Refining Prediction in Treatment-Resistant Depression: Results of Machine Learning Analyses in the TRD III Sample

Objective: The study objective was to generate a prediction model for treatment-resistant depression (TRD) using machine learning featuring a large set of 47 clinical and sociodemographic predictors of treatment outcome. Method: 552 Patients diagnosed with major depressive disorder (MDD) according to DSM-IV criteria were enrolled between 2011 and 2016. TRD was defined as failure to reach response to antidepressant treatment, characterized by a Montgomery-Asberg Depression Rating Scale (MADRS) score below 22 after at least 2 antidepressant trials of adequate length and dosage were administered. RandomForest (RF) was used for predicting treatment outcome phenotypes in a 10-fold cross-validation. Results: The full model with 47 predictors yielded an accuracy of 75.0%. When the number of predictors was reduced to 15, accuracies between 67.6% and 71.0% were attained for different test sets. The most informative predictors of treatment outcome were baseline MADRS score for the current episode; impairment of family, social, and work life; the timespan between first and last depressive episode; severity; suicidal risk; age; body mass index; and the number of lifetime depressive episodes as well as lifetime duration of hospitalization. Conclusions: With the application of the machine learning algorithm RF, an efficient prediction model with an accuracy of 75.0% for forecasting treatment outcome could be generated, thus surpassing the predictive capabilities of clinical evaluation. We also supply a simplified algorithm of 15 easily collected clinical and sociodemographic predictors that can be obtained within approximately 10 minutes, which reached an accuracy of 70.6%. Thus, we are confident that our model will be validated within other samples to advance an accurate prediction model fit for clinical usage in TRD.