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Is tramadol associated with an increase in all-cause mortality among patients with osteoarthritis?
  1. Catrin Page,
  2. Teck K Khong
  1. Clinical Pharmacology, St George's, University of London, London, UK
  1. Correspondence to Dr Teck K Khong, Clinical Pharmacology, St George's University of London, London, UK; tkhong{at}

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Commentary on: Zeng C, Dubreuil M, LaRochelle MR, et al. Association of tramadol with all-cause mortality among patients with osteoarthritis. JAMA 2019;321:969–82

Commentary by: Dr Catrin Page and Dr Teck Khong Clinical Pharmacology, St George's, University of London, UK

Series Editor: Dr Teck Khong, DTB Associate Editor Clinical Pharmacology, St George's, University of London, London, UK

Key learning points

  • Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line options for the pharmacological management of chronic pain associated with osteoarthritis.

  • Tramadol is a weak short-acting opioid that was originally claimed to cause less constipation and respiratory depression than conventional opioids and that it offered a special ‘dual action’.

  • This retrospective cohort study suggests that tramadol may be associated with a higher risk of mortality compared with commonly prescribed NSAIDs (naproxen, diclofenac, celecoxib, etoricoxib) but not when compared with codeine.


A cohort study of patients with osteoarthritis found that an initial prescription of tramadol was associated with a higher risk of mortality over 1 year of follow-up compared with commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) but not when compared with codeine.1 Although potential confounding cannot be excluded, tramadol should be used with the same caution as other opioids.

Study details

This retrospective cohort study examined all-cause mortality within 1 year of an initial tramadol prescription compared with five other commonly used analgesics among patients with osteoarthritis.1 Data were taken from the UK Health Improvement Network (THIN) electronic medical record database derived from the records of 580 general practices (11 million patients). The authors identified patients aged ≥50 years with hand, hip or knee osteoarthritis who were taking tramadol or one of five other pain relief medicines (codeine, celecoxib, diclofenac, etoricoxib or naproxen). All patients had visited their GP surgery between January 2000 and December 2015 …

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  • Competing interests None declared. Refer to the online supplementary files to view the ICMJE form(s).

  • Provenance and peer review Commissioned; internally peer reviewed.