugs in select patients.

Quick Reference

  • History & Exam

    • Key Factors

      • Other Factors

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      • Diagnostics Tests

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        • Treatment Options

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          Definition

          Epidemiology

          Etiology

          Pathophysiology

          content by BMJ Group
          Last updated

          Images

          • Hunter Serotonin Toxicity Criteria (HSTC) algorithm

            Hunter Serotonin Toxicity Criteria (HSTC) algorithm

          Citations

            Key Articles

            • Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626[Abstract]

            • Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205-214.[Abstract]

            • Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96:635-642.[Abstract][Full Text]

            • Chiew AL, Buckley NA. The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes. Clin Toxicol (Phila). 2022 Feb;60(2):143-58.[Abstract]

            Other Online Resources

            • TOXBASE® The primary clinical toxicology database of the National Poisons Information Service.
            • American Association of Poison Control Centers

            Referenced Articles

            • 1. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-1120.[Abstract]

            • 2. Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626[Abstract]

            • 3. Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205-214.[Abstract]

            • 4. Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96:635-642.[Abstract][Full Text]

            • 5. Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43:180-187.[Abstract][Full Text]

            • 6. Stanford SC, Stanford BJ, Gillman PK. Risk of severe serotonin toxicity following co-administration of methylene blue and serotonin reuptake inhibitors: an update on a case report of post-operative delirium. J Psychopharmacol. 2010;24:1433-1438.[Abstract]

            • 7. Gelener P, Gorgulu U, Kutlu G, et al. Serotonin syndrome due to duloxetine. Clin Neuropharmacol. 2011;34:127-128.[Abstract]

            • 8. Isbister GK, Hackett LP, Dawson AH, et al. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Br J Clin Pharm. 2003;56:441-450.[Abstract][Full Text]

            • 9. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705-713.[Abstract]

            • 10. Gummin DD, Mowry JB, Beuhler MC, et al. 2020 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 38th annual report. Clin Toxicol (Phila). 2021 Dec;59(12):1282-501.[Abstract]

            • 11. Isbister GK, Bowe SJ, Dawson A, et al. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol. 2004;42:277-285.[Abstract]

            • 12. Kirschner R, Donovan JW. Serotonin syndrome precipitated by fentanyl during procedural sedation. J Emerg Med. 2010;38:477-480.[Abstract]

            • 13. Monte AA, Chuang R, Bodmer M. Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review. Br J Clin Pharmacol. 2010;70:794-798.[Abstract]

            • 14. Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Physician. 2015 Jul-Aug;18(4):395-400.[Abstract][Full Text]

            • 15. Isbister GK, Downes F, Whyte IM. Olanzapine and serotonin toxicity. Psychiatry Clin Neurosci. 2003;57:241-242.[Abstract]

            • 16. Sclar DA, Robison LM, Castillo LV, et al. Concomitant use of triptan, and SSRI or SNRI after the US Food and Drug Administration alert on serotonin syndrome. Headache. 2012;52:198-203.[Abstract]

            • 17. Evans RW, Tepper SJ, Shapiro RE, et al. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50:1089-1099.[Abstract][Full Text]

            • 18. Isbister GK, Dawson AH, Whyte IM. Comment: serotonin syndrome induced by fluvoxamine and mirtazapine. Ann Pharmacother. 2001;35:1674-1675.[Abstract]

            • 19. Nisijima K, Yoshino T, Yui K, et al. Potent serotonin (5-HT2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res. 2001;890:23-31.[Abstract]

            • 20. Wang RZ, Vashistha V, Kaur S, et al. Serotonin syndrome: Preventing, recognizing, and treating it. Cleve Clin J Med. 2016 Nov;83(11):810-7.[Abstract][Full Text]

            • 21. Chiew AL, Buckley NA. The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes. Clin Toxicol (Phila). 2022 Feb;60(2):143-58.[Abstract]

            • 22. Isbister GK. Comment: serotonin syndrome, mydriasis, and cyproheptadine. Ann Pharmacother. 2001;35:1672-1673.[Abstract]

            • 23. Hegerl U, Bottlender R, Gallinat J, et al. The serotonin syndrome scale: first results on validity. Eur Arch Psychiatry Clin Neurosci. 1998;248:96-103.[Abstract]

            • 24. Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses. Lancet. 1993;342:1419.[Abstract]

            • 25. Graham PM. Successful treatment of the toxic serotonin syndrome with chlorpromazine. Med J Aust. 1997;166:166-167.[Abstract]

            • 26. Power BM, Pinder M, Hackett LP, et al. Fatal serotonin syndrome following a combined overdose of moclobemide, clomipramine and fluoxetine. Anaesth Intensive Care. 1995;23:499-502.[Abstract]

            • 27. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13:100-109.[Abstract]

            • 28. Boddy R, Dowsett RP, Jeganathan D. Sublingual olanzapine for the treatment of serotonin syndrome (abstract). Clin Toxicol. 2006;44:426.

            • 29. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998;16:615-619.[Abstract]

            • 30. Chan BS, Graudins A, Whyte IM, et al. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998;169:523-525.[Abstract]

            • 31. Moss MJ, Hendrickson RG, Toxicology Investigators Consortium (ToxIC). Serotonin toxicity: associated agents and clinical characteristics. J Clin Psychopharmacol. 2019 Nov/Dec;39(6):628-33.[Abstract]

            • 32. Foong AL, Grindrod KA, Patel T, et al. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician. 2018 Oct;64(10):720-727.[Abstract][Full Text]

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