The potential of CYP2D6 phenotyping to improve opioid dosing strategies

Abstract

Background: Prescription opioids account for more than 40% of opioid induced mortalities. With the trend towards increased opioid prescribing set to continue rising, opioid-based adverse drug reactions, (ADRs) and their associated human and financial cost present a major global public health concern. The review examined the relationship between CYP2D6 phenotypes and opioid metabolising. The aim was to establish whether screening for CYP2D6 phenotypes would improve existing opioid dosing strategies and reduce ADRs. Method: A systematic review was conducted using the online Web of Science database. Selected key words and Boolean operator combinations were used to search the relevant literature. Identified studies were screened against pre-defined inclusion/exclusion criteria. Eligible studies were subject to full review and quality assessment. A narrative analysis was performed to synthesise data from the studies included in the final review. Results: The review yielded five studies that met the eligibility criteria and were subject to full review. Four of the five studies reported significant effects of CYP2D6 phenotypes on opioid metabolising or opioid based ADRs. Three studies focused exclusively on pharmacokinetics, two studies focused exclusively on ADRs, and one study considered pharmacokinetics and ADRs. All pharmacokinetic studies reported a significant association between CYP2D6 phenotypes and opioid metabolising. Only one of the studies reported a significant association between CYP2D6 phenotypes and ADRs. Conclusion: The majority of evidence considered in the review supports the role of CYP2D6 in the metabolising of opioids and opioid based ADRs. Consequently, CYP2D6 screening should be considered as a potential mechanism for improving existing opioid dosing strategies and reducing ADRs. There is a need for further higher quality primary data studies focusing specifically on CYP2D6 phenotyping in the context of dosage strategies and exploring impact in longitudinal designs. Future studies should also seek to develop cost effective CYP2D6 screening methods to help support the clinical significance of CYP2D6 phenotyping.