Serotonin Toxicity: Implications for Clinical Practice


Serotonin toxicity
serotonin syndrome
selective serotonin reuptake inhibitors
tricyclic antidepressants
monoamine oxidase inhibitors
adverse drug reactions
drug overdoses
diagnostic criteria
clinical practice

How to Cite

Rotheram A, Harris W, Curtain C, Nihill D. Serotonin Toxicity: Implications for Clinical Practice. Australasian Journal of Paramedicine [Internet]. 2016Jul.31 [cited 2023Jun.4];13(3). Available from:


Serotonin toxicity, or serotonin syndrome, is a potentially life threatening adverse reaction to the use of one or more serotonergic drugs. Patients presenting with low level obscure symptoms may have pathophysiology rooted in adverse dopamine and serotonergic poly-pharmacy reactions involving illegal, over-the-counter and/or prescription drugs. In this clinical information paper an overview of serotonin toxicity, diagnostic criteria, and management strategies will be offered. Cultivating a high index of suspicion for serotonin toxicity across a broad patient demographic is recommended


Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med 2009;60:355–66.

Iqbal MM, Basil MJ, Kaplan J, Iqbal MT. Overview of serotonin syndrome. Ann Clin Psychiatry 2012;24:310–8.

Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004;42:277–85.

Deshauer D, Moher D, Fergusson D, Moher E, Sampson M, Grimshaw J. Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ 2008;178:1293–301.

Duncan T, David I, Cecilie L, John M, Simone S, Dana W. Serotonin syndrome. Australian Drug Reactions Advisory Committee, February 2004. Report No.: Contract No.: 1.

McManus P, Mant A, Mitchell PB, Montgomery WS, Marley J, Auland ME. Recent trends in the use of antidepressant drugs in Australia, 1990-1998. Med J Aust 2000;173:458–61.

Stephenson CP, Karanges E, McGregor IS. Trends in the utilisation of psychotropic medications in Australia from 2000 to 2011. Aust N Z J Psychiatry 2013;47:74–87.

Rossi S, editor. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2015.

Michael H. Serotonin syndrome. Australian Prescriber 2003;26:62–3.

Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician 2008;54:988–92.

Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J 2013;13:533–40.

Harvey B. Author request for information fromTGA regarding serotonin toxicity reports. In: Curtain C, editor. TGA; December 23 2015.

Ringland C, Mant A, McGettigan P, et al. Uncovering the potential risk of serotonin toxicity in Australian veterans using pharmaceutical claims data. Br J Clin Pharmacol 2008;66:682–8.

Armenian P, Mamantov TM, et al. Multiple MDMA (ecstasy) overdoses at a rave event: a case series. J Intensive Care Med 2013;28:252–8.

Heal DJ, Smith SL, Gosden J, Nutt DJ. Amphetamine, past and present: a pharmacological and clinical perspective. J Psychopharmacol 2013;27:479–96.

Berman SM, Kuczenski R, McCracken JT, London ED. Potential adverse effects of amphetamine treatment on brain and behavior: a review. Mol Psychiatry 2009;14:123–42.

Jhun P, Bright A, Herbert M. Serotonin syndrome and opioids: What's the deal? Ann Emerg Med 2015;65:434–5.

Schenk M, Wirz S. Serotonin syndrome and pain medication: What is relevant for practice? Schmerz 2015;29:229–51.

Clinical-Pharmacology-Research-Institute. P450 drug interaction table 2015. Available at: [Accessed 23 December 2016].

Silins E, Copeland J, Dillon P. Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk. Aust N Z J Psychiatry 2007;41:649–55.

Aware D. Ecstasy – pill purity report by ChemCentre Mt Lawley, Western Australia: Drug Programs Branch, Prevention and Workforce Development Directorate, Drug and Alcohol Office, Government of Western Australia; 2015. Available at: [Acessed 15 May 2015].

Pilgrim JL, Gerostamoulos D, Woodford N, Drummer OH. Serotonin toxicity involving MDMA (ecstasy) and moclobemide. Forensic Sci Int 2012;215:184–8.

2013-14 Illicit Drug Data Report. In: Commission AC, editor. Canberra.

Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician 2010;81:1139–42.

Sternbach H. The serotonin syndrome. Am J Psychiatry 1991;148:705–13.

Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003;96:635–42.

Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. Med J Aust 2007;187:361–5.

Smith JE. Cooling methods used in the treatment of exertional heat illness. Br J Sports Med 2005;39:503–7; Discussion 507.

Heffner AC, Swords D, Kline JA, Jones AE. The frequency and significance of postintubation hypotension during emergency airway management. J Crit Care 2012;27:417.e419–3.

Heffner AC, Swords DS, Nussbaum ML, Kline JA, Jones AE. Predictors of the complication of postintubation hypotension during emergency airway management. ibid. 2012;27:587–93.

Ferrari R, Ceconi C, Guardigli G. Pathophysiological role of heart rate: From ischaemia to left ventricular dysfunction. Eur Heart J (Suppl) 2008;10:F7–10.