Using a machine learning approach to investigate factors associated with treatment-resistant depression among adults with chronic non-cancer pain conditions and major depressive disorder

Objective: Presence of chronic non-cancer pain conditions (CNPC) among adults with major depressive disorder (MDD) may reduce benefits of antidepressant therapy, thereby increasing the possibility of treatment resistance. This study sought to investigate factors associated with treatment-resistant depression (TRD) among adults with MDD and CNPC using machine learning approaches. Methods: This retrospective cohort study was conducted using a US claims database which included adults with newly diagnosed MDD and CNPC (January 2007–June 2017). TRD was identified using a clinical staging algorithm for claims data. Random forest (RF), a machine learning method, and logistic regression was used to identify factors associated with TRD. Initial model development included 42 known and/or probable factors that may be associated with TRD. The final refined model included 20 factors. Results: Included in the sample were 23,645 patients (73% female mean age: 55 years; 78% with ≥2 CNPC, and 91% with joint pain/arthritis). Overall, 11.4% adults (N = 2684) met selected criteria for TRD. The five leading factors associated with TRD were the following: mental health specialist visits, polypharmacy (≥5 medications), psychotherapy use, anxiety, and age. Cross-validated logistic regression model indicated that those with TRD were younger, more likely to have anxiety, mental health specialist visits, polypharmacy, and psychotherapy use with adjusted odds ratios (AORs) ranging from 1.93 to 1.27 (all ps <.001). Conclusion: Machine learning identified several factors that warrant further investigation and may serve as potential targets for clinical intervention to improve treatment outcomes in patients with TRD and CNPC.