The researchers, from McGill University in Canada, have published their results in the American Journal of Public Health.
According to the team, the US and Canada rank number 1 and number 2 in per capita opioid consumption, respectively.
And in 2010 in the US alone, prescribed painkillers were involved in over 16,000 deaths.
Such drugs cause sedation and slow down a person's breathing, but because individuals who are abusing prescription painkillers commonly take larger doses to feel the euphoric effect, their breathing can slow down so much that it stops, resulting in an overdose.
The Centers for Disease Control and Prevention (CDC) state that in 2010, over 12 million people reported using prescription painkillers without a prescription or for the feeling they cause.
Around half of all deaths due to opioids involve at least one other drug, say the CDC. This includes benzodiazepines, cocaine and heroin, as well as alcohol.
Nicholas King, study author from the Biomedical Ethics Unit in the Faculty of Medicine at McGill, says:
"Prescription painkiller overdoses have received a lot of attention in editorials and the popular press, but we wanted to find out what solid evidence is out there."
To investigate, he and his team carried out a systematic review of existing literature, including only reports with quantitative evidence of determinants leading to increased opioid-related mortality in both the US and Canada between 1990-2013.
Prof. King explains that he and his team also "wanted to find out why thousands of people in the US and Canada are dying from prescription painkillers every year, and why these rates have climbed steadily during the past 2 decades."
From their research, the team identified 17 determinants of increasing opioid-related mortality that they classified into three categories: prescriber behavior, user behavior and characteristics, and environmental and systemic determinants.
Prof. King explains that the main determinants were:
"We found little evidence that Internet sales of pharmaceuticals and errors by doctors and patients - factors commonly cited in the media - have played a significant role," he adds.
Though their findings are significant, the researchers say the determinants work independently but "interact in complex ways that vary according to geography and population," which means it is not advisable to make generalizations from single studies.
Additionally, they note that most of the studies in their review were ecological or observational and lacked control groups or adjustment for confounding factors.
As such, the team says preventing prescription painkiller-related deaths will probably require interventions that address numerous determinants and focus on specific locations and populations.
Still, Prof. King says their findings point to an epidemic that physicians, users, the health care system and the environment all play a role in:
"Our work provides a reliable summary of the possible causes of the epidemic of opioid overdoses, which should be useful for clinicians and policy makers in North America in figuring out what further research needs to be done, and what strategies might or might not be useful in reducing future mortality."
"And as efforts are made to increase access to prescription opioids outside of North America," he adds, "our findings might be useful in preventing other countries from following the same path as the US and Canada."
Medical News Today recently reported on a study that suggested moderate doses of the drug MDMA are fatal in warm environments.
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