Mortality Risk Rises for Osteoarthritis Patients on Tramadol

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Osteoarthritis patients over age 50 could face a greater risk of mortality after receiving an initial tramadol prescription compared to various commonly prescribed NSAIDS, according to new research.

The study, published in the March Journal of the American Medical Association issue, examined tramadol all-cause mortality because prescriptions for the weak opioid doubled between 2003 and 2009 and remained high as of 2015.

“This study found that initial prescription of tramadol was associated with a significantly increased mortality rate over the next year compared with commonly prescribed NSAIDs among participating with osteoarthritis,” said lead author Yuqing Zhang, M.D., a Massachusetts General Hospital epidemiologist.

To determine the level of risk patients with knee, hip, or hand osteoarthritis face, researchers examined electronic health records from January 2000 to December 2015 on 88,902 patients included in The Health Improvement Network in the United Kingdom. Half received tramadol; other patients received naproxen (12,397), diclofenac (6,512), celecoxib (5,674), etoricoxib (2,946), or codeine (16,922).

According to results, at a one-year follow-up in December 2016, investigators said, patients who received tramadol had a higher morality risk than those taking all other NSAIDs except codeine. Findings revealed there was no statistically significant difference in mortality between tramadol and codeine.

The exact link between tramadol and mortality is unclear, researchers said, but the medication may activate opioid receptors and inhibit central serotonin and norepinephrine re-uptake, leading to negative neurological impacts, including serotonin syndrome and seizures. Tramadol may also increase the risk of postoperative delirium which can also raise mortality risk.

These findings could also have clinical impacts, investigators said. If a true cause-and-effect link between tramadol and mortality is unearthed, it could lead to tramadol receiving an unfavorable safety profile. 

These results have also led to several strategies that could, potentially, reduce the negative effects associated with analgesic use. For example, co-prescription of proton pump inhibitors with oral NSAIDs has been a considered a cost-effective approach to treating osteoarthritis patients with a moderate-to-high gastrointestinal risk.

Ultimately, investigators said, additional research is needed to determine whether the tramadol-mortality association is causal.

REFERENCE

Zeng C, Dubreuil M, LaRochelle M, Lu N, Wei J, Choi H, Lei G, Zhang Y, Association of Tramadol With All-Cause Mortality Among Patients With Osteoarthritis. Journal American Medical Association (2019), doi: 10.1001/jama.2019.1347.