Stronger and higher dose opioids linked to greater all-cause mortality risk

A new international study spanning the United Kingdom, United States, and Canada has revealed important insights into the risks associated with prescribed opioid use for noncancer pain. 

The research, led by researchers at The University of Manchester and McGill University in Canada which analysed over 1 million patients newly initiated on opioids, found prescription of strong opioids was associated with higher risk of all-cause mortality compared to taking codeine.

 Strong opioids include morphine, fentanyl, and oxycodone, as well as combination opioids. 

Funded by the Canadian Institutes of Health Research the UK National Institute for Health and Care Research, the study findings, published today in  the journal Pain(insert date and link to paper) is one of the first to provide clarity on the comparative safety of different types of opioids across different countries. 

Additionally, patients taking 50 or more morphine milligram equivalents per day experienced an incremental higher risk of death. 

Morphine milligram equivalents are a way to compare the strength of different opioid medications to morphine which enables measurement of how much opioid a person is taking, no matter which specific drug is prescribed.

 The researchers also found that:

• UK patients on morphine had more than 12 times the risk of all-cause mortality compared to codeine users after adjusting for confounding factors. Similarly elevated risks were observed in the US and Canada after such adjustments. Elevated risks were also seen with fentanyl, oxycodone and buprenorphine.
• A history of depression and prior substance abuse were associated with an increased risk of death across all cohorts and in most subgroups.
• In the UK, the use of antipsychotics and benzodiazepine medications at the same time as an opioid was associated with higher risk of death across all three subgroups.
• Being on more than one type of opioid was associated with a significantly higher risk of mortality.. 

Dr Meghna Jani, NIHR Advanced Fellow and Senior Clinical Lecturer at the Centre for Epidemiology Versus Arthritis, The University of Manchester was the lead author of the study. 

She is also based at the North Care Alliance NHS Foundation Trust  and a researcher within the NIHR Manchester Biomedical Research Centre. 

She said: “It is understandable that some people do need to be prescribed opioids for pain especially in the short term given the limited options for pain relief. 

“What these study findings allow is for people to make more informed choices about the types of pain relief or specific opioid to get started on based on scientific evidence across multiple countries.” 

She added: “The morphine milligram equivalent thresholds at which the risks of opioid use are considered to outweigh the benefits, vary considerably across current international guidelines. 

“This study highlights the importance of closely monitoring patients on or approaching doses of 50 or more morphine milligram equivalents per day. 

“It also suggests having earlier, open discussions with patients on such doses to explore alternative treatments and provide additional support, especially for those with risk factors for serious opioid-related harms. 

“However instead of stopping the use of stronger opioids outright, shared decisions need to be made collaboratively between patients and healthcare professionals, considering each person’s unique situation”.

An embargoed copy of the paper Comparative risk of mortality in new users of prescription opioids for non-cancer pain: results from the International Pharmacosurveillance Study , published in Pain  – the journal from the International Association for the Study of Pain -is available here