Abstract
Serotonin syndrome is a life-threatening condition caused by medications that affect serotonin metabolism or that act as direct agonists
for serotonin receptor or a combination of both. The syndrome gives rise to a variety of mental, autonomic, and neuromuscular
manifestations, which can range from mild to life-threatening. We report a clinical case of a patient who developed this syndrome due to
the co-administration and synergism of linezolid and fentanyl, with a wide variety of clinical characteristics, from the most subtle, such as
high blood pressure levels difficult to manage while under the effect of sedoanalgesia, to the most florid manifestations of the syndrome
after 48 hours of its suspension. The association of these drugs represents a poorly reported etiology that may favor the appearance of
the syndrome, while the use of benzodiazepines may mask the condition, making its diagnosis difficult. MÉD.UIS.2020;33(3): 59-66
References
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0.1097/JCP.0000000000000751.
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10. Nguyen CT, Xie L, Alley S, McCarron RM, Baser O, Wang Z. Epidemiology and economic burden of serotonin syndrome with
concomitant use of serotonergic agents: A retrospective study utilizing two large US claims databases. Prim Care Companion CNS Disorder. 2017;19(6).
11. Watson WA, Litovitz TL, Klein-Schwartz W, Rodgers GC, Reid N, Youniss J, et al. 2004 Annual Report of the American Association of Poison
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12. Watson WA, Litovitz TL, Rodgers GC Jr, Klein-Schawartz, Youniss J, Rose SR. 2002 Annual Report of the American Association of
Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2003;21(5):353-421.
13. Gummin DD, Mowry JB, Spyker DA, Brooks DE, Fraser MO, Banner W. Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th annual report. Clin Toxicol. 2017;55(10):1072-1252.
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15. Werneke U, Jamshidi F, Taylor D, Ott M. Conundrums in neurology: diagnosing serotonin syndrome – a meta-analysis of cases. BMC Neurol. 2016;16:97.
16. Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49(448):871-874.
17. Francescangeli J, Karamchandani K, Powell M, Bonavia A. The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice. Int J Mol Sci. 2019;20(9):2288.
18. Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotoninergic disorders. Am
Acad of Pain Med. 2003; 4(1): 63-74.
19. 19. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533‐540.
20. Dosi R, Ambaliya A, Joshi H, Patell R. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep. 2014;2014(1):bcr2014204154.
21. Mills KC. Serotonin syndrome. A clinical update. Crit Care Clin. 1997;13(4):763-783.
22. Dunkley EJC, 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(9):635-642.
23. Boyer EW, Traub SJ, Grayzel J. Serotonin Syndrome. In: UpToDate, Waltham, MA, 2010.
24. Lawrence K, Adra M, Gillman P. Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing Data. Clin Infect Dis. 2006;42(11), 1578–1583.
25. Mandell L, Bennett E, Dolin R: Principles and Practice of Infectious Diseases, 5th edition. Churchill Livingstone, Inc. 2000. pp. 392–393.
26. Samartzis L, Savvari P, Kontogiannis S, Dimopoulos S. Linezolid Is Associated with Serotonin Syndrome in a Patient Receiving Amitriptyline, and Fentanyl: A Case Report and Review of the Literature. Case Rep Psychiatry. 2013;2013(3): 617251.
27. Frank, Christopher. Recognition and treatment of serotonin syndrome. Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008;54(7):988-992.
28. Bronstein A, Spyker D, Cantilena L, Rumack B, Dart R. Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 29th Annual Report. Clin Toxicol (Phila). 2012; 50(10): 911 – 1164.
29. Rubinstein E, Isturiz R, Standiford HC, Smith LG, Oliphant TH, Cammarata S et al. Worldwide assessment of linezolid’s clinical safety and tolerability: comparator-controlled phase III studies. Antimicrob Agents Chemother. 2003;47(6):1824–1831.
30. Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43(2):180–187. 31.
homas CR, Rosenberg M, Blythe V, et al. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry. 2004;43(7):790.
32. Taylor JJ, Estes LL, Wilson JW. Linezolid and serotonergic drug interactions. Clin Infect Dis. 2006;43(2):180–187.
33. Strouse TB, Kerrihard TN, Forscher CA, et al. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol. 2006;26(6):681–683.
34. Quinn DK, Stern TA. Linezolid and serotonin syndrome. Prim Care Companion J Clin Psychiatry. 2009;11(6):353-356.
35. Ramsay R, Dunford C, Gillman P. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152(6): 946 - 951.
36. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. CMAJ. 2003;168(11):1439-1442.
37. Young P, Finn BC, Pellegrini D, Soloaga ED, Bruetman JE. Tormenta simpatica paroxistica siguiendo a injuria axonal difusa. Medicina (B.
ires). 2006;66(5): 439-42.
2. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore) [Internet]. 2000 Jul;79(4):201-9. Disponible en: 10.1097/00005792-200007000-00001.
3. Jurek L, Nourredine M, Megarbane B, d’Amato T, Dorey JM, Rolland B. The serotonin syndrome: An updated literature review. Rev Med Interne [Internet]. 2019 Feb;40(2):98-104. Disponible en: 10.1016/j.revmed.2018.08.010.
4. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med [Internet]. 2005 Mar 17;352(11): 1112-20. Disponible en: 10.1056/ NEJMra041867.
5. Bartlett D. Drug-Induced Serotonin Syndrome. Crit Care Nurse [Internet]. 2017 Feb;37(1):49-54. Disponible en: 10.4037/ ccn2017169.
6. Karkow DC, Kauer JF, Ernst EJ. Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy. J Clin Psychopharmacol [Internet]. 2017 Oct;37(5):518–23. Disponible en:
0.1097/JCP.0000000000000751.
7. Foong AL, Grindrod KA, Patel T, Kellar J. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician. 2018;64(10):720-27
8. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148(6):705-13
9. Mojtabai R, Olfson M. National trends in long-term use of antidepressant medications. J Clin Psychiatry. 2014;75(2):169-177.
10. Nguyen CT, Xie L, Alley S, McCarron RM, Baser O, Wang Z. Epidemiology and economic burden of serotonin syndrome with
concomitant use of serotonergic agents: A retrospective study utilizing two large US claims databases. Prim Care Companion CNS Disorder. 2017;19(6).
11. Watson WA, Litovitz TL, Klein-Schwartz W, Rodgers GC, Reid N, Youniss J, et al. 2004 Annual Report of the American Association of Poison
ontrol Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2005;23(5):589-666.
12. Watson WA, Litovitz TL, Rodgers GC Jr, Klein-Schawartz, Youniss J, Rose SR. 2002 Annual Report of the American Association of
Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2003;21(5):353-421.
13. Gummin DD, Mowry JB, Spyker DA, Brooks DE, Fraser MO, Banner W. Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th annual report. Clin Toxicol. 2017;55(10):1072-1252.
14. Isbister G, Buckley N. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28(5):205-14
15. Werneke U, Jamshidi F, Taylor D, Ott M. Conundrums in neurology: diagnosing serotonin syndrome – a meta-analysis of cases. BMC Neurol. 2016;16:97.
16. Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49(448):871-874.
17. Francescangeli J, Karamchandani K, Powell M, Bonavia A. The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice. Int J Mol Sci. 2019;20(9):2288.
18. Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotoninergic disorders. Am
Acad of Pain Med. 2003; 4(1): 63-74.
19. 19. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533‐540.
20. Dosi R, Ambaliya A, Joshi H, Patell R. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep. 2014;2014(1):bcr2014204154.
21. Mills KC. Serotonin syndrome. A clinical update. Crit Care Clin. 1997;13(4):763-783.
22. Dunkley EJC, 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(9):635-642.
23. Boyer EW, Traub SJ, Grayzel J. Serotonin Syndrome. In: UpToDate, Waltham, MA, 2010.
24. Lawrence K, Adra M, Gillman P. Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing Data. Clin Infect Dis. 2006;42(11), 1578–1583.
25. Mandell L, Bennett E, Dolin R: Principles and Practice of Infectious Diseases, 5th edition. Churchill Livingstone, Inc. 2000. pp. 392–393.
26. Samartzis L, Savvari P, Kontogiannis S, Dimopoulos S. Linezolid Is Associated with Serotonin Syndrome in a Patient Receiving Amitriptyline, and Fentanyl: A Case Report and Review of the Literature. Case Rep Psychiatry. 2013;2013(3): 617251.
27. Frank, Christopher. Recognition and treatment of serotonin syndrome. Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008;54(7):988-992.
28. Bronstein A, Spyker D, Cantilena L, Rumack B, Dart R. Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 29th Annual Report. Clin Toxicol (Phila). 2012; 50(10): 911 – 1164.
29. Rubinstein E, Isturiz R, Standiford HC, Smith LG, Oliphant TH, Cammarata S et al. Worldwide assessment of linezolid’s clinical safety and tolerability: comparator-controlled phase III studies. Antimicrob Agents Chemother. 2003;47(6):1824–1831.
30. Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43(2):180–187. 31.
homas CR, Rosenberg M, Blythe V, et al. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry. 2004;43(7):790.
32. Taylor JJ, Estes LL, Wilson JW. Linezolid and serotonergic drug interactions. Clin Infect Dis. 2006;43(2):180–187.
33. Strouse TB, Kerrihard TN, Forscher CA, et al. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol. 2006;26(6):681–683.
34. Quinn DK, Stern TA. Linezolid and serotonin syndrome. Prim Care Companion J Clin Psychiatry. 2009;11(6):353-356.
35. Ramsay R, Dunford C, Gillman P. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152(6): 946 - 951.
36. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. CMAJ. 2003;168(11):1439-1442.
37. Young P, Finn BC, Pellegrini D, Soloaga ED, Bruetman JE. Tormenta simpatica paroxistica siguiendo a injuria axonal difusa. Medicina (B.
ires). 2006;66(5): 439-42.
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