Neurol. praxi. 2024;25(2):135-145 | DOI: 10.36290/neu.2023.052

Serotonin syndrome and pain therapy

MUDr. Jan Procházka
Centrum léčby chronické bolesti při KAPIM KZ, a. s., Masarykova nemocnice Ústí nad Labem

Serotonin syndrome is a potentially life-threatening drug-induced toxidrome associated with increased serotonergic activity in both the peripheral and central nervous systems. It is characterized by a broad spectrum of clinical findings, which include mental state changes, autonomic instability, and hyperexcitability of CNS with neuromuscular abnormalities. Serotonin syndrome can arise usually by simultaneous administrations of 2 or more serotoninergic drugs, the combination including monoamine oxidase inhibitors is especially dangerous, but occurrence in monotherapy is also possible. This review describes pathophysiology and clinical manifestation of this syndrome and the drugs at risk, with a particular focus on drugs used in the treatment of chronic pain.

Keywords: serotonin syndrome, serotoninergic drugs, cytochrome P450, analgesics.

Received: June 29, 2023; Revised: June 30, 2023; Accepted: August 9, 2023; Prepublished online: August 9, 2023; Published: April 16, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Procházka J. Serotonin syndrome and pain therapy. Neurol. praxi. 2024;25(2):135-145. doi: 10.36290/neu.2023.052.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Ailawadhi S, Sung K­‑W, Carlson LA, Baer MR: Serotonin syndrome cyused by interaction between citalopram and fentanyl. J Clin Pharmacoy Therap. 2007;32:199-202. Go to original source... Go to PubMed...
    2. Ansari H, Kouti L. Drug interaction and serotonin toxicity with opioid use: another reason to avoid opioids in headache and migraine treatment. Curr Pain Headache Rep. 2016;20:60. doi: 10.1007/c11916-016-1579-3. Go to original source...
    3. Baldo BA. Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects. Arch Toxicol. 2018; https://doi.org/10.1007/s00204-018-2244-6. Go to original source... Go to PubMed...
    4. Baldo BA, Rose MA. The anaestetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review. Brit J Anaesth. 2020;124(1):44-62. Go to original source... Go to PubMed...
    5. Baldo BA. Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity serotonin toxicity. Arch Toxicol. 2021; https://doi.org/10.1007/s00204-021-03068-2. Go to original source... Go to PubMed...
    6. Barann M, Stamer UM, Lyutenska M, et al. Effects of opioids on human serotonin transporters. Naunyn­‑Schmiedaberg's Arch Pharmacol. 2015;388:43-49. Go to original source... Go to PubMed...
    7. Bates D, Schultheis BC, Hanes MC, et al. A comprehensive algorithm for management of neuropathic pain. Pain Med. 2019;20:S2-S12. Go to original source... Go to PubMed...
    8. Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Phys. 2015;18:395-400. Go to original source...
    9. Boyer EW, Shannon M. The Serotonin syndrome. N Engl J Med. 2005;352:1112-20. Go to original source... Go to PubMed...
    10. Dizdarevic A, Bremer N. Cervical spinal cord stimulation with concomitant serotonin norepinephrine reuptake inhibitor therapy leading to the serotonin syndrome. Pain Med. 2017;18:1199-1202. Go to original source... Go to PubMed...
    11. Duma SR, Fung VSC. Drug­‑induced movement disorders. Aust Prescr. 2019;42:56-61. Go to original source... Go to PubMed...
    12. Dunkley EJC, Isbister GK, Sibbritt D, et al. The Hunter serotonin toxicity criteria: sinple and accurate diagnostic decision rules for serotonin toxicity. Q J Med. 2003;96:635-42. Go to original source... Go to PubMed...
    13. FDA Drug safety communications. FDA warns about several safety issues with opioid pain medicines; requires label changes. March 22, 2016. https ://www.fda.gov/downl oads/Drugs /DrugSafety /UCM49 1302.pdf.
    14. Foong AL, Grindrod KA, Patel T, Kellar J. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Phys. 2018;64(10):720-727.
    15. Francescangeli J, Karamchandani K, Powell M, Bonavia A. The serotonin syndrome: from molecular mechanisms to clinical practice. Int J Molecul Sci. 2019;20:2288. doi:10.3390/ijms20092288 Go to original source... Go to PubMed...
    16. Fujáková M, Kopeček M. Antidepresiva - od teorie ke klinické praxi. Klin Farmakol Farm. 2012;26(1):29-37.
    17. Gayle JA, Abadie JV, Kaye AM, Kaye AD. Serotonin syndrome. In: A.D. Kaye et al. (eds.), Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care. Springer Science+Business Media New York. 2015:797-807. doi: 10.1007/978-1-4614-8948-1_49. Go to original source...
    18. Gressler LE, Hammond DA, Painter JT. Serotonin syndrome in tapentadol literature: systematic review of original research. J Pain Palliat Care Pharmacotherapy. 2017;31(3-4):228-236. Go to original source... Go to PubMed...
    19. Höschl C. Neurotrofní účinky antidepresiv. Available from: http://www.hoschl.cz/files/445_cz_Neurotrofni%20AD.pdf.
    20. Jones D, Story DA. Serotonin syndrome and the anaesthetist. Anaesth Intensive Care. 2005;33:181-87. Go to original source... Go to PubMed...
    21. Kanova K, Kohout P. Serotonin - its synthesis and roles in the healthy and the critically ill. Int J Med Sci. 2021;22:4873. Go to original source... Go to PubMed...
    22. Koury KM, Tsui B, Gulur P. Incidence of serotonine syndrome in patients treated with fentanyl on serotoninergic agents. Pain Phys. 2015;18:E27-E30. Go to original source...
    23. Malcolm B, Thomas K. Serotonin toxicity of serotoninergic psychedelics. Psychopharmacology. 2022;239(6):1881-1891. Go to original source... Go to PubMed...
    24. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine. 2000;79(4):201-209. Go to original source... Go to PubMed...
    25. Mastroianni A, Ravaglia G. Serotonin syndrome due to co­‑administration of linezolid and methadone. Infez Med. 2017;25(3):263-66.
    26. Mohr P. Serotoninový syndrom - diagnostika, terapie, prevence. Psych Praxi. 2001;3:117-20.
    27. Nelson EM, Philbrick AM: Avoiding serotonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother. 2012;46:1712-16. Go to original source... Go to PubMed...
    28. Prakash S, Adroja B, Parekh H. Serotonin syndrome in patients with headache disorders. BMJ Case Rep. 2017. doi:10.1136/bcr-2017-221383. Go to original source... Go to PubMed...
    29. Prakash S, Rathore C, Rana K, Patel H. Antiepileptic drugs and serotonin syndrome - a systematic review of case series and case reports. Seizure Eur J Epil. 2021;91:117-31. Go to original source... Go to PubMed...
    30. Praško J, Prašková H. Farmakoterapie deprese. Psychiat. Praxi. 2006;5:214-224.
    31. Prokeš M, Suchopár J. Serotoninový syndrom: co bychom o něm měli vědět. Med Praxi. 2014;11(5):226-230.
    32. Rastogi R, Swarm RA, Patel TA. Case scenarion: opioid assiciation with serotonin syndrome. Implications to the practitioners. Anesthesiology. 2011;115(6):1291-98. Go to original source... Go to PubMed...
    33. Rickli A, Liakoni E, Hoener MC, Liechti ME. Opioid­‑induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome. Brit J Prarmacol. 2018;175:532-543. Go to original source... Go to PubMed...
    34. Roulet L, Rollason V, Desmeules J, Piguet V. Tapentadol versus tramadol: a narrative and comparative review of ther pharmacological, efficacy and safety profiles in adult patients. Drugs. 2021;81:1257-72. Go to original source... Go to PubMed...
    35. Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin syndrome: patophysiology, clinical features, management, and potential ruture directions. Int J Tryptoph Res. 2019;12(1):1-14. Go to original source... Go to PubMed...
    36. Shelton RC. Serotonin and norepinephrine reuptake inhibitors. Handbook of Experimental Pharmacology, Springer Nature Switzerland AG 2018. Available from: https://doi.org/10.1007/164_2018_164. Go to original source... Go to PubMed...
    37. Spadaro A, Scott KR, Koyfman A, Long B. High risk and low prevalence disease: serotonin syndrome. Am J Emerg Med. 2022;61:90-97. Go to original source... Go to PubMed...
    38. SPC: Peritol 4 mg https://www.sukl.cz/modules/medication/detail.php?code=0219901 & tab=texts.
    39. Tašková I. Úzkostné poruchy a jejich léčba. Prakt Lékáren. 2021;17(4):207-212. Go to original source...
    40. Tormoehlen LM, Rusyniak DE. Neuroleptic malignant syndrome and serotonin syndrome. In: Romanovsky AA: Handbook of clinical neurology, 3rd Series, Elsevier 2018:663-675. Go to original source...
    41. UpToDate 2023. Available from: https://www.uptodate.com/contents/image?imageKey=EM%2F71268.
    42. Vaněk J. Serotoninový syndrom - častý problém, či vzácná komplikace? Prakt. Lékáren. 2022;18(2):75-78. Go to original source...
    43. Vojtíšek P, Nalos D. Serotoninergní syndrom - kazuistika. Anest Intenziv Mad. 2011;22(3):159-162.
    44. Werneke U, Truedson­‑Martiniussen P, Wikström H, Ott M. Serotonin syndrome: a clinical review of current controversies. J Integr Neurosci. 2020;19(4):719-727. Go to original source... Go to PubMed...
    45. Zakharov S. Toxikologie nových rekreačních drog. Available from: https://postudium.cz/mod/book/view.php?id=1243 & chapterid=522.

    Return to the content


    Neurology for Practice

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.