By Pat Anson, Editor

People who take opioid medication for chronic pain are far more likely to die prematurely from cardiovascular and respiratory problems than they are from accidental overdoses, according to researchers at Vanderbilt University.

Their study, published in JAMA, suggests that many opioid related deaths have been misclassified as overdoses and that public health policy should be more focused on the risks of opioids causing cardiovascular problems.

Researchers looked at a database of nearly 23,000 Medicaid patients in Tennessee who were prescribed either opioids; anti-seizure nerve medications such as pregabalin (Lyrica) and gabapentin (Neurontin); or a low dose antidepressant for chronic non-cancer pain.  

After four months, there were 185 deaths in the opioid group, a mortality rate that that was 1.6 times greater than the patients taking anti-seizure drugs or antidepressants. More than two-thirds of the excess deaths were due to causes other than accidental overdose.

Over twice as many patients died from cardiovascular and respiratory problems (89) than from overdoses (34).

“The increased risk of cardiovascular death could be related to adverse respiratory effects of long-acting opioids. Opioids can cause or exacerbate sleep-disordered breathing, including both obstructive and central sleep apnea,” wrote lead author Wayne Ray, PhD, of the Vanderbilt University School of Medicine.

“More than two-thirds of the excess deaths for patients in the long-acting opioid group were not coded as being due to unintentional overdose. If there is this degree of misclassification, then previous research on opioid mortality, most of which has focused on overdose deaths identified from death certificates, has substantially underestimated the true risks of opioids.”

The Centers for Disease Control and Prevention uses death certificate codes in its reports on mortality. The agency estimates that nearly 19,000 Americans died from overdoses of prescription pain medication in 2014. However, CDC researchers admit some of the overdoses may have been counted twice, and that some overdoses from illicit opioids such as heroin and fentanyl may have been counted as prescription drug deaths.

One weakness of the Vanderbilt study is that it only looked at mortality rates in the first few months of treatment and did not include deaths from long-term medication use.

“The study finding that prescription of long acting opioids was associated with increased cardiovascular and other non-overdose mortality adds to the already considerable known harms of the opioids and thus should be considered when assessing the benefits and harms of medications for chronic pain,” Ray wrote. “Nevertheless, for some individual patients, the therapeutic benefits from long-acting opioid therapy may outweigh the modest increase in mortality risk.”

The mortality rate for chronic pain patients who died in a hospital was higher for patients given antidepressants and anti-seizure drugs than it was for opioids.