Advertisement

Serotonin Syndrome

  • Mark Forrest GordonEmail author
  • Adena N. Leder
Chapter
Part of the Current Clinical Neurology book series (CCNEU)

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.

Keywords

Methylene Blue Neuroleptic Malignant Syndrome Serotonin Syndrome Serotonergic Neuron Serotonergic Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

Movement_Disorders_Emergencies_C18.mov (33,839 KB)

References

  1. 1.
    Oates JA, Sjoerdsma A. Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurology. 1960;10:1076–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Mills KC. Serotonin syndrome. Am Fam Physician. 1995;52:1475–82.PubMedGoogle Scholar
  3. 3.
    Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705–13.PubMedGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 5.
    Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. Med J Aust. 2007;187:361–5.PubMedGoogle Scholar
  6. 6.
    Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008;7:587–96.PubMedCrossRefGoogle Scholar
  7. 7.
    Gillman PK. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache. 2010;50:264–72.PubMedCrossRefGoogle Scholar
  8. 8.
    Mohammad-Zadeh LF, Moses L, Gwaltney-Brant SM. Serotonin: a review. J Vet Pharmacol Therap. 2008;31:187–99.CrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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. 11.
    Gillman PK. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry. 2006;59:1046–51.PubMedCrossRefGoogle Scholar
  12. 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. 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. 14.
    Durson SM, Mathew VM, Reveley MA. Toxic serotonin syndrome after fluoxetine plus carbamazepine. Lancet. 1993;342:442–3.CrossRefGoogle Scholar
  15. 15.
    Mekler G, Woggon B. A case of serotonin syndrome caused by venlafaxine and lithium. Pharmacopsychiatry. 1997;30:272–3.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Gillman PK. Serotonin syndrome: clomipramine too soon after moclobemide. Int Clin Psychopharmacol. 1997;12:339–42.PubMedCrossRefGoogle Scholar
  18. 18.
    Fernandes C, Reddy P, Kessel B. Rasagiline-induced serotonin syndrome (letter to the editor). Mov Disord  10.1002/mds.23649.
  19. 19.
    Toyama SC, Iacono RP. Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? Ann Pharmacother. 1994;28:405.PubMedGoogle Scholar
  20. 20.
    Waters CH. Fluoxetine and selegiline–lack of significant interaction. Can J Neurol Sci. 1994;21:259–61.PubMedGoogle Scholar
  21. 21.
    Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). American Psychiatric Association 2000.Google Scholar
  22. 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. 23.
    Morales N, Vermette H. Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine. Psychosomatics. 2005;46:274–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991;337:246.PubMedCrossRefGoogle Scholar
  25. 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. 26.
    Savella (milnacipran hydrochloride) Prescribing Information, Forest Pharmaceuticals, Inc. January 2009. http://www.savella.com/index.aspx. Accessed on May 6, 2011.
  27. 27.
    Yacoub HA, Johnson WG, Souayah N. Serotonin syndrome after administration of milnacipran for fibromyalgia. Neurology. 2010;74:699.PubMedCrossRefGoogle Scholar
  28. 28.
    Parrott AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002;71:837–44.PubMedCrossRefGoogle Scholar
  29. 29.
    Randall T. Ecstasy-fueled “rave” parties become dances of death for English youths. JAMA. 1992;268:1505–6.PubMedCrossRefGoogle Scholar
  30. 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. 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. 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. 33.
    Schwartz AR, Pizon AF, Brooks DE. Case series: dextromethorphan-induced serotonin syndrome. Clin Toxicol. 2008;46:771–3.CrossRefGoogle Scholar
  34. 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. 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.PubMedCrossRefGoogle Scholar
  36. 36.
    Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32:33–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. 1996;16:323–7.PubMedCrossRefGoogle Scholar
  38. 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. 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.PubMedCrossRefGoogle Scholar
  40. 40.
    Ng BKW, Cameron AJD. The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics. 2010;51:194–200.PubMedGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Spirko BA, James FW. Serotonin syndrome: a new pediatric intoxication. Pediatr Emerg Care. 1999;15:440–3.PubMedCrossRefGoogle Scholar
  44. 44.
    Parker V, Wong AHC, Boon HS, Seeman MV. Adverse reactions to St John’s Wort. Can J Psychiatry. 2001;46:77–9.PubMedGoogle Scholar
  45. 45.
    Nisijima K, Nibuya M, Kato S. Toxic serotonin syndrome successfully treated with electroconvulsive therapy. J Clin Psychopharmacol. 2002;22:338–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Graudins A, Stearman CB. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998;16:615–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Medical AffairsBoehringer-Ingelheim Pharmaceuticals, IncRidgefieldUSA
  2. 2.Neurological Specialties of Long Island, LLPGreat NeckUSA

Personalised recommendations