A recent comprehensive study has identified specific opioid painkillers that carry the highest risk of fatal overdose, with fentanyl showing the strongest association with respiratory depression, the primary cause of death from these drug overdoses. Respiratory depression occurs when breathing becomes dangerously slow or shallow, leading to oxygen deprivation and a buildup of carbon dioxide in the blood.
Researchers from the University of Manchester analyzed electronic health records from over 32,000 adult patients in northwest England, focusing on those prescribed opioids for non-cancer pain. The study, published in BMC Medicine, aimed to determine which opioids were most closely linked to life-threatening respiratory issues. Using medical tests to detect signs of dangerously slowed breathing, such as low oxygen levels and the need for naloxone (an overdose reversal medication), the team tracked opioid administration and its effects.
When compared to codeine, the study found that patients taking fentanyl were three times more likely to experience breathing problems. Fentanyl also presented an 85% higher risk of respiratory depression compared to morphine. The research indicated that individuals using more than one opioid concurrently had a threefold increased risk of this fatal complication. Oxycodone and morphine were also associated with a significantly higher risk of breathing issues when compared to codeine.
Fentanyl's heightened risk is attributed to its potency and rapid entry into the brain, which can quickly suppress breathing. The study also highlighted that patients with chronic obstructive pulmonary disease (COPD) may be particularly vulnerable. Among this group, fentanyl was linked to approximately four times the risk of breathing problems compared to codeine.
The study also noted that higher doses of opioids, even moderate ones (31–60 MME per day), were associated with increased risk. Combining opioids with gabapentinoids, such as gabapentin or pregabalin, further elevated the risk of respiratory depression.
These findings emerge against a backdrop of growing concerns about opioid dependence. In the UK, opioid prescriptions have doubled over the past 25 years, driven partly by a rise in addiction. Opioids, including morphine, codeine, and tramadol, are frequently prescribed for severe acute pain following surgery or injury, and for cancer-related pain. They are also commonly used as anesthetics during surgical procedures.
While opioids remain crucial for managing severe acute pain, the study underscores that the risks are not uniform across all opioid medications or dosages. The research also noted that an estimated 82,000 to 90,000 patients annually overdose on paracetamol, which can lead to liver failure, presenting a different set of health risks.