Differential Treatment Benet Prediction for Treatment Selection in Depression: A Deep Learning Analysis of STAR*D and CO-MED Data

Abstract

Depression affects one in nine people, but treatment response rates remain low. There is significant potential in the use of computational modeling techniques to predict individual patient responses and thus provide more personalized treatment. Deep learning is a promising computational technique that can be used for differential treatment selection based on predicted remission probability. Using Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and Combining Medications to Enhance Depression Outcomes (CO-MED) trial data, we employed deep neural networks to predict remission after feature selection. Treatments included were citalopram, escitalopram, bupropion SR plus escitalopram, and venlafaxine plus mirtazapine. Differential treatment benefit was estimated in terms of improvement of population remission rates after application of the model for treatment selection using two approaches: (1) using predictions generated directly from the model (the predicted improvement approach) and (2) using bootstrapping for sample generation and then estimating population remission rate for patients who actually received the drug predicted by the model compared to the general population (the actual improvement approach). Our deep learning model predicted remission in a pooled CO-MED/STAR*D dataset (including four treatments) with an area under the curve of 0.69 using 17 input features. Our actual improvement analysis showed a statistically significant 2.48% absolute improvement (corresponding to a 7.2% relative improvement) in population remission rate ( p = 0.01, CI 2.48% ± 0.5%). Our model serves as proof-of-concept that deep learning approaches, with further refinement and work to address concerns about differences between studies when multiple datasets are used for training, may have utility in differential prediction of antidepressant response when selecting from a number of treatment options.