Troublesome tramadol

3 minute read

A study of osteoarthritis adds to the growing evidence of the risk of hip fractures and mortality associated with tramadol.

A study of osteoarthritis patients in Canada adds to the growing evidence of the risk of hip fractures and mortality associated with tramadol.

Pain relief is a primary concern for osteoarthritis patients since no effective treatments are available to halt disease progression.

Tramadol is a so-called weak opioid, introduced in Australia in late 1998. It is no longer recommended by Australian peak medical bodies after reports of adverse effects increased steadily year on year and a 2019 Cochrane review underscored that position.

According to estimates published in late 2016, around 5% of OA patients in Australia are on tramadol, with a similar proportion of users among osteoarthritis patients in British Columbia as of 2014.

However, tramadol is associated with a higher rate of mortality and risk of hip fractures than other pain relief medications commonly prescribed for osteoarthritis, such as NSAIDs.

And yet since 2012, the American College of Rheumatologists has conditionally recommended tramadol as first-line therapy for patients with knee osteoarthritis, along with NSAIDs.

Researchers from the Arthritis Research Canada have now examined the risk of cardiovascular disease  and venous thromboembolism, as well as all-cause mortality and hip fractures, associated with tramadol prescription among osteoarthritis patients in British Columbia between 2005 to 2014.

Lingyi Li, the lead author and a PhD candidate from the University of British Columbia, presented the findings at EULAR.

The study[1] – which compared tramadol with three NSAIDs (naproxen, diclofenac and Cox-2 inhibitors) and codeine in over 112,000 Canadian OA patients – reaffirmed previous findings from UK cohorts published earlier this year.[2],[3]

Tramadol was associated with an increased risk of all-cause mortality and hip fractures one year after the first prescription, compared with all three NSAIDs, but not codeine.

A higher one-year risk of cardiovascular disease and venous thromboembolism among tramadol users was also reported compared with patients prescribed diclofenac and Cox-2 inhibitors only.

Professor David Hunter, a rheumatologist from the Institute of Bone and Joint Research in Sydney, said the inclusion of CVD and VTE in this analysis was novel and may provide some mechanistic insights into the cause of the increased mortality associated with tramadol – although there is always potential for confounding effects with observational studies.

Professor Hunter noted that the reported increase in absolute risk for all-cause mortality, venous thromboembolism and cardiovascular disease was only small, however, he said the result is important considering how frequently this medication is used worldwide.

“Even a small increase in absolute risk leads to a relatively large number of adverse cases, as were seen in this relatively large sample size,” he said.

Professor Hunter also stressed that the risk for venous thromboembolism, hip fractures and concomitant cardiovascular disease is already higher in people with OA – before adding tramadol into the mix.

“With the real risks of morbidity and mortality in an at-risk population of OA patients, there is little justification for its use,” he said. 


[1] Ann Rheum Dis 2020, 2 June

[2] JAMA 2019, 12 March

[3] JBMR 2020, 5 February

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