Tramadol may be associated with increased mortality among patients with osteoarthritis

1. In this retrospective cohort of patients with osteoarthritis, tramadol had a significantly higher risk of mortality over 1 year compared to NSAIDs, though there were many confounding factors precluding determination of a causal relationship.

2. No differences in mortality were found when comparing tramadol and codeine.

Evidence Rating Level: 2 (Good)           

Study Rundown: Tramadol is a weak opioid agonist that is commonly recommended for and prescribed to patients with osteoarthritis. Previous studies have shown that it provides similar pain relief when compared to nonsteroidal anti-inflammatory drugs (NSAIDs), but may be associated with more opioid-related adverse events, such as nausea, dizziness, constipation, and vomiting. In this retrospective cohort study, osteoarthritis patients prescribed tramadol had higher mortality rates at 1 year compared with those who received naproxen, diclofenac, celecoxib, and eterocoxib. No difference in mortality was found when comparing tramadol and codeine.

Overall, this study suggests that tramadol prescriptions in patients with osteoarthritis may be more dangerous compared to commonly prescribed NSAIDs. There are several study limitations, most notably confounding by indication, as patients prescribed tramadol were older, had higher BMI, had osteoarthritis for a longer duration, a higher prevalence of comorbidities, and larger prescription burden compared with patients taking NSAIDs, though groups were balanced by propensity score matching before analysis.

Click to read the study in JAMA

Relevant Reading: Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review

In-Depth [retrospective cohort]: In this sequential, propensity score-matched cohort study that was conducted in the United Kingdom, 88,902 patients were analyzed through The Health Improvement Network (THIN) database, which contains electronic medical records from general practitioners (GP). Inclusion criteria included patients aged 50 years or older with history of knee, hip, or hand osteoarthritis who visited a GP between January 2000 and December 2015 and had at least 1 year of continuous enrollment with the practice. Exclusion criteria included those with a history of cancer or an opioid use disorder prior to study entry. The study utilized 5 sequential propensity score-matched cohort studies to compare all-cause mortality between participants that received an initial prescription of tramadol to those that received an initial prescription of naproxen, diclofenac, celecoxib, eterocoxib, or codeine. Primary outcomes included all-cause mortality at 1 year after initial prescription of tramadol and 5 other pain relief medications. Initial prescription of tramadol was associated with a significantly higher risk of mortality at 1 year when compared with naproxen (hazard ratio, 1.71; CI95 1.41 to 2.07), diclofenac (HR 1.88; CI95 1.51 to 2.35), celecoxib (HR 1.70; CI95 1.33 to 2.17), and eterocoxib (HR 2.04; CI95 1.37 to 3.03), but not codeine (HR 0.94; CI95 0.83 to 1.05). Patients who received tramadol were older, had higher BMI, longer osteoarthritis duration, a higher prevalence of comorbidities (such as peptic ulcer, chronic kidney disease, diabetes, hypertension, and cardiovascular diseases), other prescriptions, and health care utilization than patients who received NSAIDs before propensity score matching.

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