Clinical prediction of opioid use disorder in chronic pain patients: a cohort-retrospective study with a pharmacogenetic approach

Minerva Anestesiol. 2024 May;90(5):386-396. doi: 10.23736/S0375-9393.24.17864-9. Epub 2024 Apr 12.


Background: Opioids are widely used in chronic non-cancer pain (CNCP) management. However, they remain controversial due to serious risk of causing opioid use disorder (OUD). Our main aim was to develop a predictive model for future clinical translation that include pharmacogenetic markers.

Methods: An observational study was conducted in 806 pre-screened Spanish CNCP patients, under long-term use of opioids, to compare cases (with OUD, N.=137) with controls (without OUD, N.=669). Mu-opioid receptor 1 (OPRM1, A118G, rs1799971) and catechol-O-methyltransferase (COMT, G472A, rs4680) genetic variants plus cytochrome P450 2D6 (CYP2D6) liver enzyme phenotypes were analyzed. Socio-demographic, clinical and pharmacological outcomes were also registered. A logistic regression model was performed. The model performance and diagnostic accuracy were calculated.

Results: OPRM1-AA genotype and CYP2D6 poor and ultrarapid metabolizers together with three other potential predictors: 1) age; 2) work disability; 3) oral morphine equivalent daily dose (MEDD), were selected with a satisfactory diagnostic accuracy (sensitivity: 0.82 and specificity: 0.85), goodness of fit (P=0.87) and discrimination (0.89). Cases were ten-year younger with lower incomes, more sleep disturbances, benzodiazepines use, and history of substance use disorder in front of controls.

Conclusions: Functional polymorphisms related to OPRM1 variant and CYP2D6 phenotypes may predict a higher OUD risk. Established risk factors such as young age, elevated MEDD and lower incomes were identified. A predictive model is expected to be implemented in clinical setting among CNCP patients under long-term opioids use.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Catechol O-Methyltransferase / genetics
  • Chronic Pain* / drug therapy
  • Chronic Pain* / genetics
  • Cohort Studies
  • Cytochrome P-450 CYP2D6 / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Opioid-Related Disorders* / genetics
  • Pharmacogenetics
  • Receptors, Opioid, mu / genetics
  • Retrospective Studies


  • OPRM1 protein, human