Document Type : Case Report


Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: Tramadol is a synthetic analgesic with two mechanisms. The opioid and non-opioid mechanisms are responsible for tramadol side effects. Non-opioid side effects of tramadol are due to the reuptake inhibitions of serotonin and norepinephrine. Some of the side effects include anaphylactoid reactions, CNS depression, hypoglycemia, hypotension, respiratory depression, seizures, and serotonin syndrome. Seizure may happen in therapeutic doses. If the frequency of tramadol seizures increases, ischemic brain injury and hypoxic-ischemic encephalopathy can be induced.
Case Report: We report a young man with a history of tramadol abuse that was admitted with status epilepticus in Imam Reza hospital in Mashhad, Iran. Due to his altered mental status, he was intubated and antiepileptic agents were prescribed. He was transferred to ICU. After regaining consciousness, he was extubated and with the prescription of rehabilitation support he was discharged.
Conclusion: Tramadol is a synthetic analgesic agent with less potential for dependence. It is important to mention that the overdose of this drug is common. This drug has two mechanisms. This paper reports a case that developed generalized tonic clonic seizures due to tramadol and hypoxic ischemic encephalopathy. With adequate treatment and supportive care, patient’s mental status improves and he/she can be discharged.


Main Subjects

1. American Pain Society (APS). Principles of Analgesic Use. 7th ed. Chicago, IL: APS; 2016.
2. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet 2004; 43(13): 879-923. doi: 10.2165/00003088-200443130-00004.
3. Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, et al. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother 2012; 13(10): 1437-49. doi:
4. Fournier JP, Azoulay L, Yin H, Montastruc JL, Suissa S. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain.JAMA Intern Med 2015; 175(2): 186-93. doi: 10.1001/jamainternmed.2014.6512.
5. Shipton EA. Tramadol--present and future. Anaesth Intensive Care 2000; 28(4): 363-74. doi: 10.1177/0310057x0002800403.
6. 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. doi:10.1592/phco.20.7.629.35174.
7. Rehni AK, Singh I, Kumar M. Tramadol-induced seizurogenic effect: a possible role of opioid-dependent gamma-aminobutyric acid inhibitory pathway. Basic Clin Pharmacol Toxicol 2008; 103(3): 262-6. doi: 10.1111/j.1742- 7843.2008.00276.x.
8. Sun C, Mtchedlishvili Z, Erisir A, Kapur J. Diminished neurosteroid sensitivity of synaptic inhibition and altered
location of the alpha4 subunit of GABA(A) receptors in an animal model of epilepsy. J Neurosci 2007; 27(46): 12641- 50. doi: 10.1523/jneurosci.4141-07.2007.
9. Wightman RS, Perrone J, Erowid F, Erowid E, Meisel ZF, Nelson LS. Comparative analysis of opioid queries on erowid. org: an opportunity to advance harm reduction. Subst Use Misuse 2017; 52(10): 1315-9. doi: 10.1080/10826084.2016.1276600.
10. Shadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M. Tramadol intoxication: a review of 114 cases. Hum ExpToxicol 2008; 27(3): 201-5. doi: 10.1177/0960327108090270.
11. Afshari R, Tashakori A. Tramadol overdose as a cause of serotonin syndrome: a case series. Clin Toxicol 2010; 48(4):
337-41. doi: 10.3109/15563651003709427.
12. Talaie H, Panahandeh R, Fayaznouri MR, Asadi Z, Abdollahi M. Dose-independent occurrence of seizure with tramadol.
J Med Toxicol 2009; 5(2): 63-7. doi: 10.1007/BF03161089.
13. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic
reviews. Gen Hosp Psychiatry 2009; 31(3): 206-19. doi:10.1016/j.genhosppsych.2008.12.006.
14. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S, Quality Standards Subcommittee of the American Academy
of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 67(2): 203-10. doi: 10.1212/
15. Boora K. Tramadol. In: Enna SJ, Bylund DB, eds. xPharm: The Comprehensive Pharmacology Reference. New York:
Elsevier; 2007. p. 1-7. doi: 10.1016/B978-008055232-3.62788-6
16. Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank’s Toxicologic Emergencies. 10th ed. US: McGraw-Hill; 2015.
17. Musshoff F, Madea B. Fatality due to ingestion of tramadol alone. Forensic Sci Int 2001; 116(2-3): 197-9. doi: 10.1016/s0379-0738(00)00374-1.
18. Cock HR. Drug-induced status epilepticus. Epilepsy Behav 2015; 49: 76-82. doi: 10.1016/j.yebeh.2015.04.034.
19. Vignatelli L, Tonon C, D’Alessandro R, Bologna Group for the Study of Status Epilepticus. Incidence and shortterm
prognosis of status epilepticus in adults in Bologna, Italy. Epilepsia 2003; 44(7): 964-8. doi: 10.1046/j.1528-
20. Márquez-Romero JM, Zermeño-Pohls F, Soto-Cabrera E. Convulsive status epilepticus associated with a tramadol
overdose. Neurologia 2010; 25(9): 583-5. doi: 10.1016/j.nrl.2009.07.001. [In Spanish].
21. Mehrpour M. Intravenous tramadol-induced seizure:two case reports. Iranian Journal of Pharmacology and
Therapeutics 2005; 4(2): 146-7.
22. Boostani R, Derakhshan S. Tramadol induced seizure: A 3-year study. Caspian J Intern Med 2012; 3(3): 484-7.
23. Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart RC. Factors related to seizure in
tramadol poisoning and its blood concentration. J Med Toxicol 2011; 7(3): 183-8. doi: 10.1007/s13181-011-0168-0.