JAMA Netw Open

Pharmacogenetic testing for opioid selection fails to improve postop pain control in randomized trial

March 3, 2026

A multicenter randomized trial of 351 surgical patients with CYP2D6 poor or intermediate metabolizer phenotypes found that genotype-guided opioid prescribing—avoiding hydrocodone, tramadol, and codeine in favor of alternatives—didn't improve pain control or reduce opioid consumption compared with usual care. Genotype-guided care significantly increased concordance between CYP2D6 phenotype and opioid choice (64% vs. 27%; p<0.001) but didn't improve a 10-day composite pain-and-opioid-use outcome (Silverman integrated analgesic assessment) or reduce pain scores or daily opioid use.

The findings contrast with earlier single-center data and suggest that in contemporary practice—where multimodal analgesia is standard—CYP2D6 genotyping may not provide additional benefit for post-op pain management. The authors note that widespread use of non-opioid analgesics may have diminished the potential impact of genotype-guided opioid selection.

In an invited commentary, Dr. Andrew Monte of the University of Colorado argues these negative results reflect the complexity of pain management, which depends on multiple factors beyond single genetic variants—including surgical technique, multimodal analgesia, psychological factors, and social determinants of health.

Clinical takeaway: Current evidence doesn't support routine CYP2D6 pharmacogenetic testing for post-op opioid selection in patients receiving multimodal pain management.

Source:

Cavallari L, et al. (2026, February 20). JAMA Netw Open. CYP2D6-Guided Opioid Management and Postoperative Pain Control: a randomized clinical trial. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2845325

Monte, A. (2026, February 20). JAMA Netw Open. Complexity of Pharmacologic Pain Control—The Allegory of the Pharmacogenetic Cave. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2845327