Serotonin toxicity: a practical approach to diagnosis and treatment

Geoffrey K Isbister, Nicholas A Buckley and Ian M Whyte
Med J Aust 2007; 187 (6): 361-365.


  • Geoffrey K Isbister1,2,3
  • Nicholas A Buckley4
  • Ian M Whyte2,3

  • 1 Tropical Toxinology Unit, Menzies School of Health Research, Charles Darwin University, Darwin, NT.
  • 2 Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle Hospital, and University of Newcastle, Newcastle, NSW.
  • 3 Discipline of Clinical Pharmacology and Toxicology, University of Newcastle, Newcastle, NSW.
  • 4 Department of Clinical Pharmacology and Toxicology, Canberra Hospital, and Australian National University, Canberra, ACT.


Competing interests:

None identified.

  • 1. Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol 2005; 28: 205-214.
  • 2. 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.
  • 3. Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004; 42: 277-285.
  • 4. McManus P, Mant A, Mitchell PB, et al. Recent trends in the use of antidepressant drugs in Australia, 1990–1998. Med J Aust 2000; 173: 458-461. <MJA full text>
  • 5. Nisijima K, Yoshino T, Yui K, Katoh S. Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res 2001; 890: 23-31.
  • 6. Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705-713.
  • 7. Haslett CD, Kumar S. Can olanzapine be implicated in causing serotonin syndrome? Psychiatry Clin Neurosci 2002; 56: 533-535.
  • 8. Whyte IM. Serotonin toxicity/syndrome. In: Medical toxicology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2004: 103-106.
  • 9. Shelton RC. The nature of the discontinuation syndrome associated with antidepressant drugs. J Clin Psychiatry 2006; 67 Suppl 4: 3-7.
  • 10. Primavera A, Giberti L, Scotto P, Cocito L. Nonconvulsive status epilepticus as a cause of confusion in later life: a report of 5 cases. Neuropsychobiology 1994; 30: 148-152.
  • 11. Walker MC. Diagnosis and treatment of nonconvulsive status epilepticus. CNS Drugs 2001; 15: 931-939.
  • 12. van Sweden B, Mellerio F. Toxic ictal delirium. Biol Psychiatry 1989; 25: 449-458.
  • 13. Mohammed I, Hussain A. Intrathecal baclofen withdrawal syndrome — a life-threatening complication of baclofen pump: a case report. BMC Clin Pharmacol 2004; 4: 6.
  • 14. Meythaler JM, Roper JF, Brunner RC. Cyproheptadine for intrathecal baclofen withdrawal. Arch Phys Med Rehabil 2003; 84: 638-642.
  • 15. Isbister GK, Hackett LP, Dawson AH, et al. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Br J Clin Pharmacol 2003; 56: 441-450.
  • 16. Radomski JW, Dursun SM, Reveley MA, Kutcher SP. An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria. Med Hypotheses 1999; 55: 218-224.
  • 17. 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.
  • 18. Malberg JE, Sabol KE, Seiden LS. Co-administration of MDMA with drugs that protect against MDMA neurotoxicity produces different effects on body temperature in the rat. J Pharmacol Exp Ther 1996; 278: 258-267.
  • 19. Sanchez V, Camarero J, Esteban B, et al. The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (“ecstasy”)-induced degeneration of 5-HT nerve endings in rat brain. Br J Pharmacol 2001; 134: 46-57.
  • 20. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 1998; 16: 615-619.
  • 21. Boddy R, Ali R, Dowsett R. Use of sublingual olanzapine in serotonin syndrome [abstract]. J Toxicol Clin Toxicol 2004; 42: 725.
  • 22. Boddy R, Dowsett RP, Jeganathan D. Sublingual olanzapine for the treatment of serotonin syndrome [abstract]. Clin Toxicol 2006; 44: 426.
  • 23. Chan BS, Graudins A, Whyte IM, et al. Serotonin syndrome resulting from drug interactions. Med J Aust 1998; 169: 523-525.
  • 24. Graham PM. Successful treatment of the toxic serotonin syndrome with chlorpromazine [letter]. Med J Aust 1997; 166: 166-167.
  • 25. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999; 13: 100-109.
  • 26. Isbister GK, Friberg LE, Duffull SB. Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose. Intensive Care Med 2006; 32: 1060-1065.
  • 27. Murphy GM, Kremer C, Rodrigues HE, Schatzberg AF. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 2003; 160: 1830-1835.


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