JAMA Netw Open

Reduced CYP2D6 activity linked to more ED visits during opioid therapy

July 30, 2025

Study details: This retrospective cohort study used data from the All of Us Research Program to evaluate >31,000 adults (mean age, 51 years; 67% women) prescribed CYP2D6-metabolized opioids (hydrocodone, tramadol, codeine, or oxycodone) for >7 days between 2014 and 2022. CYP2D6 phenotype was determined by genotype and/or CYP2D6 inhibitor use. Primary outcome: pain-related ED visits within 60 days of opioid initiation.

Results: Patients with reduced CYP2D6 activity (phenotypic poor or intermediate metabolizers) had a higher rate of ED visits compared with those with normal or ultrarapid metabolism (2.1% vs. 1.8%; odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06–1.33). Among genotypic normal metabolizers, those also prescribed CYP2D6 inhibitors had significantly more ED visits (OR, 1.49; 95% CI 1.32–1.68). Genotype effects were most pronounced for hydrocodone, tramadol, and codeine.

Clinical impact: These findings support integrating CYP2D6 genotype and drug interaction data into opioid prescribing decisions. Personalized pain management strategies may help reduce avoidable ED visits and improve outcomes for patients receiving CYP2D6-metabolized opioids.

Source:

Nahid NA, et al. (2025, July 1). JAMA Netw Open. CYP2D6 Phenotypes and Emergency Department Visits Among Patients Receiving Opioid Treatment. https://pubmed.ncbi.nlm.nih.gov/40720122/