Potential role for pharmacogenomic testing in combating opioid epidemic

Potential role for pharmacogenomic testing in combating opioid epidemic

Anna K Hanson, PharmD, Essentia Health

Background: The Centers for Disease Control and Prevention estimates that 130 Americans die each day from an opioid overdose, with a six-fold increase in deaths from 1999 to 2017. In addition to lives lost, the cost of medical management of patients with opioid abuse and addiction is estimated at $29.4 billion each year. Considering the magnitude and continued escalation of the opioid epidemic, it is likely a multi-faceted approach is necessary to address it. Marcalus and Bristow-Marcalus suggest that pharmacogenomic testing is one such avenue to fight the opioid epidemic. 

Evidence: The well-documented metabolic pathway of codeine and morphine offers some insight into the pharmacogenomic variations of patients’ response to opioid therapy for pain. Metabolized by the enzyme cytochrome P450 2D6 (CYP2D6), codeine is altered to its highly active metabolite, morphine. According to Marcalus and Bristow-Marcalus, patients who are ultrarapid or poor metabolizers of codeine are at increased risk of abuse due to the unexpectedly high or low conversion of codeine, respectively. Patients with these phenotypes represent a significant portion of the U.S. population, with 6% being ultrarapid and 12% being poor metabolizers of CYP2D6. Guidelines by the Clinical Pharmacogenomics Implementation Consortium (CPIC) describe codeine prescribing recommendations based on metabolism status which could provide guidance for prescribers after pharmacogenomic testing has been performed. According to Crews et al, other opioids such as tramadol, hydrocodone, and oxycodone also undergo metabolism by CYP2D6 and are potentially affected by genetic variants.

Discussion: Marcalus and Bristow-Marcalus suggest the optimal time to assess pharmacogenomics can occur at two points of care: during preoperative screening and at time of referral to a pain specialist. Knowledge of patients’ genetics at these crossroads can help guide treatment to find appropriate therapeutic doses of opioids or direct treatment toward nonopioid pain management. In addition, use of genetic testing may facilitate an open discussion concerning the appropriateness of opioid therapy for a given patient and increase patient satisfaction by providing individualized care. As with any new clinical advancement, the implementation of pharmacogenomics is not without obstacles. The use of pharmacogenomics will require education as to the interpretation and application of the new data and present other hurdles involving cost and navigation of third-party reimbursement. The global nature of comprehensive medication management (CMM) provides an excellent avenue for the incorporation of pharmacogenomics to critically evaluate gene-drug interactions and previous opioid history. This integration of pharmacogenomic testing also creates the opportunity for complete medication reviews and a gateway for expansion of broader CMM services.

Conclusion: The implementation of pharmacogenomics in opioid prescribing may be one tool in a multi-faceted approach to combat the opioid epidemic. While not without barriers, the application of pharmacogenomics in this manner may provide a more individualized approach to optimal opioid prescribing, reduce morbidity and mortality related to opioid abuse, and, as discussed by Marcalus and Bristow-Marcalus, could provide annual cost savings up to $14,000 per patient. CMM pharmacists are uniquely positioned to provide pharmacogenomic consulting services that will have an impact on patients at risk of opioid addiction and abuse.


  1. Marcalus SJ, Bristow-Marcalus S. Combating opioid addiction and abuse - 2 ways to effectively intervene in the cycle of addiction through pharmacogenomics. JAPhA. 2019:59(4):469-473. doi:10.1016/j.japh.2019.04.016.

  2. Centers for Disease Control and Prevention. Opioid overdose: Understanding the epidemic. https://www.cdc.gov/drugoverdose/epidemic/index.html. Updated December 19, 2018. Accessed August 11, 2019.

  3. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012:91(2):321-326. doi:10.1038/clpt.2011.287.