CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice

Pharmacogenomics J. 2021 Aug;21(4):484-490. doi: 10.1038/s41397-021-00226-8. Epub 2021 Mar 9.


Cytochrome P450 2D6 (CYP2D6) O-demethylates codeine to the active drug, morphine. However, the utility of testing for CYP2D6 metabolizer status in patients receiving codeine in real-world clinical practice is poorly defined. Using data from a DNA bank linked to de-identified electronic health records, we studied 157 patients with a baseline pain score higher than 4 (0-10 scale) who received codeine. Based on CYP2D6 genotyping, 69 were classified as poor/intermediate and 88 as normal/ultrarapid CYP2D6 metabolizers. Pain response was defined as a score of 4 or lower while receiving codeine. In a propensity-score adjusted model, poor/intermediate metabolizers had lower odds (OR = 0.35, p = 0.02) of achieving a pain response than normal/ultrarapid metabolizers. To discriminate between codeine responders and nonresponders, a score including CYP2D6 phenotype and clinical variables was built. The response rate was 38.5% among patients in the high, 17.3% in the intermediate, and 9.4% in the low-score groups, respectively (p = 0.001).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Analgesics, Opioid / therapeutic use*
  • Codeine / therapeutic use*
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Morphine / therapeutic use
  • Phenotype
  • Polymorphism, Genetic / genetics


  • Analgesics, Opioid
  • Morphine
  • Cytochrome P-450 CYP2D6
  • Codeine