Skip to main content Accessibility help
×
Home

Serotonin syndrome: a spectrum of toxicity

  • Rabia Ellahi
  • Please note an addendum has been issued for this article.

Summary

Serotonin syndrome (serotonin toxicity or serotonin toxidrome) is a potentially serious and theoretically predictable reaction that appears to be rarely diagnosed in practice in the UK. Some symptoms of serotonin syndrome overlap with features of other presentations in psychiatry and thus may be misattributed to mental illness (‘diagnostic overshadowing’). Further, there may be diagnostic dilemmas in patients on combinations of drugs, those receiving drugs with previously unknown serotonergic properties or where there are drug interactions. Prescriber vigilance and holistic review of the patient, including the pharmacotherapy, may be helpful in avoiding progression of serotonin syndrome to more serious outcomes.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Serotonin syndrome: a spectrum of toxicity
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Serotonin syndrome: a spectrum of toxicity
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Serotonin syndrome: a spectrum of toxicity
      Available formats
      ×

Copyright

Corresponding author

Dr Rabia Ellahi, Ailsa Hospital, Ayr KA6 6AB, UK. Email: rellahi1@nhs.net

Footnotes

Hide All

LEARNING OBJECTIVES

• Raised awareness of serotonin syndrome, its clinical presentation and diagnostic criteria

• Recognise multiple pathways that may contribute to the development of serotonin syndrome, with particular emphasis on the importance of the cytochrome P450 enzyme system

• Increased understanding of the importance of early management in preventing progression to more toxic states

Declaration of Interest

None

Footnotes

References

Hide All
Ahuja, N, Cole, AJ (2009) Hyperthermia syndromes in psychiatry. Advances in Psychiatric Treatment, 15: 181–91.
Boyer, E, Shannon, M (2005) The serotonin syndrome. New England Journal of Medicine, 352: 1112–20.
Buckley, AB, Dawson, AH, Isbister, GK (2014) Serotonin syndrome. BMJ, 348: g1626.
Cauli, O, Morelli, M (2005) Caffeine and the dopaminergic system. Behavioural Pharmacology, 16: 6377.
Chander, WP, Singh, N, Mukhiya, GK (2011) Serotonin syndrome in maintenance haemodialysis patients following sertraline treatment for depression. Journal of the Indian Medical Association, 109: 36–7.
Chang, TW, Castle, DJ (2004) Layer upon layer, thermoregulation in schizophrenia. Schizophrenia Research, 69: 149–57.
Chechani, V (2002) Serotonin syndrome presenting as hypotonic coma and apnoea: potentially fatal complications of selective serotonin reuptake inhibitor therapy. Critical Care Medicine, 30: 473–6.
Cooper, BE, Sejnowski, CA (2013) Serotonin syndrome: recognition and treatment. AACN Advanced Critical Care, 24: 1520.
Copeland, J, Dillon, P, Gascoigne, M (2006) Ecstasy and the concomitant use of pharmaceuticals. Addictive Behaviors, 31: 367–70.
Demyttenaere, K, Haddad, P (2000) Compliance with antidepressant therapy and antidepressant discontinuation symptoms. Acta Psychiatrica Scandinavica Supplementum, 403: 50–6.
Dunkley, EJC, Isbister, GK, Sibbritt, D et al (2003) The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM, 96: 635–42.
Ener, RA, Sharon, B, Meglathery, MD et al (2003) Serotonin syndrome and other serotonergic disorders. Pain Medicine, 4: 6374.
Evans, RW, Tepper, SJ, Shapiro, RE et al (2010) 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, 50: 1089–99.
Ferrari, A (2006) Headache: one of the most common and troublesome adverse reactions to drugs. Current Drug Safety, 1: 3458.
Food and Drug Administration (2006) Public health advisory – combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. FDA (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124349.htm). Page last updated 16 Aug 2013.
Fox, MA, Jensen, CL, Gallagher, PS et al (2007) Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology, 53: 643–56.
Fugate, JE, White, RD, Rabinstein, AA (2014) Serotonin syndrome after therapeutic hypothermia for cardiac arrest: a case series. Resuscitation, 85: 774–7.
Gillman, PK (2005) Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95: 434–41.
Gillman, PK (2010a) Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache, 50: 264–72.
Gillman, PK (2010b) CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. Journal of Psychopharmacology, 25: 429–36.
Haddad, PM, Dursun, SM (2008) Neurological complications of psychiatric drugs: clinical features and management. Human Psychopharmacology: Clinical and Experimental, 23: 1526.
Hegerl, U, Bottlender, R, Gallinat, J et al (1998) The serotonin syndrome scale: first results on validity. European Archives of Psychiatry and Clinical Neuroscience, 248: 96103.
Herraiz, T, Chapparo, C (2006) Human monoamine oxidase inhibition by coffee and beta-carbolines norharman and harman isolated from coffee. Life Sciences, 78: 795802.
Iqbal, MM, Miles, JB, Kaplan, J et al (2012) Overview of serotonin syndrome. Annals of Clinical Psychiatry, 24: 310–18.
Isbister, IK, Buckley, NA, Whyte, IM (2007) Serotonin toxicity: a practical guide to diagnosis and treatment. Medical Journal of Australia, 187: 361–5.
Jacobs, BL (1974) Effect of two dopamine receptor blockers on a serotonin-mediated behavioural syndrome in rats. European Journal of Pharmacology, 27: 363–6.
Jones, SL, Athan, E, O'Brien, D (2004) Serotonin syndrome due to co-administration of linezolid and venlafaxine. Journal of Antimicrobial Chemotherapy, 54: 289–90.
Kiani, J, Imam, SZ (2007) Medicinal importance of grapefruit juice and its interactions with various drugs. Nutrition Journal, 6: 33.
Krishnamoorthy, S, Ma, Z, Zhang, G et al (2010) Involvement of 5-HT2A receptors in the serotonin syndrome caused by excessive 5-HT efflux in the rat brain. Clinical Pharmacology and Toxicology, 107: 830–41.
Lane, RM (1998) SSRI-induced extrapyramidal side effects and akathisia: implications for treatment. Journal of Psychopharmacology, 12: 192214.
Lee, AJ, Chan, WK, Harralson, AF et al (1999) The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clinical Therapeutics, 21: 1890–9.
Lee, YC, Chen, PP (2010) A review of SSRIs and SNRIs in neuropathic pain. Expert Opinion on Pharmacotherapy, 11: 2813–25.
Lingam, R, Scott, J (2002) Treatment non-adherence in affective disorders. Acta Psychiatrica Scandinavica, 105: 164–72.
Lynch, T, Price, A (2007) The effect of cytochrome P450 metabolism on drug response, interactions and adverse effects. American Family Physician, 76: 391–6.
Monte, A, Chuang, R, Bodmer, M (2010) Dextromethorphan, chlorpheniramine and serotonin toxicity: case report and systemic literature review. British Journal of Clinical Pharmacology, 70: 794–8.
Morris, R, Matthes, J (2015) Serotonin syndrome in a breast-fed neonate. BMJ Case Reports, DOI: 10.1136/bcr-2015–209418 (published online 6 May).
Morrish, PK (2014) Serotonin syndrome. BMJ, 348: g1626.
Odagaki, Y (2009) Atypical neuroleptic malignant syndrome or serotonin toxicity associated with atypical antipsychotics? Current Drug Safety, 4: 8493.
Okamoto, N, Sakomoto, K, Yamada, M (2012) Transient serotonin syndrome by concurrent use of electroconvulsive therapy and selective serotonin reuptake inhibitor: a case report and review of the literature. Case Reports in Psychiatry, 2012: article ID 215214.
Park, SH, Wackermah, RC, Stimmel, GL (2014) Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants? Journal of Pharmacy Practice, 27: 71–8.
Prakash, S, Belani, P, Trivedi, A (2014) Headache as a presenting feature in patients with serotonin syndrome: a case series. Cephalalgia, 34: 148–53.
Radomski, JW, Dursun, SM, Reveley, MA et al (1999) An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria. Medical Hypotheses, 55: 218–24.
Shaikh, Z, Krueper, S, Malins, T (2011) Serotonin syndrome: take a close look at the unwell surgical patient. Annals of The Royal College of Surgeons of England, 93: 569–72.
Shee, JC (1960) Dangerous potentiation of pethidine by iproniazid and its treatment. BMJ, 2: 507–9.
Shioda, K, Nisijima, K, Nishida, S et al (2004) Possible serotonin syndrome arising from an interaction between caffeine and serotonergic antidepressants. Human Psychopharmacology: Clinical and Experimental, 19: 353–4.
Silins, E, Copeland, J, Dillon, P (2007) Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk. Australian & New Zealand Journal of Psychiatry, 41: 649–55.
Steele, D, Keltner, NL, McGuiness, TM (2011) Are neuroleptic malignant syndrome and serotonin syndrome the same syndrome? Perspectives in Psychiatric Care, 47: 5862.
Sternbach, H (1991) The serotonin syndrome. American Journal of Psychiatry, 148: 705–13.
Sun-Edelstein, C, Tepper, SJ, Shapiro, RE (2008) Drug-induced serotonin syndrome: a review. Expert Opinion on Drug Safety, 7: 587–96.
Tomaselli, G, Modestin, J (2004) Repetition of serotonin syndrome after re-exposure to SSRI: a case report. Journal of Pharmacopsychiatry, 37: 236–8.
Volpie-Abadie, J, Kaye, A, Kaye, D (2013) Serotonin syndrome. Ochsner Journal, 13: 533–40.
Zhou, S, Chan, E, Pan, SQ (2004) Pharmacokinetic interactions of drugs with St John's Wort. Journal of Psychopharmacology, 18: 262–76.
Zhou, SF (2009) Polymorphisms of human cytochrome P450 2D6 and its clinical significance: Part 1. Clinical Pharmacokinetics, 48: 689723.

Related content

Powered by UNSILO

Serotonin syndrome: a spectrum of toxicity

  • Rabia Ellahi
  • Please note an addendum has been issued for this article.

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.

Serotonin syndrome: a spectrum of toxicity

  • Rabia Ellahi
  • Please note an addendum has been issued for this article.
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *



An addendum has published for this article: