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P-036 - Tramadol for Pain Management Associated with Serotonin Syndrome

POSTER ABSTRACT
Location:  Exhibit Hall

    Author/Presenter(s)

  • AT

    Anisha M. Thomas, n/a

    Medical Student
    Touro University California College of Osteopathic Medicine
    Vallejo, California

  • AL

    Angela C. Lu, n/a

    Medical Student
    Touro University California College of Osteopathic Medicine
    Walnut Creek, California

  • KL

    Kyaw Lin, D.O.

    Interventional Pain Physician
    Touro University California - College of Osteopathic Medicine
    Vallejo, California

Abstract Title: Tramadol for Pain Management Associated with Serotonin Syndrome

Background: Serotonin syndrome is a condition caused by excessive serotonergic activity, resulting in altered neuromuscular activity, autonomic processing, and mental status.1 Though often associated with antidepressants, recent literature shows increasing reports of serotonin syndrome from drug-drug interactions between tramadol and serotonergic medications.2 Compared to other opiates, tramadol is an analgesic agent prescribed for its decreased potential for addiction and more favorable side effects.2,3 However, since the drug acts as a central opiate agonist and norepinephrine and serotonin reuptake inhibitor, the drug poses an increased risk for serotonin syndrome.2 This report presents a case in which tramadol and concurrent serotonergic medications resulted in symptoms associated with serotonin syndrome.



A 63-year-old male presents to the emergency department with worsening axial low back pain and a history of anxiety and depression. Lumbar spine MRI suggests L2/L3 discitis. In addition to current medications of sertraline 100 mg BID and quetiapine 300 mg QHS, the patient began a pain regimen of gabapentin 100 mg BID and acetaminophen 325 mg Q6H PRN for mild pain, tramadol 50 mg Q4H PRN for moderate pain, and hydrocodone-acetaminophen 5-325 mg Q4H PRN for severe pain. The patient reported feeling anxious, shaken, and “crazy” on tramadol.

Purpose/Objectives: In this case study, the focus is on managing a patient presenting with multiple chronic medical conditions, including diabetes, chronic obstructive pulmonary disorder (COPD), hypertension, and chronic pain. The study brings attention to the potential occurrence of serotonin syndrome as a result of the interaction between sertraline, quetiapine, and tramadol. It underscores the importance of sound clinical decision-making and strategies to minimize harmful drug interactions. This clinical scenario emphasizes the significance of careful drug management for elderly patients with polypharmacy and comorbidities to improve the quality of care.

Methods: The management plan for this patient was aimed at avoiding serotonin syndrome. His medication regimen re-review was conducted to identify the serotonergic drug(s) and drug interactions. Acetaminophen intake was also monitored to avoid exceeding the recommended daily maximum dose since high-dose acetaminophen can precipitate liver toxicity and negatively affect patient outcomes.4



The initiative focused on educating patients to recognize and promptly report signs and symptoms of serotonin syndrome, with an emphasis on early detection and monitoring for timely care. Lastly, a multidisciplinary approach to the case made it possible to guarantee that intervention and treatment plans were in place for the patient's total comprehensive care as well as for diagnosing and avoiding serotonin syndrome.


Results: As a result of similar symptoms of anxiety and shakiness after each administration of tramadol, hydrocodone-acetaminophen was recommended for this patient over the usage of tramadol. This recommendation was made based on multiple areas of concern. First, drug-drug interactions between tramadol, sertraline, and quetiapine were noted to increase serotonin in the central nervous system and therefore increase the risk of serotonin syndrome.2,5 Tramadol’s dual mechanism of action contributes to this increased likelihood of serotonin syndrome due to the drug not only binding to μ-receptors and acting as an opioid analgesic but also blocking the reuptake of monoamines, such as serotonin and norepinephrine.2 In addition, both hydrocodone-acetaminophen 5-325 mg and tramadol 50 mg equaled 10 morphine milligram equivalents (MME), indicating the patient received equivalent amounts of MME from both medications despite tramadol’s prescription for moderate pain and hydrocodone-acetaminophen’s prescription for severe pain. Discontinuation of tramadol was suggested due to the above concerns.



During the follow-up period, there were no signs of serotonin syndrome in the patient after discontinuing tramadol 50 mg and adjusting medication to hydrocodone-acetaminophen 5-325 mg for 3-5 days. This signified a reduced risk of serotonin syndrome, ensured the patient’s safety, and indicated that the care given would produce the best possible treatment outcome.

Conclusions/Implications for future research and/or clinical care: The management approach for the 63-year-old male patient focused on prevention of serotonin syndrome—a potentially life-threatening condition due to medication interaction. This included a critical review of his medication list for serotonergic drug interactions. The recommendation for discontinuing tramadol, a serotonergic agent, and substitution with hydrocodone-acetaminophen 5-325 mg, a drug with lower risk, was an important preventive measure.6 Monitoring of acetaminophen intake was stressed to avoid exceeding the recommended daily limit which could potentiate negative health outcomes.


Patient education was an integral part of ensuring vigilance for the signs and symptoms of serotonin syndrome and reporting with urgency if adversities appear to institute early interventions when required.7 Collaboration among interdisciplinary teams helped institute preventive measures and assured all-around care. Strategies were aimed at protecting the patient, minimizing the risk of developing serotonin syndrome, and maximizing the safety and efficacy of his prescribed drug therapy.

References:


  1. Takeshita, Junji, and Mark H. Litzinger. “Serotonin syndrome associated with Tramadol.” The Primary Care Companion to The Journal of Clinical Psychiatry, vol. 11, no. 5, 15 Oct. 2009, https://doi.org/10.4088/pcc.08l00690.



  2. Kaye, Adam, et al. “Tramadol, pharmacology, Side Effects, and serotonin syndrome: A Review.” July 2015, 14 July 2015, https://doi.org/10.36076/ppj.2015/18/395.



  3. Thiels, Cornelius A, et al. “Chronic use of Tramadol after acute pain episode: Cohort study.” BMJ, 14 May 2019, https://doi.org/10.1136/bmj.l1849.



  4. Perananthan, V., Buckley, N., & NPS MedicineWise. (2021). Opioids and antidepressants: which combinations to avoid. In Australian Prescriber (Vol. 44, Issue 2). https://www.nps.org.au/assets/AP/pdf/p41-Perananthan-Buckley.pdf



  5. Miyamatsu, Yayoi, and Ryutaro Tanizaki. “Serotonin syndrome triggered by increasing the dose of quetiapine.” Clinical Practice and Cases in Emergency Medicine, vol. 5, no. 3, 5 Aug. 2021, pp. 365–366, https://doi.org/10.5811/cpcem.2021.5.52505.



  6. Ayub, Zunaira. “Transient serotonin syndrome caused by concurrent use of Tramadol and selective serotonin reuptake inhibitor.” American Journal of Case Reports, vol. 15, 2014, pp. 562–564, https://doi.org/10.12659/ajcr.892264.


  7. Rastogi, Rahul, et al. “Case scenario: Opioid association with serotonin syndrome.” Anesthesiology, vol. 115, no. 6, 1 Dec. 2011, pp. 1291–1298, https://doi.org/10.1097/aln.0b013e31823940c0.