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CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial.


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.

PROVIDER: S-EPMC6650382 | BioStudies |

REPOSITORIES: biostudies

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