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ABSTRACT: Purpose
CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.Methods
Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 inhibitor use, with recommendations for opioid prescribing made in the CYP2D6-guided arm. Pain was assessed at baseline and 3 months using PROMIS® measures.Results
On stepwise multiple linear regression, the primary outcome of composite pain intensity (composite of current pain and worst and average pain in the past week) among IM/PMs initially prescribed tramadol/codeine (n = 45) had greater improvement in the CYP2D6-guided versus usual care arm (-1.01 ± 1.59 vs. -0.40 ± 1.20; adj P = 0.016); 24% of CYP2D6-guided versus 0% of usual care participants reported ≥30% (clinically meaningful) reduction in the composite outcome. In contrast, among normal metabolizers prescribed tramadol or codeine at baseline, there was no difference in the change in composite pain intensity at 3 months between CYP2D6-guided (-0.61 ± 1.39) and usual care (-0.54 ± 1.69) groups (adj P = 0.540).Conclusion
These data support the potential benefits of CYP2D6-guided pain management.
SUBMITTER: Smith DM
PROVIDER: S-EPMC6650382 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Smith D Max DM Weitzel Kristin W KW Elsey Amanda R AR Langaee Taimour T Gong Yan Y Wake Dyson T DT Duong Benjamin Q BQ Hagen Melanie M Harle Christopher A CA Mercado Elvira E Nagoshi Ying Y Newsom Kimberly K Wright Ashleigh A Rosenberg Eric I EI Starostik Petr P Clare-Salzler Michael J MJ Schmidt Siegfried O SO Fillingim Roger B RB Johnson Julie A JA Cavallari Larisa H LH
Genetics in medicine : official journal of the American College of Medical Genetics 20190123 8
<h4>Purpose</h4>CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.<h4>Methods</h4>Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 ...[more]