Tramadol intake is associated with a higher risk of mortality compared to codeine, according to study results published in JAMA.
Tramadol is considered a relatively safe opioid and is widely used to treat patients with chronic non-cancerous pain. With limited data on the safety of tramadol compared to other opioids, the aim of the current study was to compare tramadol with codeine and to determine the risk of mortality and other adverse clinical outcomes in the outpatient setting.
The retrospective, population-based cohort study with propensity score matching used a primary care database of medical records and pharmacy deliveries for more than 80% of the population of Catalonia, Spain. The study sample comprised patients ≥ 18 years of age who were prescribed tramadol or codeine between 2007 and 2017 and were followed up until December 31, 2017.
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The results studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse / addiction, and sleep disorders within one year of first administration.
After study exclusions and propensity score matching, the final analysis comprised 368,960 patients (mean age 53.1 years; 57.3% women), of whom 184,480 were in the tramadol cohort and 184,480 in the codeine cohort. The most common diagnoses were back pain (47.5% and 48.5%), neck / shoulder pain (28.6% and 29.5%) and osteoarthritis (15.3% and 15.5%).
Compared to codeine, the use of tramadol was significantly associated with an increased risk of mortality (13.00 vs. 5.61 per 1000 person-years; hazard ratio) [HR], 2.31; 95% CI 2.08–2.56), cardiovascular events (10.03 vs. 8.67 per 1000 person-years; HR 1.15; 95% CI 1.05–1.27) and fractures (12, 26 vs. 8.13 per 1000 person-years; HR, 1.50; 95% CI, 1.37-1.65).
According to subgroup and sensitivity analyzes, the increased mortality risk associated with tramadol was higher in young (HR 3.14; 95% CI 1.82-5.41) than in older adults (HR 2.39; 95% CI 2.20) -2.60). In addition, the risk of cardiovascular events was significantly higher in women (HR 1.32; 95% CI 1.19-1.46) than in men (HR 1.03; 95% CI 0.93-1 , 13).
There were no significant differences between the medications with regard to the risk of falls, delirium, constipation, opioid abuse / dependence, or sleep disorders.
The study had several limitations, including potential mix-ups by indication, unmeasured mix-ups, lack of data on cause of death, and potential underestimation of some study results in routine clinical practice, such as delirium and insomnia.
“In this population-based cohort study, a new prescription dispensing of tramadol was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures compared to codeine, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse / dependence or sleep disorders, ”the researchers concluded.
Disclosure: Some study authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of author disclosures, see the original reference.
reference
Xie J, Strauss VY, Martinez-Laguna D, et al. Association of tramadol vs. codeine prescription with mortality and other adverse clinical outcomes. JAMA. October 19, 2021. doi: 10.1001 / jama.2021.15255
