Genotype-Guided Opioid Therapy in Patients Undergoing Lumbar Spine Surgery Results in Lower Rates of Delirium and Superior Pain Control: A Single Institutional Feasibility Study

Introduction: Despite the use of multimodal therapies and widespread adoption of Enhanced Recovery Protocols, 33% - 50% of patients report poor pain control after spine surgery. The CYP2D6 enzyme metabolizes opioids commonly prescribed for spine-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. Thus, while some patients achieve the desired therapeutic response from their drug therapy, others do not; and a subset of patients will experience adverse effects, which can range from bothersome to life threatening.

Methods: Adult patients undergoing lumbar spine surgery were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient-reported pain and symptom scores at baseline and up to 12 weeks, were assessed.

Results: Most (24/25, 96%) patients approached for the study agreed to participate. Of the 24 patients randomized (48% female), 15 were randomized to the genotype guided arm and the rest standard of care. Normal metabolizers were prescribed tramadol for pain control, while intermediate and poor metabolizers were prescribed non-CYP2D6 opioids such as morphine or hydromorphone. At baseline, there were no differences in VAS back pain (p=0.76), VAS leg pain (0.51) and ODI(p=0.60) and EQ-5D(p=0.40) between the genotype-guided and non-genotype cohorts. Post-operatively, patients randomized to the genotype-guided opioid arm reported significantly lower VAS back pain (p=0.04), VAS leg pain (0.03) and ODI(p=0.02) scores compared to those in the standard of care arm. Rates of post-operative delirium was 2-fold lower in the genotype-guided cohort. The majority of patients in the genotype-guided opioid cohort (70%) were discharged directly to home, with only a minority discharged to a rehabilitation facility or nursing home.

Conclusion : In this single institutional RCT, a genotype-guided opioid prescribing strategy was associated with lower rates of post-operative delirium, superior pain control and improvement in functional disability. Furthermore, our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with spine-related pain.