text: The clinical presentation in overdose cases can vary but typically includes neurological, cardiovascular, and gastrointestinal manifestations. The predominant neurological symptoms are seizures and altered levels of consciousness, ranging from somnolence to coma. Seizures are particularly notable due to tramadol's lowering of the seizure threshold, occurring in approximately half of acute poisoning cases. Patients often exhibit tachycardia and mild hypertension. Gastrointestinal disturbances such as nausea and vomiting are common, and agitation, anxiety, and cold and clammy skin may also be present.
  While less common, severe complications like respiratory depression and serotonin syndrome can occur, particularly in polydrug overdoses involving other CNS depressants (such as benzodiazepines, opioids, and alcohol) and agents with serotonergic activity. Additionally, Individuals with genetic variations leading to CYP2D6 enzyme duplication (rapid metabolizers) may have an increased risk of adverse effects, due to faster conversion of tramadol to its active metabolite.
  Acute tramadol overdose is generally not life-threatening, with most fatalities resulting from polysubstance overdose. Management includes cardiovascular monitoring, activated charcoal administration, hydration, and treatment of seizures. Naloxone, an opioid antagonist, can partially reverse some effects of tramadol overdose, particularly respiratory depression. However, its use may increase the risk of seizures due to unopposed alpha-adrenergic stimulation. For suspected serotonin syndrome, cyproheptadine, a serotonin antagonist, is considered an effective antidote.
  The incidence of tramadol-related overdose deaths has been on the rise in certain regions. For instance, Northern Ireland has reported an increased frequency of such cases. In 2013, England and Wales recorded 254 tramadol-related deaths, while Florida reported 379 cases in 2011. In 2011, 21,649 emergency room visits in the United States were related to tramadol. The likely explanation for these observations is due to increase in frequency of prescriptions and use due to easier access due to lighter regulatory scheduling by authorities but this is starting to change. In 2021, Health Canada announced tramadol would be added to Schedule I of the Controlled Drugs and Substances Act and to the Narcotic Control Regulations due to tramadol being suspected of having contributed to 18 reported deaths in Canada between 2006 and 2017.