How Pharmacogentic Testing Could Improve the Treatment of Chronic Pain

Although the application of pharmacogenetics in pain management is still fairly new, cardiologists are already widely using genetic testing to make routine treatment decisions when prescribing warfarin and clopidogrel.

The amount of warfarin prescribed needed to properly anticoagulate a patient varies widely from 1 to mg per day, and polymorphisms on two genes — CYP2C9 and VKORC1 — are known to account for as much as 30% to 50% of dosing variability.

Performing genetic testing for mutant alleles on these two genes can help clinicians determine optimal warfarin dosing to avoid under anticoagulation, which can result in delays to needed treatment, or over anticoagulation, which can lead to an increased risk for and adverse bleeding event.

For the anticlotting drug clopidogrel, patients who carry mutations on the CYP2C19 gene are known to have reduced levels of the active drug ingredient, which can result in a lack of treatment efficacy.

In terms of the application of pharmacogenomics in pain management, there is strong evidence linking genetic variability on the CYP2D6 and CYP3A4 genes to oxycodone treatment response, including altered biotransformation of oxydcodone into oxymorphone and genetic effects on the overall clearance of oxycodone and oxymorphone. However, there have been no randomized clinical trials to examine the benefits of genetic testing prior to oxycodone therapy.

In the future pharmacogenetic testing may help pain management clinicians predict medication outcomes, better identify risk for medication interactions, reduce the need for sequential opioid trials, and provide rationale for higher than expected doses, according to Dr. Gupta.

“Billions of dollars are spent each month when doctors try different medications for the same patient,” said Dr. Gupta. “We can do better in prescribing more effective medications quickly and perhaps pharmacogenetics testing can help guide us.”

Dr. Gupta said more studies on pharmacogenetic testing are needed to answer questions about testing reliability and whether health care providers are prepared to use information obtained from such tests in clinical practice. Other areas that may influence how pharmacogenetic testing is received in clinical practice that may important policy implications include insurance reimbursement, and issues around patient privacy and discrimination.

Disclosure: Dr. Gupta receives consulting fees from Millenium Labs.

References

1. Gupta A. “Can Pharmacogenetic Testing Improve the Treatment of Chronic Pain?” Presented at: AAPM 2015. Sept. 17-20; National Harbor, Maryland.

2. Argoff CE. Clinical implications of opioid pharmacogenomics. Clin J Pain. 2010;26(1):S16-S20.

3. Belle DJ, Singh H. Genetic factors in drug metabolism. Am Fam Physician. 2008;77(11):1553-1560.

4. Pharmacogenomic considerations in opioid analgesia. Vuilleumier PH, Stamer UM, Landau R. Pharmgenomics Pers Med. 2012;5:73-87.