Health Care Providers Could Prevent Opioid-Related Deaths by Testing for Certain Genes, Scientists Claim

Investigators unravel pharmacogenetic effects on opioid analgesia

A review published in Clinical Chemistry has identified 10 genes that show promise in predicting how patients will respond to opioid pain medications. Using these genetic markers, health care providers could potentially tailor opioid therapy better to curb the skyrocketing rate of deaths from these drugs, the authors claim.

More than 17,500 Americans died in 2015 from prescription opioid overdoses, which is more than four times the number of people who died from this cause in 1999, according to the article. But it is not just abuse of these medications that can lead to overdoses. Even in patients with severe pain and a legitimate need for opioids, the dose required to alleviate pain varies widely among individuals. This means that clinicians must essentially use a trial-and-error strategy to determine the correct type of opioid and the dosage that will help a patient. This approach puts some patients at increased risk of life-threatening adverse effects, such as respiratory depression, while leaving other patients undertreated and in pain, according to the authors.

To date, researchers have identified numerous genes that could potentially guide opioid treatment to make it more precise and safe. Despite these advances, the medical community has only developed treatment guidelines based on one of these genes (CYP2D6) and has not determined which of the other genes should be used in practice, the authors point out.

To identify the genes that could affect patient care the most, a team of researchers at the Erasmus University Medical Center in Rotterdam, the Netherlands, reviewed 4,257 studies on opioid genetics. The researchers assessed the utility of each gene studied based on whether 1) several independent investigations confirmed the gene’s effect on patients’ opioid response, and 2) the gene’s frequency in the white population was high enough for use in screening tests. Using these criteria, the team identified 10 genes that showed the highest potential for refining the way opioids are prescribed and that health care providers should implement clinically. In addition to CYP2D6, the most notable of these genes include SLC22A1, the OPRM1 variant 118A>G, and COMT.

Research has shown that the presence of two inactive SLC22A1 genes leads to high blood concentrations of tramadol’s active metabolite and, in children, significantly lowers the clearance of morphine. This means that patients with these genetic mutations might be at increased risk of overdosing from tramadol and morphine, particularly if they also have certain CYP2D6 mutations. Conversely, studies have demonstrated that patients with the OPRM1 118A>G variant require higher doses of opioids but have a lower risk of adverse events. Finally, certain COMT mutations are associated with both lower opioid requirements and fewer adverse effects, while still other COMT mutations have been linked with the highest pain scores and opioid consumption in patients who have undergone surgery.

“The most solid evidence of a clinically relevant pharmacogenetic effect on analgesic treatment with opioids is available for genetic variations in CYP2D6, COMT, [and] SLC22A1, and the genetic variant OPRM1 118A>G,” said study leader Ron H.N. van Schaik, PhD. “As clinical guidelines for codeine and CYP2D6 genotyping have been formulated and CYP2D6 genotyping has been successfully implemented in pediatric clinical practice … the application of pharmacogenetics in the management of pain with opioids certainly has the potential to improve therapy.”

Source: PR Newswire; June 22, 2017.