A major study has ranked opioid painkillers by how dangerous they may be, highlighting which drugs appear to carry the greatest risk of a fatal overdose and which are linked to comparatively lower dangers.
Researchers at the University of Manchester examined how different opioid medications affect patients and found that some were much more strongly associated with respiratory depression, a serious complication that can lead to overdose deaths.
The study, published in BMC Medicine, looked at electronic health records for 32,909 adult inpatients in north-west England who were being treated for non-cancer pain. Researchers compared the risk of breathing problems across different opioids and also examined whether combinations of opioids, or use alongside other sedating medicines, changed the risk.
The findings are especially notable given the scale of opioid misuse in the US. Recent federal survey data estimate that 4.8 million Americans had opioid use disorder in 2024.
The study focused on opioids and their effects on breathing, as respiratory depression is one of the main pathways through which overdoses become deadly.
According to the Cleveland Clinic, respiratory depression (hypoventilation) is a condition which is “when you breathe too slowly or too shallowly, leading to carbon dioxide building up in your blood”.
If that happens, it can progress into respiratory failure or even cardiac arrest.
Opioid overdoses can also be reversed if they are recognized quickly enough. Health agencies say naloxone can help restore breathing in an emergency, but immediate medical attention is still essential.
The research arrives as the US continues to struggle with widespread opioid addiction. A 2024 federal survey estimated that 4.8 million Americans aged 12 or older had opioid use disorder in the past year.
These medications are powerful painkillers commonly prescribed after surgery, following major injuries, or during cancer treatment. The opioid category includes morphine, codeine, tramadol and fentanyl.
Among those drugs, fentanyl was linked to the highest potential danger in the study.
The team reviewed electronic health records covering 32,909 adults in north-west England who were receiving treatment.
They specifically looked for signs that patients’ breathing had fallen to dangerously low levels after taking opioid medication.
The results showed that patients receiving fentanyl were three times more likely to experience breathing problems and 85 per cent more likely to develop respiratory depression than patients prescribed morphine.
In the study, oxycodone and morphine were also linked to a higher risk of breathing problems than codeine, while combination opioid treatments carried a greater risk than taking morphine alone. By contrast, topical buprenorphine was not linked to a statistically significant increase in respiratory depression risk.
Opioids are widely used in pain treatment and pain management, and fentanyl “is a potent synthetic opioid drug approved by the Food and Drug Administration” for that purpose.
But the Drug Enforcement Administration says it is “approximately 100 times more potent than morphine and 50 times more potent than heroin as an analgesic”.
According to the National Institute on Drug Abuse, fentanyl can make users feel happy and relaxed, but it can also increase the urge to take more.
The institute also says fentanyl’s side effects can vary from mild to severe, with reported issues including “confusion, drowsiness, nausea, visual disturbances, constipation, muscle stiffness, and many others.”
It explained that “like other opioids, fentanyl affects the parts of the brain that control breathing”, and when a “person takes a higher fentanyl dose than their body can handle (an overdose), their breathing can slow to a life-threatening level.”
The study also found that the danger is not limited to fentanyl alone, because combining opioids can further increase the risk.
Both oxycodone and morphine were associated with a greater chance of breathing problems than codeine, while people taking more than one opioid had a 50 per cent higher risk than those taking only morphine.
Dr Meghna Jani, a senior clinical lecturer at the University of Manchester and senior author of the study, said:
“Opioids remain important medicines for managing severe acute pain. Our findings show that the risks are not the same across all opioid drugs or doses.”
“A key strength of our study was our ability to use detailed hospital electronic health records to accurately capture when opioids were actually administered to patients, alongside routinely collected vital signs to identify changes in breathing.
Dr Jani added:
“Understanding how different medicines and combinations affect respiratory safety can help clinicians and patients make more informed prescribing decisions together, as well increasing awareness of what dose thresholds require closer monitoring.”
The broader medical advice remains clear: opioids should be used only as prescribed, and patients at higher risk of overdose may need closer monitoring, especially when taking other medicines that can also slow breathing, such as benzodiazepines or gabapentinoids.