CYP2D6 Metabolizer Phenotype and New Persistent Opioid Use After Spine Surgery.

CYP2D6

CYP2D6 metabolizer phenotype (poor, intermediate, normal, ultrarapid) modulates exposure to opioids prescribed after surgery.

This retrospective cohort from the All of Us Research Program studied 3,820 opioid-naive adults with whole-genome sequencing who underwent spine fusion or decompression. New persistent opioid use occurred in 460 patients (12.0%). The overall association with CYP2D6 phenotype was significant (χ2 = 15.30; P = .002). Versus normal metabolizers, adjusted odds ratios were 1.48 (95% CI 1.00-2.18) for poor, 1.05 (0.85-1.30) for intermediate and 1.50 (0.89-2.54) for ultrarapid metabolizers; in poor metabolizers receiving hydrocodone it reached 2.15 (1.07-4.32). Extreme-phenotype estimates were reportable only in participants of European ancestry.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The signal is modest, confidence intervals at the extremes touch or include 1, and the biology is not obvious since risk rises at both extremes. The authors themselves conclude that drug-specific replication in more diverse cohorts is needed before any implementation: one to watch, without changing practice.

Analysis by Dr Thibaut Benquey