Tramadol use linked to higher risk of mortality, compared to codeine: JAMA

Published On 2021-10-23 05:15 GMT   |   Update On 2021-10-23 06:50 GMT

Spain: In a study conducted by Junqing Xie and team, it was found that a new tramadol prescription was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures when compared to codeine. However  there was no significant difference in the other side effects risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders.


The findings of this study were published in the Journal of American Medical Association (JAMA) on 19th October 2021.

Although tramadol is increasingly being used to treat chronic non cancer pain, few safety studies have been conducted to compare it to other opioids. The objective of this study was to compare the effects of tramadol and codeine on mortality and other unfavorable clinical outcomes in outpatient settings.


This was a retrospective, population-based, propensity score-matched cohort research that used a primary care database with routinely collected medical records and pharmaceutical dispensations to cover more than 80% of Catalonia's (6 million people) population. Patients 18 years of age or older with 1 year or more of available data and tramadol or codeine dispensation (2007-2017) were enrolled and followed up to December 31, 2017.


A new prescription dispensation of tramadol, compared to codeine, was significantly associated with a higher risk of all-cause mortality (HR, 2.31), cardiovascular events (HR, 1.15), and fractures (HR, 1.50), but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders in this retrospective cohort study that used propensity score matching and included 368 960 participants.


In conclusion, when compared to codeine, new tramadol prescriptions were substantially linked with a greater risk of death, cardiovascular events, and fractures, however, the data should be taken with caution because of the possibility of residual confounding.


Xie J, Strauss VY, Martinez-Laguna D, et al. Association of Tramadol vs Codeine Prescription Dispensation With Mortality and Other Adverse Clinical Outcomes. JAMA. 2021;326(15):1504–1515. doi:10.1001/jama.2021.15255

Article Source : Journal of American Medical Association

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