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An Experimental Paradigm for the Prediction of Post-Operative Pain PPOP
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CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial.

Larisa H Cavallari1,2, Rachel A Myers3, Hrishikesh Chakraborty4

  • 1Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville.

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|February 20, 2026
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Summary
This summary is machine-generated.

Genetic testing for CYP2D6 metabolism guided opioid prescribing, but did not improve postoperative pain control in poor or intermediate metabolizers. This study suggests CYP2D6-guided therapy is not beneficial for managing surgical pain with current multimodal approaches.

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Area of Science:

  • Pharmacogenomics
  • Pain Management
  • Clinical Trials

Background:

  • Genetic variations in cytochrome P450 2D6 (CYP2D6) affect the metabolism of codeine, tramadol, and hydrocodone.
  • Poor or intermediate CYP2D6 metabolizers have reduced conversion to active opioid metabolites, increasing the risk of inadequate pain relief.
  • Personalized prescribing based on CYP2D6 genotype could optimize postoperative pain management.

Purpose of the Study:

  • To evaluate the impact of CYP2D6-guided opioid prescribing on postoperative pain and opioid consumption.
  • To compare pain control and opioid use between patients receiving CYP2D6-guided care and those receiving standard pain management.

Main Methods:

  • An open-label, randomized clinical trial involving 1602 participants undergoing surgery.
  • Participants with poor or intermediate CYP2D6 metabolizer phenotypes (n=351) were randomized to either CYP2D6-guided prescribing or usual care.
  • The primary outcome was the 10-day Silverman integrated analgesic assessment (SIA) score, measuring pain and opioid use.

Main Results:

  • The CYP2D6-guided arm showed higher concordance between prescribed opioids and CYP2D6 phenotype (64% vs. 27%).
  • No significant differences were observed in the primary outcome (SIA score) between the CYP2D6-guided and control arms (2.8; 95% CI, -18.3 to 23.8; P=.80).
  • Secondary outcomes, including pain intensity ratings and overall opioid use (MME/d), also did not differ between the groups.

Conclusions:

  • Despite significant changes in prescribing patterns for CYP2D6 poor and intermediate metabolizers, CYP2D6-guided opioid therapy did not improve postoperative pain control.
  • The findings do not support the use of CYP2D6-guided opioid therapy in the context of contemporary multimodal pain management strategies.
  • Further research may be needed to explore alternative pharmacogenomic approaches or refine strategies for specific patient populations.