Cross-trial prediction of treatment outcome in depression: A machine learning approach

Background: Antidepressant treatment efficacy is low, but might be improved by matching patients to interventions. At present, clinicians have no empirically validated mechanisms to assess whether a patient with depression will respond to a specific antidepressant. We aimed to develop an algorithm to assess whether patients will achieve symptomatic remission from a 12-week course of citalopram. Methods: We used patient-reported data from patients with depression (n=4041, with 1949 completers) from level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D; ClinicalTrials.gov, number NCT00021528) to identify variables that were most predictive of treatment outcome, and used these variables to train a machine-learning model to predict clinical remission. We externally validated the model in the escitalopram treatment group (n=151) of an independent clinical trial (Combining Medications to Enhance Depression Outcomes [COMED]; ClinicalTrials.gov, number NCT00590863). Findings: We identified 25 variables that were most predictive of treatment outcome from 164 patient-reportable variables, and used these to train the model. The model was internally cross-validated, and predicted outcomes in the STAR*D cohort with accuracy significantly above chance (64·6% [SD 3·2]; p<0·0001). The model was externally validated in the escitalopram treatment group (N=151) of COMED (accuracy 59·6%, p=0.043). The model also performed significantly above chance in a combined escitalopram-buproprion treatment group in COMED (n=134; accuracy 59·7%, p=0·023), but not in a combined venlafaxine-mirtazapine group (n=140; accuracy 51·4%, p=0·53), suggesting specificity of the model to underlying mechanisms. Interpretation: Building statistical models by mining existing clinical trial data can enable prospective identification of patients who are likely to respond to a specific antidepressant.