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Serotonin Syndrome

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Movement Disorder Emergencies

Part of the book series: Current Clinical Neurology ((CCNEU))

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Abstract

Serotonin syndrome presents with neuromuscular, autonomic, and mental status changes. Severe cases of serotonin syndrome, also called serotonin toxicity, are characterized by neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity, tremor), autonomic stimulation (hyperthermia, tachycardia, tachypnea, diaphoresis, flushing), and altered mental state (anxiety, agitation, confusion). These more severe cases may come to the clinician’s attention on an emergency basis. The diagnosis of serotonin syndrome should be considered in a patient presenting with any combination of clonus, myoclonus, rigidity, and/or tremor. Serotonin syndrome is associated with the use of one or more serotonergic agents. Severe cases generally occur with combinations of serotonergic drugs, most commonly including a serotonin reuptake inhibitor and a monoamine oxidase inhibitor. Excessive serotonin (5-hydroxytryptamine) in the central nervous system has been implicated. Certain patient populations may be predisposed to developing serotonin toxicity, based on their use of various medications or other substances with serotonergic properties. When evaluating a patient with clinical features of neuromuscular excitation, autonomic stimulation, and/or altered mental state, prompt identification and management are critical, and treatment considerations are often complex.

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References

  1. Oates JA, Sjoerdsma A. Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurology. 1960;10:1076–8.

    Article  PubMed  CAS  Google Scholar 

  2. Mills KC. Serotonin syndrome. Am Fam Physician. 1995;52:1475–82.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  4. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. Hunter serotonin toxicity criteria: a simple and accurate diagnostic decision rule for serotonin toxicity. Q J Med. 2003;96:635–42.

    Article  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  6. Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008;7:587–96.

    Article  PubMed  CAS  Google Scholar 

  7. Gillman PK. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache. 2010;50:264–72.

    Article  PubMed  Google Scholar 

  8. Mohammad-Zadeh LF, Moses L, Gwaltney-Brant SM. Serotonin: a review. J Vet Pharmacol Therap. 2008;31:187–99.

    Article  CAS  Google Scholar 

  9. Van Oekelen D, Megnes A, Meert T, et al. Functional study of rat 5-HT2A receptors using antisense oligonucleotides. J Neurochem. 2003;85:1087–100.

    Article  PubMed  Google Scholar 

  10. Barnes NM, Andrade R, Bockaert J, et al. 5-Hydroxytryptamine receptors, introductory chapter. International Union of Basic and Clinical Pharmacology (IUPHAR) database (IUPHAR-DB). http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=1. Last modified on 2011-04-18; Accessed on 2011-05-04

  11. Gillman PK. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry. 2006;59:1046–51.

    Article  PubMed  CAS  Google Scholar 

  12. Kennedy SH, McKenna KF, Baker GB. Monoamine oxidase inhibitors. In: Sadock BJ, Sadock VA, editors. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000. p. 2398–407.

    Google Scholar 

  13. Prozac (fluoxetine hydrochloride) Prescribing Information, Eli Lilly and Company, Indianapolis, IN, October 2009. http://www.prozac.com/Pages/index.aspx. Accessed on March 5, 2011.

  14. Durson SM, Mathew VM, Reveley MA. Toxic serotonin syndrome after fluoxetine plus carbamazepine. Lancet. 1993;342:442–3.

    Article  Google Scholar 

  15. Mekler G, Woggon B. A case of serotonin syndrome caused by venlafaxine and lithium. Pharmacopsychiatry. 1997;30:272–3.

    Article  PubMed  CAS  Google Scholar 

  16. Adan-Manes J, Novalbos J, Lopez-Rodriguez R, et al. Lithium and venlafaxine interaction: a case of serotonin syndrome. J Clin Pharm Ther. 2006;31:397–400.

    Article  PubMed  CAS  Google Scholar 

  17. Gillman PK. Serotonin syndrome: clomipramine too soon after moclobemide. Int Clin Psychopharmacol. 1997;12:339–42.

    Article  PubMed  CAS  Google Scholar 

  18. Fernandes C, Reddy P, Kessel B. Rasagiline-induced serotonin syndrome (letter to the editor). Mov Disord 10.1002/mds.23649.

  19. Toyama SC, Iacono RP. Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? Ann Pharmacother. 1994;28:405.

    PubMed  CAS  Google Scholar 

  20. Waters CH. Fluoxetine and selegiline–lack of significant interaction. Can J Neurol Sci. 1994;21:259–61.

    PubMed  CAS  Google Scholar 

  21. Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). American Psychiatric Association 2000.

    Google Scholar 

  22. Zyvox (linezolid) Prescribing Information, Pfizer, distributed by Pharmacia & Upjohn Company, NY, NY, June 2010. http://www.pfizer.com/products/rx/rx_product_zyvox.jsp. Accessed on March 5, 2011.

  23. Morales N, Vermette H. Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine. Psychosomatics. 2005;46:274–5.

    Article  PubMed  Google Scholar 

  24. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991;337:246.

    Article  PubMed  CAS  Google Scholar 

  25. Cymbalta (duloxetine hydrochloride) Prescribing Information, Eli Lilly and Company, Indianapolis, IN, April 22, 2011. http://www.cymbalta.com/index.jsp?WT.seg_1=Branded&DCSext.ag=BrandGeneral&WT.mc_id=CymDPNA14120001&WT.srch=1. Accessed on May 6, 2011.

  26. Savella (milnacipran hydrochloride) Prescribing Information, Forest Pharmaceuticals, Inc. January 2009. http://www.savella.com/index.aspx. Accessed on May 6, 2011.

  27. Yacoub HA, Johnson WG, Souayah N. Serotonin syndrome after administration of milnacipran for fibromyalgia. Neurology. 2010;74:699.

    Article  PubMed  Google Scholar 

  28. Parrott AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002;71:837–44.

    Article  PubMed  CAS  Google Scholar 

  29. Randall T. Ecstasy-fueled “rave” parties become dances of death for English youths. JAMA. 1992;268:1505–6.

    Article  PubMed  CAS  Google Scholar 

  30. Drugs and Chemicals of Concern: dextromethorphan. U.S. Department of Justice, Drug Enforcement Administration, Office of Diversion Control. Aug 2010. http://www.deadiversion.usdoj.gov/drugs_concern/dextro_m/dextro_m.htm.Accessed April 9, 2011.

  31. Substance Abuse and Mental Health Services Administration. Office of Applied Studies. The NSDUH report: misuse of over-the-counter cough and cold medications among persons aged 12 to 25. January 10, 2008. Available at http://www.oas.samhsa.gov/2k8/cough/cough.cfm. Accessed April 9, 2011.

  32. Ball, JK, Albright, V. Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Emergency department visits involving dextromethorphan. The New DAWN report 2006; 32:1. Available at http://www.oas.samhsa.gov/DAWN/dextromethorphan.cfm. Accessed April 10, 2011.

  33. Schwartz AR, Pizon AF, Brooks DE. Case series: dextromethorphan-induced serotonin syndrome. Clin Toxicol. 2008;46:771–3.

    Article  CAS  Google Scholar 

  34. Andersen IB. Dextromethorphan abuse in adolescence: a rising trend. California Poison Control System, 2007, slides accessed from www.csam-asam.org/pdf/misc/DXM_CSAM_9_07.ppt on April 10, 2011.

  35. Forget P, le Polain de Waroux B, Wallemacq P, et al. Life-threatening dextromethorphan intoxication associated with interaction with amitriptyline in a poor CYP2D6 metabolizer: a single case re-exposure study. J Pain Symptom Manage. 2008;36:92–6.

    Article  PubMed  CAS  Google Scholar 

  36. Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32:33–8.

    Article  PubMed  CAS  Google Scholar 

  37. Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. 1996;16:323–7.

    Article  PubMed  CAS  Google Scholar 

  38. Anon. US Food and Drug Administration. Information for healthcare professionals. Selective serotonin reuptake inhibitors (SSRIs), selective serotonin norepinephrine reuptake inhibitors (SNRIs), 5-hydroxytryptamine receptor agonists (triptans). 2006. Available at: http://www.fda.gov/cder/drug/InfoSheets/HCP/triptansHCP.htm.

  39. Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. 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;50:1089–99.

    Article  PubMed  Google Scholar 

  40. Ng BKW, Cameron AJD. The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics. 2010;51:194–200.

    PubMed  Google Scholar 

  41. DeSilva KE, Le Flore DB, Marston BJ, Rimland D. Serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine. AIDS. 2001;15:1281–5.

    Article  PubMed  CAS  Google Scholar 

  42. Gill M, Lo Vecchio F, Seldan B. Serotonin syndrome in a child after a single dose of fluvoxamine. Ann Emerg Med. 1999;33:457–9.

    Article  PubMed  CAS  Google Scholar 

  43. Spirko BA, James FW. Serotonin syndrome: a new pediatric intoxication. Pediatr Emerg Care. 1999;15:440–3.

    Article  PubMed  CAS  Google Scholar 

  44. Parker V, Wong AHC, Boon HS, Seeman MV. Adverse reactions to St John’s Wort. Can J Psychiatry. 2001;46:77–9.

    PubMed  CAS  Google Scholar 

  45. Nisijima K, Nibuya M, Kato S. Toxic serotonin syndrome successfully treated with electroconvulsive therapy. J Clin Psychopharmacol. 2002;22:338–9.

    Article  PubMed  Google Scholar 

  46. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112–20.

    Article  PubMed  CAS  Google Scholar 

  47. Graudins A, Stearman CB. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998;16:615–9.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medical Affairs, Boehringer-Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Road, Ridgefield, CT, 06877, USA

    Mark Forrest Gordon M.D.

  2. Neurological Specialties of Long Island, LLP, Great Neck, NY, USA

    Adena N. Leder D.O.

Authors
  1. Mark Forrest Gordon M.D.
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  2. Adena N. Leder D.O.
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Correspondence to Mark Forrest Gordon M.D. .

Editor information

Editors and Affiliations

  1. , Neurology, Columbia University Medical Center, West 168th St. Suite 310 710, New York, 10032, USA

    Steven J. Frucht

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Movement_Disorders_Emergencies_C18.mov (33,839 KB)

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Gordon, M.F., Leder, A.N. (2013). Serotonin Syndrome. In: Frucht, S. (eds) Movement Disorder Emergencies. Current Clinical Neurology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-835-5_18

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  • DOI: https://doi.org/10.1007/978-1-60761-835-5_18

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-834-8

  • Online ISBN: 978-1-60761-835-5

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