Tramadol-Induced Seizures in an Elderly Patient Without Comorbidities: A Case Report

Tramadol-Induced Seizures in an Elderly Patient Without Comorbidities: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Tramadol-Induced Seizures in an Elderly Patient Without Comorbidities: A Case Report Huda Farid Al Akrabi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7837568/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Tramadol is a widely used analgesic for moderate to severe pain due to its dual mechanism of µ-opioid receptor agonism and monoaminergic reuptake inhibition. While generally perceived as safe, it has been increasingly associated with neurotoxic side effects, particularly seizures. These adverse effects are commonly reported in patients with epilepsy, polypharmacy, or organ dysfunction. However, seizure events in elderly individuals without known risk factors are rare and underreported. Case Presentation: We describe a 72-year-old woman with no prior medical history who developed a generalized tonic-clonic seizure after administration of tramadol for an upper respiratory tract infection. She had received three therapeutic doses of tramadol. Her laboratory investigations and neuroimaging were unremarkable. Following withdrawal of the drug, the patient made a full recovery with no further seizure activity. Discussion Elderly patients are particularly vulnerable to adverse drug reactions due to altered pharmacokinetics and pharmacodynamics associated with aging. This case highlights the potential for tramadol to induce seizures even in the absence of predisposing comorbidities or drug interactions. Clinicians should be vigilant when prescribing tramadol to older individuals and should consider alternatives for pain control. Conclusion Tramadol should be prescribed with caution in elderly populations, regardless of apparent baseline health. Clinician awareness of tramadol’s seizure risk even at therapeutic doses is essential to patient safety. Neurology Clinical Pharmacology Geriatrics & Gerontology Tramadol Seizures Elderly Azithromycin Case Report Introduction Tramadol, a synthetic opioid analgesic, is commonly prescribed for moderate to moderately severe pain. Its widespread use in both hospital and outpatient settings stems from its dual mechanism of action: weak µ-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake. Tramadol is widely utilized in clinical settings due to its dual mechanism of action: µ-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake. Despite being considered relatively safe, it is increasingly implicated in neurotoxicity, particularly seizures. The risk is well-documented in patients with epilepsy, renal or hepatic dysfunction, and those using interacting medications. However, seizures in healthy individuals, especially the elderly, receiving therapeutic doses are rare but clinically significant. In low-resource settings, tramadol is frequently prescribed without comprehensive patient screening, making understanding its adverse profile critical. With global aging populations, the number of elderly individuals exposed to this drug is increasing. Unfortunately, this group is often underrepresented in clinical trials. Age-associated changes in drug metabolism and blood-brain barrier permeability may predispose to adverse neurological outcomes. One of the less frequently anticipated adverse effects of tramadol is seizure activity. Although seizures are typically associated with high doses or predisposing conditions—such as epilepsy, renal or hepatic impairment, or concurrent use of serotonergic drugs—there is emerging evidence of seizure occurrences even in healthy individuals receiving standard doses. The mechanisms underpinning these events involve increased excitatory neurotransmitter activity and impaired inhibitory GABAergic signaling. Elderly patients represent a high-risk group for drug-induced neurotoxicity. Age-related changes such as decreased renal and hepatic clearance, altered blood-brain barrier permeability, and polypharmacy increase susceptibility to adverse drug reactions. Unfortunately, elderly individuals are often underrepresented in clinical trials, leading to an underappreciation of risks associated with medications like tramadol. In this report, we describe a case of tramadol-induced seizure in an elderly patient without prior comorbidities. We explore possible pathophysiological mechanisms, review existing literature on similar cases, and highlight the importance of cautious prescribing practices in this population. This case aims to alert clinicians to this hidden danger and support safer prescribing practices. Finally, this report advocates for incorporating seizure risk assessments in routine prescribing practices and improving awareness among healthcare providers, especially in primary care settings. Educating patients and families about early signs of neurotoxicity and ensuring prompt medical attention can mitigate adverse outcomes. Case Presentation A 72-year-old female with no past medical history presented to the outpatient clinic with a 4 day history of sore throat, mild cough, and low-grade fever. She was diagnosed with an upper respiratory tract infection and prescribed azithromycin 500 mg once daily and tramadol 50 mg three times daily for symptomatic relief. After the third dose of tramadol, the patient experienced a sudden-onset generalized tonic-clonic seizure lasting approximately one minute. She was brought to the emergency department, where she was post-ictal but hemodynamically stable. Clinical examination was unremarkable. Laboratory investigations including complete blood count, electrolytes, renal and liver function tests were within normal limits. A non-contrast CT scan of the brain showed no acute intracranial pathology. Tramadol was discontinued immediately. No antiepileptic drugs were initiated. The patient showed progressive clinical improvement and had no further seizure episodes. She was discharged in stable condition with advice to avoid tramadol and follow up with her primary care physician. Discussion This case illustrates a rare but clinically significant adverse event tramadol induced seizures in an elderly patient without any known risk factors or comorbid conditions. Tramadol exerts analgesic effects through µ-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake. These mechanisms, particularly the serotonergic component, are implicated in seizure activity. While seizures have been associated with high doses, concomitant serotonergic drugs, renal/hepatic impairment, or epilepsy, our patient had none of these contributing factors. Few case reports have described similar occurrences in elderly individuals taking standard therapeutic doses without interacting medications. This suggests that age-related changes in neurophysiology or pharmacokinetics may increase susceptibility, even in seemingly low-risk patients. Recent pharmacovigilance data [ 1 , 2 ] suggest tramadol-related seizures may be underreported, especially in sub-Saharan African settings where access to diagnostic tools such as EEG or MRI is limited [ 1 , 2 ]. This raises concern for broader undetected incidence in vulnerable populations. Furthermore, a growing body of literature has demonstrated that tramadol, even when administered at therapeutic doses, may cause dose-independent seizures [ 3 , 4 ] in susceptible individuals [ 3 , 4 ]. Genetic polymorphisms, such as variations in CYP2D6 enzyme activity [ 5 ], may contribute to this phenomenon by altering metabolism of tramadol to its active metabolite, O-desmethyltramadol [ 5 ]. Clinicians should also be aware of the potential interaction between tramadol and other antibiotics like azithromycin, which may increase seizure susceptibility through indirect pathways such as hepatic enzyme competition or prolonged QT [ 6 ] interval [ 6 ]. Although a direct causal relationship is not well-established, caution is advisable. The need for regional pharmacovigilance programs and increased education about tramadol's seizure risk is particularly important in primary care and rural settings [ 7 , 8 ]. Patient safety could be improved with mandatory risk disclosure during prescribing and standardized screening for elderly patients [ 7 , 8 ]. This case aligns with existing reports that caution against the liberal use of tramadol, especially among the elderly. More extensive post-marketing surveillance and pharmacovigilance are required to estimate the true incidence of seizures with tramadol use. Alternatives such as paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) should be considered, particularly for non-severe pain conditions. Notably, the combination of tramadol and azithromycin in our case, although not known to have a direct pharmacodynamic interaction, may still contribute to increased risk through QT [ 6 ] prolongation or hepatic enzyme interaction. This warrants further research into the safety of polypharmacy in elderly patients. Our patient did not have any predisposing risk factors such as renal impairment, electrolyte disturbances, concurrent serotonergic medications, or pre-existing epilepsy. This underscores that seizure risk may be intrinsic to the pharmacological profile of tramadol and potentiated by age-related physiological changes. It is crucial to highlight that elderly patients exhibit altered pharmacodynamics, including reduced hepatic metabolism and renal clearance, leading to higher bioavailability of the drug. Several mechanisms are proposed for tramadol-induced seizures. It inhibits the reuptake of norepinephrine and serotonin, leading to an increase in excitatory neurotransmitters in the brain. It also exerts dose-dependent antagonism at gamma-aminobutyric acid-A (GABA-A) receptors, contributing to proconvulsant activity. While these effects are usually dose-related, idiosyncratic reactions have been documented even with standard doses. This case reinforces the need for heightened caution and clinical judgment when using tramadol in older populations, regardless of the absence of underlying disease. Clinicians must educate patients about the potential neurological side effects and consider safer alternatives where feasible. Conclusion Tramadol-induced seizures, though relatively uncommon, can present even in elderly patients without prior neurological disorders or other comorbidities. This case underscores the importance of recognizing tramadol as a potential cause of adverse neurological events, even in individuals who are otherwise healthy. The elderly population may be particularly susceptible due to age-related pharmacodynamic and pharmacokinetic changes, including altered drug metabolism and increased central nervous system sensitivity. This report highlights the necessity for heightened clinical vigilance when prescribing tramadol, especially in older adults. Clinicians should consider safer alternatives for pain management in this demographic and closely monitor for signs of neurotoxicity. Patient education on potential side effects and prompt reporting of any unusual symptoms are equally crucial to prevent avoidable morbidity. Rational prescribing practices, supported by individualized risk assessment, are key to minimizing iatrogenic harm in vulnerable populations. Declarations Ethics approval and consent to participate Ethical approval was not required for this case report in accordance with institutional guidelines. Written informed consent for participation and publication was obtained from the patient. Consent for publication Written informed consent was obtained from the patient for publication of this case report. Availability of data and materials All data supporting the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding The author received no external funding for the preparation or publication of this manuscript. Authors' contributions Huda Farid Akrabi conceived the case report, reviewed the literature, and prepared the manuscript. The author read and approved the final manuscript. Acknowledgements The author would like to thank the patient for consenting to share her medical information for educational purposes. Authors' information Huda Farid Akrabi is a Physician and Nephrologist at Kilimanjaro Christian Medical Centre and lecturer at Kilimanjaro Christian Medical University College, Tanzania. She completed an ISN nephrology fellowship at the University of Cape Town. References Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. Raffa RB, Friderichs E, Reimann W, et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol. J Pharmacol Exp Ther. 1992;260(1):275-85. Talaie H, Panahandeh R, Fayaznouri M, Asadi Z, Abdollahi M. Dose-independent occurrence of seizure with tramadol. J Med Toxicol. 2009;5(2):63-7. Shadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M. Tramadol overdose: a review of 114 cases. Hum Exp Toxicol. 2008;27(3):201-5. Radbruch L, Loick G, Kiencke P, et al. Topical review on the risks and benefits of tramadol. Palliat Med. 2000;14(4):299-304. Mehrpour O, Akhgari M, Davoudi M. Tramadol and seizure: a short review. J Clin Diagn Res. 2015;9(6):OE01-OE02. Gasse C, Derby L, Vasilakis-Scaramozza C, Jick H. Incidence of first-time idiopathic seizures in users of tramadol. Pharmacotherapy. 2000;20(6):629-34. Jick H, Derby LE, Vasilakis-Scaramozza C. Tramadol and seizures. Arch Intern Med. 1998;158(9):995. Rehni AK, Singh N. Tramadol-induced seizure susceptibility: possible involvement of opioid and serotonergic mechanisms. Brain Res. 2007;1185:213-20. Sen S, Goyal A, Zeczycki TN. Tramadol. [Updated 2022]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Its widespread use in both hospital and outpatient settings stems from its dual mechanism of action: weak \u0026micro;-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake. Tramadol is widely utilized in clinical settings due to its dual mechanism of action: \u0026micro;-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake. Despite being considered relatively safe, it is increasingly implicated in neurotoxicity, particularly seizures. The risk is well-documented in patients with epilepsy, renal or hepatic dysfunction, and those using interacting medications. However, seizures in healthy individuals, especially the elderly, receiving therapeutic doses are rare but clinically significant.\u003c/p\u003e\u003cp\u003eIn low-resource settings, tramadol is frequently prescribed without comprehensive patient screening, making understanding its adverse profile critical. With global aging populations, the number of elderly individuals exposed to this drug is increasing. Unfortunately, this group is often underrepresented in clinical trials. Age-associated changes in drug metabolism and blood-brain barrier permeability may predispose to adverse neurological outcomes.\u003c/p\u003e\u003cp\u003eOne of the less frequently anticipated adverse effects of tramadol is seizure activity. Although seizures are typically associated with high doses or predisposing conditions\u0026mdash;such as epilepsy, renal or hepatic impairment, or concurrent use of serotonergic drugs\u0026mdash;there is emerging evidence of seizure occurrences even in healthy individuals receiving standard doses. The mechanisms underpinning these events involve increased excitatory neurotransmitter activity and impaired inhibitory GABAergic signaling.\u003c/p\u003e\u003cp\u003eElderly patients represent a high-risk group for drug-induced neurotoxicity. Age-related changes such as decreased renal and hepatic clearance, altered blood-brain barrier permeability, and polypharmacy increase susceptibility to adverse drug reactions. Unfortunately, elderly individuals are often underrepresented in clinical trials, leading to an underappreciation of risks associated with medications like tramadol.\u003c/p\u003e\u003cp\u003eIn this report, we describe a case of tramadol-induced seizure in an elderly patient without prior comorbidities. We explore possible pathophysiological mechanisms, review existing literature on similar cases, and highlight the importance of cautious prescribing practices in this population. This case aims to alert clinicians to this hidden danger and support safer prescribing practices.\u003c/p\u003e\u003cp\u003eFinally, this report advocates for incorporating seizure risk assessments in routine prescribing practices and improving awareness among healthcare providers, especially in primary care settings. Educating patients and families about early signs of neurotoxicity and ensuring prompt medical attention can mitigate adverse outcomes.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 72-year-old female with no past medical history presented to the outpatient clinic with a 4 day history of sore throat, mild cough, and low-grade fever. She was diagnosed with an upper respiratory tract infection and prescribed azithromycin 500 mg once daily and tramadol 50 mg three times daily for symptomatic relief.\u003c/p\u003e\u003cp\u003eAfter the third dose of tramadol, the patient experienced a sudden-onset generalized tonic-clonic seizure lasting approximately one minute. She was brought to the emergency department, where she was post-ictal but hemodynamically stable.\u003c/p\u003e\u003cp\u003eClinical examination was unremarkable. Laboratory investigations including complete blood count, electrolytes, renal and liver function tests were within normal limits. A non-contrast CT scan of the brain showed no acute intracranial pathology.\u003c/p\u003e\u003cp\u003eTramadol was discontinued immediately. No antiepileptic drugs were initiated. The patient showed progressive clinical improvement and had no further seizure episodes. She was discharged in stable condition with advice to avoid tramadol and follow up with her primary care physician.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates a rare but clinically significant adverse event tramadol induced seizures in an elderly patient without any known risk factors or comorbid conditions.\u003c/p\u003e\u003cp\u003eTramadol exerts analgesic effects through \u0026micro;-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake. These mechanisms, particularly the serotonergic component, are implicated in seizure activity. While seizures have been associated with high doses, concomitant serotonergic drugs, renal/hepatic impairment, or epilepsy, our patient had none of these contributing factors. Few case reports have described similar occurrences in elderly individuals taking standard therapeutic doses without interacting medications. This suggests that age-related changes in neurophysiology or pharmacokinetics may increase susceptibility, even in seemingly low-risk patients.\u003c/p\u003e\u003cp\u003eRecent pharmacovigilance data [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] suggest tramadol-related seizures may be underreported, especially in sub-Saharan African settings where access to diagnostic tools such as EEG or MRI is limited [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This raises concern for broader undetected incidence in vulnerable populations.\u003c/p\u003e\u003cp\u003eFurthermore, a growing body of literature has demonstrated that tramadol, even when administered at therapeutic doses, may cause dose-independent seizures [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] in susceptible individuals [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Genetic polymorphisms, such as variations in CYP2D6 enzyme activity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], may contribute to this phenomenon by altering metabolism of tramadol to its active metabolite, O-desmethyltramadol [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eClinicians should also be aware of the potential interaction between tramadol and other antibiotics like azithromycin, which may increase seizure susceptibility through indirect pathways such as hepatic enzyme competition or prolonged QT [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] interval [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Although a direct causal relationship is not well-established, caution is advisable.\u003c/p\u003e\u003cp\u003eThe need for regional pharmacovigilance programs and increased education about tramadol's seizure risk is particularly important in primary care and rural settings [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Patient safety could be improved with mandatory risk disclosure during prescribing and standardized screening for elderly patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis case aligns with existing reports that caution against the liberal use of tramadol, especially among the elderly. More extensive post-marketing surveillance and pharmacovigilance are required to estimate the true incidence of seizures with tramadol use. Alternatives such as paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) should be considered, particularly for non-severe pain conditions.\u003c/p\u003e\u003cp\u003eNotably, the combination of tramadol and azithromycin in our case, although not known to have a direct pharmacodynamic interaction, may still contribute to increased risk through QT [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] prolongation or hepatic enzyme interaction. This warrants further research into the safety of polypharmacy in elderly patients.\u003c/p\u003e\u003cp\u003eOur patient did not have any predisposing risk factors such as renal impairment, electrolyte disturbances, concurrent serotonergic medications, or pre-existing epilepsy. This underscores that seizure risk may be intrinsic to the pharmacological profile of tramadol and potentiated by age-related physiological changes. It is crucial to highlight that elderly patients exhibit altered pharmacodynamics, including reduced hepatic metabolism and renal clearance, leading to higher bioavailability of the drug.\u003c/p\u003e\u003cp\u003eSeveral mechanisms are proposed for tramadol-induced seizures. It inhibits the reuptake of norepinephrine and serotonin, leading to an increase in excitatory neurotransmitters in the brain. It also exerts dose-dependent antagonism at gamma-aminobutyric acid-A (GABA-A) receptors, contributing to proconvulsant activity. While these effects are usually dose-related, idiosyncratic reactions have been documented even with standard doses.\u003c/p\u003e\u003cp\u003eThis case reinforces the need for heightened caution and clinical judgment when using tramadol in older populations, regardless of the absence of underlying disease. Clinicians must educate patients about the potential neurological side effects and consider safer alternatives where feasible.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTramadol-induced seizures, though relatively uncommon, can present even in elderly patients without prior neurological disorders or other comorbidities. This case underscores the importance of recognizing tramadol as a potential cause of adverse neurological events, even in individuals who are otherwise healthy. The elderly population may be particularly susceptible due to age-related pharmacodynamic and pharmacokinetic changes, including altered drug metabolism and increased central nervous system sensitivity. This report highlights the necessity for heightened clinical vigilance when prescribing tramadol, especially in older adults. Clinicians should consider safer alternatives for pain management in this demographic and closely monitor for signs of neurotoxicity. Patient education on potential side effects and prompt reporting of any unusual symptoms are equally crucial to prevent avoidable morbidity. Rational prescribing practices, supported by individualized risk assessment, are key to minimizing iatrogenic harm in vulnerable populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Ethical approval was not required for this case report in accordance with institutional guidelines. Written informed consent for participation and publication was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Written informed consent was obtained from the patient for publication of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;All data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The author received no external funding for the preparation or publication of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Huda Farid Akrabi conceived the case report, reviewed the literature, and prepared the manuscript. The author read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The author would like to thank the patient for consenting to share her medical information for educational purposes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information\u0026nbsp;\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Huda Farid Akrabi is a Physician and Nephrologist at Kilimanjaro Christian Medical Centre and lecturer at Kilimanjaro Christian Medical University College, Tanzania. She completed an ISN nephrology fellowship at the University of Cape Town.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGrond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923.\u003c/li\u003e\n\u003cli\u003eRaffa RB, Friderichs E, Reimann W, et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol. J Pharmacol Exp Ther. 1992;260(1):275-85.\u003c/li\u003e\n\u003cli\u003eTalaie H, Panahandeh R, Fayaznouri M, Asadi Z, Abdollahi M. Dose-independent occurrence of seizure with tramadol. J Med Toxicol. 2009;5(2):63-7.\u003c/li\u003e\n\u003cli\u003eShadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M. Tramadol overdose: a review of 114 cases. Hum Exp Toxicol. 2008;27(3):201-5.\u003c/li\u003e\n\u003cli\u003eRadbruch L, Loick G, Kiencke P, et al. Topical review on the risks and benefits of tramadol. Palliat Med. 2000;14(4):299-304.\u003c/li\u003e\n\u003cli\u003eMehrpour O, Akhgari M, Davoudi M. Tramadol and seizure: a short review. J Clin Diagn Res. 2015;9(6):OE01-OE02.\u003c/li\u003e\n\u003cli\u003eGasse C, Derby L, Vasilakis-Scaramozza C, Jick H. Incidence of first-time idiopathic seizures in users of tramadol. Pharmacotherapy. 2000;20(6):629-34.\u003c/li\u003e\n\u003cli\u003eJick H, Derby LE, Vasilakis-Scaramozza C. Tramadol and seizures. Arch Intern Med. 1998;158(9):995.\u003c/li\u003e\n\u003cli\u003eRehni AK, Singh N. Tramadol-induced seizure susceptibility: possible involvement of opioid and serotonergic mechanisms. Brain Res. 2007;1185:213-20.\u003c/li\u003e\n\u003cli\u003eSen S, Goyal A, Zeczycki TN. Tramadol. [Updated 2022]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Kilimanjaro Christian Medical Centre","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tramadol, Seizures, Elderly, Azithromycin, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-7837568/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7837568/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTramadol is a widely used analgesic for moderate to severe pain due to its dual mechanism of \u0026micro;-opioid receptor agonism and monoaminergic reuptake inhibition. While generally perceived as safe, it has been increasingly associated with neurotoxic side effects, particularly seizures. These adverse effects are commonly reported in patients with epilepsy, polypharmacy, or organ dysfunction. However, seizure events in elderly individuals without known risk factors are rare and underreported.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e\u003cp\u003eWe describe a 72-year-old woman with no prior medical history who developed a generalized tonic-clonic seizure after administration of tramadol for an upper respiratory tract infection. She had received three therapeutic doses of tramadol. Her laboratory investigations and neuroimaging were unremarkable. Following withdrawal of the drug, the patient made a full recovery with no further seizure activity.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e\u003cp\u003eElderly patients are particularly vulnerable to adverse drug reactions due to altered pharmacokinetics and pharmacodynamics associated with aging. This case highlights the potential for tramadol to induce seizures even in the absence of predisposing comorbidities or drug interactions. Clinicians should be vigilant when prescribing tramadol to older individuals and should consider alternatives for pain control.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eTramadol should be prescribed with caution in elderly populations, regardless of apparent baseline health. Clinician awareness of tramadol\u0026rsquo;s seizure risk even at therapeutic doses is essential to patient safety.\u003c/p\u003e","manuscriptTitle":"Tramadol-Induced Seizures in an Elderly Patient Without Comorbidities: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-14 05:46:08","doi":"10.21203/rs.3.rs-7837568/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5f8605a7-8fc5-4372-9816-0fe0a5ac92a7","owner":[],"postedDate":"October 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56144102,"name":"Neurology"},{"id":56144103,"name":"Clinical Pharmacology"},{"id":56144104,"name":"Geriatrics \u0026 Gerontology"}],"tags":[],"updatedAt":"2025-10-14T05:46:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-14 05:46:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7837568","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7837568","identity":"rs-7837568","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}