Key features associated with opioid misuse in chronic pain: A machine learning cross-sectional study

Abstract Importance Opioid misuse remains a critical public health concern, associated with increased risk of overdose, psychiatric comorbidity, and societal costs. While machine learning (ML) analyses have been used to identify features associated with opioid misuse across various clinical settings, few studies have examined both modifiable and non-modifiable features. Understanding modifiable features may inform targeted prevention and intervention strategies to reduce opioid misuse. Objective To identify key features associated with opioid misuse severity in patients with chronic pain taking long-term prescription opioids. Design, Setting, and Participants This analysis used data from clinical trials investigating a skills-based pain management intervention. Participants were 314 community-dwelling adults with chronic pain who were taking daily opioid medications (≥ 10 morphine-equivalent daily dose) for at least 3 months. Data was extracted from baseline assessments. Outcomes and Measures Opioid misuse severity was assessed using the Current Opioid Misuse Measure (COMM). Thirty-six demographic and clinical features were evaluated, including PROMIS symptom domains (e.g., pain rating, pain interference, physical function, fatigue, sleep disturbance, depression, anxiety, and anger) as well as emotional ambivalence, pain catastrophizing, trauma exposure, and substance use. Results Among the seven ML algorithms (Random Forest, XGBoost, Support Vector Regression, LASSO regression, Ridge Regression, Elastic Net, and Multilayer Perceptron), the Elastic Net model demonstrated the strongest performance, yielding the highest correlation with COMM scores (mean r = 0.61, 95% CI [0.40, 0.73]) and the lowest root mean square error (mean RMSE = 4.16, 95% CI [3.41, 4.80]). Feature ablation analysis identified anger (Δr = 0.053), emotional ambivalence (Δr = 0.022), pain catastrophizing (Δr = 0.008), and fatigue (Δr = 0.002) as the most influential features associated with the COMM scores. Shapley Additive exPlanations (SHAP) analysis confirmed that higher levels of these key features were associated with higher COMM scores. Conclusions and Relevance Emotional factors, particularly anger, emerged as key features associated with the severity of opioid misuse. These findings suggest that interventions targeting emotion regulation, especially anger management, may reduce opioid misuse among individuals receiving long-term opioid therapy for chronic pain.