Skip to main content

Tramadol Use Linked to Higher Risk of Early Death in Osteoarthritis

March 12, 2019

By Megan Brooks

NEW YORK (Reuters Health) -Tramadol may be associated with a higher risk of dying early than other pain-relief medications among patients with osteoarthritis, a large observational study from the U.K. suggests.

"These findings, if confirmed by future studies, raise a concern of safety profile of tramadol for the management of osteoarthritis," authors Drs. Chao Zeng and Yuqing Zhang of Harvard Medical School in Boston and Dr. Guanghua Lei of China's Central South University in Changsha said in a joint email to Reuters Health.

"Tramadol may be not as safe as some clinicians have perceived, and non-opioid therapies, such as exercise, physical therapy, topical nonsteroidal anti-inflammatory drugs, could be preferred for management of osteoarthritis," they said.

Using a U.K. database of general-practice electronic medical records, the researchers examined the association of initial prescription of tramadol with all-cause mortality (versus other medications) in a propensity-matched cohort of more than 88,000 people aged 50 and older (mean age 70) with osteoarthritis.

A total 44,451 were initially prescribed tramadol, 12,397 naproxen, 6,512 diclofenac, 5,674 celecoxib, 2,946 etoricoxib and 16,922 codeine.

According to a report in JAMA today, initial prescription of tramadol was associated with a significantly increased risk of dying over one year compared with initial prescription of naproxen (hazard ratio, 1.71), diclofenac (HR, 1.88), celecoxib (HR, 1.70), and etoricoxib (HR, 2.04), but not compared with codeine (HR, 0.94).

The researchers caution that the findings may be susceptible to confounding by indication considering that those given tramadol initially had higher comorbidity burden than those given NSAIDs initially (before propensity-score matching). They say further study is needed to determine if this association is causal.

They note in their paper that tramadol is a "weak opioid agonist and has been considered a potential alternative to NSAIDs and traditional opioids because of its assumed relatively lower risk of serious cardiovascular and gastrointestinal adverse effects than NSAIDs, as well as a lower risk of addiction and respiratory depression compared with other opioids." Use of tramadol has been increasing since 2000.

"Tramadol is one of the most commonly prescribed pain relief medications for the management of osteoarthritis, and several professional organizations have strongly or conditionally recommended tramadol as first-line therapy for patients with osteoarthritis," Drs. Zeng, Zhang and Lei told Reuters Health. "Both clinicians and patients should be cautious on the potential risk of tramadol on all-cause mortality. Our findings, if confirmed by further research, call for revisit of osteoarthritis treatment guidelines."

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Natural Science Foundation of China. The authors have declared no relevant conflicts of interest.


JAMA 2019.

(c) Copyright Thomson Reuters 2019. Click For Restrictions -

Back to Top